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CORK Bibliography: Craving and Drugs

70 citations. January 2011 to present

Prepared: March 2012

Back SE; Payne RL; Wahlquist AH; Carter RE; Stroud Z; Haynes L et al. Comparative profiles of men and women with opioid dependence: Results from a national multisite effectiveness trial. American Journal of Drug and Alcohol Abuse 37(5): 313-323, 2011. (51 refs.)

Background: Accumulating evidence indicates important gender differences in substance use disorders. Little is known, however, about gender differences and opioid use disorders. Objectives: To compare demographic characteristics, substance use severity, and other associated areas of functioning (as measured by the Addiction Severity Index-Lite (ASI-Lite)) among opioid-dependent men and women participating in a multisite effectiveness trial. Methods: Participants were 892 adults screened for the National Institute on Drug Abuse Clinical Trials Network investigation of the effectiveness of two buprenorphine tapering schedules. Results: The majority of men and women tested positive for oxycodone (68% and 65%, respectively) and morphine (89% each). More women than men tested positive for amphetamines (4% vs. 1%, p < .01), methamphetamine (11% vs. 4%, p < .01), and phencyclidine (8% vs. 4%, p = .02). More men than women tested positive for methadone (11% vs. 6%, p = .05) and marijuana (22% vs. 15%, p = .03). Craving for opioids was significantly higher among women (p < .01). Men evidenced higher alcohol (p < .01) and legal (p = .04) ASI composite scores, whereas women had higher drug (p < .01), employment (p < .01), family (p < .01), medical (p < .01), and psychiatric (p < .01) ASI composite scores. Women endorsed significantly more current and past medical problems. Conclusions: Important gender differences in the clinical profiles of opioid-dependent individuals were observed with regard to substance use severity, craving, medical conditions, and impairment in associated areas of functioning. The findings enhance understanding of the characteristics of treatment-seeking men and women with opioid dependence, and may be useful in improving identification, prevention, and treatment efforts for this challenging and growing population.

Barrett SP; Campbell ML; Temporale K; Good KBP. The acute effect of Swedish-style snus on cigarette craving and self-administration in male and female smokers. Human Psychopharmacology: Clinical and Experimental 26(1): 58-62, 2011. (18 refs.)

Introduction: Swedish-style snus (SS) has recently garnered controversy for its proposed use as a smoking cessation aid and/or harm reduction tool. However, to date, little work has been done to evaluate the extent to which SS affects cigarette cravings and smoking behavior under double-blind controlled conditions. Methods: During four double-blind placebo-controlled randomized sessions, 15 smokers (8 male) administered SS, placebo (nicotine/tobacco-free) snus (PS), a nicotine-containing lozenge (NL), or a placebo lozenge (PL) for 30 min and assessed their effects using Visual Analogue Scales and the Brief Questionnaire of Smoking Urges. They could then self-administer their usual brand of cigarettes using a progressive ratio task over the next 60 min. Following the completion of their final session, 11 participants (6 male) ranked each of the products used in the study in terms of their preferences. Results: Relative to the other products, SS was associated with a decreased intention to smoke as well as a delayed onset of cigarette smoking in men but not women. However, SS administration was also associated with increased feelings of frustration and irritability relative to NL and SS was ranked as being the least preferred product used in the study. Discussion: Findings suggest that SS is effective in acutely suppressing craving and smoking in at least some smokers, but that its acceptability may be limited.

Bedi G; Preston KL; Epstein DH; Heishman SJ; Marrone GF; Shaham Y et al. Incubation of cue-induced cigarette craving during abstinence in human smokers. Biological Psychiatry 69(7): 708-711, 2011. (20 refs.)

Background: Abstinent drug users remain at risk for relapse long after withdrawal subsides. Animal studies indicate that responses to drug-related cues not only persist but increase with abstinence, a phenomenon termed "incubation of drug craving." It is unknown whether cue-induced craving increases, decreases, or remains constant with abstinence in humans. We investigated effects of abstinence on cue-induced craving in cigarette smokers. Methods: Eighty-six non-treatment-seeking, adult smokers (>= 10 cigarettes daily) were paid to abstain for 7 (Group 1), 14 (Group 2), or 35 (Groups 3 and 4) days. Abstinence was verified daily. Groups 1, 2, and 3 underwent a single cue session on the final abstinence day (7, 14, or 35). Group 4 viewed cues on Days 7, 14, and 35. Results: Between and within groups, smoking-cue-induced craving increased with abstinence on some measures. Cue-induced craving was greater in Group 3 (35-day) compared with Group 1 (7-day). Within Group 4, cue-induced craving was greater at 35 than 14 days. Cue-induced craving did not decrease with abstinence on any measure. Conclusions: We present initial evidence of incubation of cue-induced craving in humans. The observation that cue-induced craving increases with abstinence, even as "background" craving and withdrawal symptoms subside, might have treatment implications.

Berkman ET; Falk EB; Lieberman MD. In the trenches of real-world self-control: Neural correlates of breaking the link between craving and smoking. Psychological Science 22(4): 498-506, 2011. (40 refs.)

Successful goal pursuit involves repeatedly engaging self-control against temptations or distractions that arise along the way. Laboratory studies have identified the brain systems recruited during isolated instances of self-control, and ecological studies have linked self-control capacity to goal outcomes. However, no study has identified the neural systems of everyday self-control during long-term goal pursuit. The present study integrated neuroimaging and experience-sampling methods to investigate the brain systems of successful self-control among smokers attempting to quit. A sample of 27 cigarette smokers completed a go/no-go task during functional magnetic resonance imaging before they attempted to quit smoking and then reported everyday self-control using experience sampling eight times daily for 3 weeks while they attempted to quit. Increased activation in right inferior frontal gyrus, pre-supplementary motor area, and basal ganglia regions of interest during response inhibition at baseline was associated with an attenuated association between cravings and subsequent smoking. These findings support the ecological validity of neurocognitive tasks as indices of everyday response inhibition.

Blum K; Liu YJ; Shriner R; Gold MS. Reward circuitry dopaminergic activation regulates food and drug craving behavior. (review). Current Pharmaceutical Design 17(12): 1158- 1167, 2011. (127 refs.)

Neural circuits implicated in drug conditioning, craving and relapse overlap extensively with those involved in natural reward and reinforcement like food. Exposure to drug-related cues in human addicts results in drug craving and localized activation of central circuits that are known to mediate cue-induced reinstatement of drug-seeking behavior in animal models of relapse. Similar regional activation patterns occur in humans in response to cues associated with foods. Furthermore, drug-and food-related cues not only activate common neuroanatomical regions but also result in similar activity-regulated gene expression programs within these shared areas. Cues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The upregulation of a number of early genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. The dopaminergic, enkephalinergic, and fos gene expressions are important regulatory genetic pathways for food craving behaviors. An umbrella term to describe common genetic antecedents of multiple impulsive, compulsive and addictive behaviors is Reward Deficiency Syndrome (RDS). Individuals possessing a paucity of serotonergic and/or dopaminergic receptors and an increased rate of synaptic dopamine catabolism, due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate dopamine release including alcohol, opiates, psychostimulants, nicotine, glucose, gambling, sex, and even excessive internet gaming, among others. Finally, utilizing the long term dopaminergic activation approach will ultimately lead to a common safe and effective modality to treat RDS behaviors including aberrant food and drug craving behaviors.

Brandon TJ; Drobes DJ; Unrod M; Heckman BW; Oliver JA; Roetzheim RC. et al. Varenicline effects on craving, cue reactivity, and smoking reward. Psychopharmacology 218(2): 391-403, 2011

Varenicline is an alpha4beta2 nicotinic acetylcholine receptor partial agonist that has been found to be effective for treating tobacco dependence. However, the subjective and behavioral mediators of its efficacy are not known. Using multiple sessions of laboratory-based assessment, this double-blind, placebo-controlled experiment was designed to test if varenicline reduced both tonic and cue-provoked tobacco cravings, and if it attenuated perceived reward from smoking. Participants in the present analysis include 100 smokers who were scheduled for three assessment sessions: at baseline, before receiving medication; at mid-run-in, 5-7days after beginning medication; and after full dosage was reached, 12-15days. Following overnight abstinence, each session included assessment of tonic craving, reactivity (including craving) to smoking cues, expected value of a cigarette, smoking behavior, and self-reported reward following smoking. Varenicline, compared to placebo, reduced tonic craving, cue-provoked craving by the final assessment, the expected value of cigarettes, number of puffs and time spent smoking, and self-reported reward (i.e., satisfaction) from smoking. Results showing that varenicline reduced tonic craving levels and perceived reward from smoking are consistent with reports from clinical trials, strengthening the evidence in support of these subjective mechanisms of action. This is the first placebo-controlled study to demonstrate that varenicline reduced cue-provoked cravings, thereby offering another potential mediator of its therapeutic effects. Findings may aid in the development of more targeted interventions for tobacco dependence.

Buckner JD; Crosby RD; Silgado J; Wonderlich SA; Schmidt NB. Immediate antecedents of marijuana use: An analysis from ecological momentary assessment. Journal of Behavior Therapy and Experimental Psychiatry 43(1): 647-655, 2012. (54 refs.)

Background and objectives: Marijuana remains the most commonly used illicit substance. Marijuana craving, anxiety, and peer marijuana use are thought to play important roles in the etiology and maintenance of marijuana use. The present study aimed to identify patterns between marijuana use and these affective and situational risk factors in the natural environment. Methods: The sample consisted of 49 current marijuana users (38.8% female), 63.2% of whom evinced a current cannabis use disorder. Ecological momentary assessment was used to collect multiple daily ratings of marijuana craving, state anxiety, and peer marijuana use over two weeks. Mixed effects linear models were used to examine within- and between-day antecedents, correlates, and consequences of marijuana use. Results: Between-day analyses indicated that marijuana use days were associated with higher marijuana craving but lower state anxiety. Within-day analyses confirmed that marijuana craving was higher prior to marijuana use and lower following use. Anxiety was related to marijuana craving. Although anxiety was somewhat higher prior to marijuana use, it did not decrease significantly following use. The vast majority of marijuana use occurred when others were also using marijuana. Limitations: The sample was comprised of college students, a group at particular risk for marijuana use and use-related problems. Future work is necessary to determine whether results generalize to other populations. Conclusions: These data support the contention that marijuana craving, anxiety, and peer use play important roles in the maintenance of marijuana use.

Buchowski MS; Meade NN; Charboneau E; Park S; Dietrich MS; Cowan RL et al. Aerobic exercise training reduces cannabis craving and use in non-treatment seeking cannabis-dependent adults. PLoS ONE 6(3): article e17465, 2011. (38 refs.)

Background: Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise. Aims: To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions. Design: Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR) monitoring (60-70% HR reserve) over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight. Participants: Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25 +/- 63 years, 8 females) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID). Measurements: Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF). Findings: Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8-10.9). Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9-5.4) and follow-up (4.1 joints, SD = 2.5, range 1.1-9.5) periods were lower than during the run-in period (both P <.005). Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P = .006), emotionality (P = .002), expectancy (P = .002), and purposefulness (P = .002). Conclusions: The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to understanding of the physical and emotional underpinnings of cannabis dependence and recovery from this disorder.

Buckner JD; Zvolensky MJ; Smits JAJ; Norton PJ; Crosby RD; Wonderlich SA et al. Anxiety sensitivity and marijuana use: An analysis from ecological momentary assessment. Depression and Anxiety 28(5): 420- 426, 2011. (41 refs.)

Background: The cognitive factor of Anxiety Sensitivity (AS; the fear of anxiety and related bodily sensations) is theorized to play a role in cannabis use and its disorders. Lower-order facets of AS (physical concerns, mental incapacitation concerns, and social concerns) may be differentially related to cannabis use behavior. However, little is known about the impact of AS facets on the immediate antecedents of cannabis use. Methods: This study used ecological momentary assessment (EMA) to prospectively examine the relations between specific facets of AS, cannabis craving, state anxiety, and cannabis use in the natural environment using real-world data about ad lib cannabis use episodes. Participants were 49 current cannabis users (38.8% female). Results: AS-mental incapacitation fears were related to significantly greater severity of cannabis-related problems at baseline. During the EMA period, AS-mental incapacitation and AS-social concerns significantly interacted with cannabis craving to prospectively predict subsequent cannabis use. Specifically, individuals with higher craving and either higher AS-mental incapacitation or AS-social concerns were the most likely to subsequently use cannabis. In contrast to prediction, no AS facet significantly moderated the relationship between state anxiety and cannabis use. Conclusions: These findings suggest facets of AS (mental incapacitation and social fears) interact with cannabis craving to predict cannabis use. Findings also suggest differential relations between facets of AS and cannabis-related behaviors.

Chandra S; Scharf D; Shiffman S. Within-day temporal patterns of smoking, withdrawal symptoms, and craving. Drug and Alcohol Dependence 117(2-3): 118-125, 2011. (48 refs.)

We examined the temporal relationships between smoking frequency and craving and withdrawal. 351 heavy smokers (>= 15 cigarettes per day) used ecological momentary assessment and electronic diaries to track smoking, craving, negative affect, arousal, restlessness, and attention disturbance in real time over 16 days. The waking day was divided into 82-h "bins" during which cigarette counts and mean levels of craving and withdrawal were computed. Cross-sectional analyses showed no association between restlessness and smoking, and arousal and smoking, but craving (b = 0.65, p < 0.01) was positively associated, and negative affect (b = -0.20, p < 0.01), and attention disturbance (b = -0.24, p < 0.01) were inversely associated with smoking. In prospective lagged analyses, higher craving predicted more subsequent smoking and higher smoking predicted lower craving (p's < 0.01). Higher restlessness also predicted more subsequent smoking and higher smoking predicted lower restlessness (p's < 0.01). Higher negative affect did not predict later smoking, but more smoking preceded lower negative affect (p < 0.01). Neither attention disturbance nor arousal predicted, or were predicted by variations in smoking. In short, smoking exhibits time-lagged, reciprocal relationships with craving and restlessness, and a one-way predictive relationship with negative affect. Temporal patterns of craving and restlessness may aid in the design of smoking cessation interventions.

Chang CW; Huang CW; Wu WH; Wang BE; Liu YL; Shen HC et al. Psychometric properties of the Chinese Craving Beliefs Questionnaire for heroin abusers in methadone treatment. BMC Psychiatry 11: article 39, 2011. (26 refs.)

Background: This paper reports the psychometric properties of the Chinese version of Craving Beliefs Questionnaire (CCBQ), an easy-to-administer assessment instrument of measurement of craving beliefs for heroin abusers. Methods: Participants were 445 heroin abusers from four methadone clinics in Northern Taiwan. Fifty-one of the participants were tested twice within a two-week period at a different hospital to examine test-retest reliability. Results: Three-factor solution using principal component analysis was identified in the CCBQ: will power, compulsive behavior, and negative coping, accounting for 54.6% of the variance. Internal consistency analysis indicated that the three factors have strong reliability, with Cronbach alphas ranging from .81 to .92. The test-retest ICC coefficient is .80. The test-retest coefficients for the subscales will power, compulsive behavior, and negative coping are .76, .51, and .64, respectively. Overall, the data show that the CCBQ has acceptable reliability and validity, demonstrating that it can be a research instrument for assessing heroin craving beliefs. Conclusions: The psychometric properties of the CCBQ seem promising for both research and clinical purposes, and the scale thus deserves further refinement and validation with heroin abusers.

Chase HW; Eickhoff SB; Laird AR; Hogarth L. The neural basis of drug stimulus processing and craving: An activation likelihood estimation meta-analysis. Biological Psychiatry 70(8): 785-793, 2011. (128 refs.)

Background: The capacity of drug cues to elicit drug-seeking behavior is believed to play a fundamental role in drug dependence; yet the neurofunctional basis of human drug cue-reactivity is not fully understood. We performed a meta-analysis to identify brain regions that are consistently activated by presentation of drug cues. Studies involving treatment-seeking and nontreatment-seeking substance users were contrasted to determine whether there were consistent differences in the neural response to drug cues between these populations. Finally, to assess the neural basis of craving, consistency across studies in brain regions that show correlated activation with craving was assessed. Methods: Appropriate studies, assessing the effect of drug-related cues or manipulations of drug craving in drug-user populations across the whole brain, were obtained via the PubMed database and literature search. Activation likelihood estimation, a method of quantitative meta-analysis that estimates convergence across experiments by modeling the spatial uncertainty of neuroimaging data, was used to identify consistent regions of activation. Results: Cue-related activation was observed in the ventral striatum (across both subgroups), amygdala (in the treatment-seeking subgroup and overall), and orbitofrontal cortex (in the nontreatment-seeking subgroup and overall) but not insula cortex. Although a different pattern of frontal and temporal lobe activation between the subgroups was observed, these differences were not significant. Finally, right amygdala and left middle frontal gyrus activity were positively associated with craving. Conclusions: These results substantiate the key neural substrates underlying reactivity to drug cues and drug craving.

Culbertson CS; Bramen J; Cohen MS; London ED; Olmstead RE; Gan JJ et al. Effect of bupropion treatment on brain activation induced by cigarette-related cues in smokers. Archives of General Psychiatry 68(5): 505- 515, 2011. (92 refs.)

Context: Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective: To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design:: Randomized, double-blind, before-after controlled trial. Setting: Academic brain imaging center. Participants: Thirty nicotine-dependent smokers (paid volunteers). Interventions: Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures: Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results: Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions: Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

Dawes GM; Sitharthan T; Conigrave KM; Phung N; Weltman M. Patients admitted for inpatient cannabis detoxification: Withdrawal symptoms and impacts of common comorbidities. Journal of Substance Use 16(5): 392-405, 2011. (31 refs.)

Introduction: There is clinical impetus to accurately monitor cannabis withdrawal symptoms. In doing this the impact of other drug and mental health comorbidities should be considered. Aims: To report patient demographics, psychiatric and substance use comorbidities and symptoms of cannabis withdrawal in the first 5 days of hospital admission for detoxification. Design: Daily self-reported symptom severity ratings were analysed as functions of gender, secondary drug use and recent mental health history. Setting: Specialised inpatient hospital unit for withdrawal management (detoxification) at a University of Sydney teaching hospital, Sydney, Australia. Participants: Total 193 consecutive patients admitted for routine inpatient cannabis withdrawal management over a 9-month period. Measurements: Patients screened via daily self-reported subjective ratings of cannabis withdrawal. Findings: Average cannabis used per day was 2.6 g. Most patients smoked tobacco daily (91%) and half of the sample (53%) reported other drug use. Alcohol was the main secondary drug used (29%). Half of the patients (51%) reported recent contact or interventions for mental health concerns. We were able to delineate principal withdrawal features to include "anxiety" (physical tension, hypermentation, palpitations and excessive worry), dysphoria (+ anergia, anhedonia, lethargy and somnolence) and irritability/agitation. Additional features identified included mood swings and cravings for cannabis. These features all significantly declined over a 5-day admission. Recent mental health concerns, but not gender or secondary drug use, correspond to greater global symptom severity over the course of admission. Conclusions: This study underscores a need to be alert to the impacts of comorbidities that are common in this treatment-seeking population, especially secondary drug use and the potential for mental health issues which add dimensions of complexity.

de los Cobos JP; Sinol N; Trujols J; Banuls E; Batlle F; Tejero A. Drug-dependent inpatients reporting continuous absence of spontaneous drug craving for the main substance throughout detoxification treatment. Drug and Alcohol Review 30(4): 403-410, 2011. (43 refs.)

Introduction and Aims. Drug craving is considered to be an essential component of substance dependence. We aimed to characterise drug-dependent inpatients reporting continuous absence of subjective spontaneous drug craving. Design and Methods. This is a 3 year chart-review study designed to compare drug-dependent inpatients who did not report craving everyday (non-cravers) and their counterparts who did (cravers). All participants were recruited consecutively and completed a 14 day detoxification treatment. Craving was defined as a desire to use the main detoxification substance. This substance was chosen by patients, who completed a craving visual analogue scale, the Beck Depression Inventory and the State-Trait Anxiety Inventory daily. The Temperament and Character Inventory and the Addiction Severity Index were also used. Results. Of the 195 patients who completed the detoxification treatment, 45 (23.1%) were non-cravers and 32 (16.4%) were cravers. The main detoxification substances were alcohol, benzodiazepines, cannabis, cocaine, heroin and methadone. Non-cravers named methadone as the main detoxification substance more frequently than cravers, and benzoylecgonine was less frequently present in their urine at treatment entry. A decreased score on the Temperament and Character Inventory dimension of harm avoidance (i.e. trait anxiety) was the only independent predictor of absence of craving (odds ratio = 1.16, 95% confidence interval = 1.03-1.31). During admission, non-cravers had lower Beck Depression Inventory and State-Trait Anxiety Inventory scores than cravers. These differences were not accounted for by pharmacological treatment. Discussion and Conclusions. Drug-dependent inpatients who report absence of craving are characterised by relatively low levels of depression and anxiety throughout detoxification treatment, and relatively low levels of trait anxiety.

Debruyne D; Courne MA; Le Boisselier R; Djezzar S; Gerardin M; Boucher A et al. Mephedrone: A designer drug of recent use in France. Therapie 65(6): 519-524, 2010. (16 refs.)

Designer drugs are currently marketed as substitutes for stimulant drugs as cocaine, amphetamine, MDMA. Unlike compounds listed as narcotics, these new substances are deliberately synthesized to avoid anti-drug laws. Among them, mephedrone (4-methylmethcatinone) that belongs to cathinone family, has been recently introduced in France. Users report positive euphoric and entactogenic effects. They also describe negative effects such as increased dependence towards the drug itself and larger craving for tobacco and alcohol. The numerous and various described adverse effects include psychoactive, digestive, cardiovascular... effects. Some fatality cases have been reported in scientific literature or in press and attributed to mephedrone often in association with other substances. Mephedrone has been listed as narcotic in several European countries and more recently in France.

D'Sa C; Fox HC; Hong AK; Dileone RJ; Sinha R. Increased serum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: A prospective study. Biological Psychiatry 70(8): 706-711, 2011. (36 refs.)

Background: Cocaine dependence is associated with high relapse rates, but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central brain-derived neurotrophic factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and whether it is predictive of subsequent relapse risk. Methods: Serum samples were collected across three consecutive mornings from 35 treatment-engaged, 3-week-abstinent cocaine-dependent inpatients (17 males/18 females) and 34 demographically matched hospitalized healthy control participants (17 males/17 females). Cocaine-dependent individuals were prospectively followed on days 14, 30, and 90 posttreatment discharge to assess cocaine relapse outcomes. Time to cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine use (quantity) were the main outcome measures. Results: High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared with healthy control participants (p < .001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: 1.09, p < .05), greater number of days (p < .05), and higher total amounts of cocaine used (p = .05). Conclusions: High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence.

Ehlers CL; Gizer IR; Gilder DA; Wilhelmsen KC. Linkage analyses of stimulant dependence, craving, and heavy use in American Indians. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics 156B(7): 772-780, 2011. (115 refs.)

Amphetamine-type substances are the second most widely used illicit drugs in the United States. There is evidence to suggest that stimulant use (cocaine and methamphetamine) has a heritable component, yet the areas of the genome underlying these use disorders are yet to be identified. This study's aims were to map loci linked to stimulant dependence, heavy use, and craving in an American Indian community at high risk for substance dependence. DSM diagnosis of stimulant dependence, as well as indices of stimulant "craving," and "heavy use," were obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 381 members of multiplex families using SOLAR. Stimulant dependence, stimulant "craving," and "heavy stimulant use," were all found to be heritable. Analyses of multipoint variance component LOD scores, failed to yield evidence of linkage for stimulant dependence. For the stimulant "craving" phenotype, linkage analysis revealed a locus that had a LOD score of 3.02 on chromosome 15q25.3-26.1 near the nicotinic receptor gene cluster. A LOD score of 2.05 was found at this same site for "heavy stimulant use." Additional loci with LOD scores above 2.00 were found for stimulant "craving" on chromosomes 12p13.33-13.32 and 18q22.3. These results corroborate the importance of "craving" as an important phenotype that is associated with regions on chromosome 12, 15, and 18, that have been highlighted in prior segregation studies in this and other populations for substance dependence-related phenotypes.

Ersche KD; Barnes A; Jones PS; Morein-Zamir S; Robbins TW; Bullmore ET. Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence. Brain 134(Part 7): 2013-2024, 2011. (96 refs.)

A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.

Fatseas M; Denis C; Massida Z; Verger M; Franques-Reneric P; Auriacombe M. Cue-induced reactivity, cortisol response and substance use outcome in treated heroin dependent individuals. Biological Psychiatry 70(8): 720-727, 2011. (46 refs.)

Background: Environmental stimuli associated with drug taking have been known to elicit drug craving and physiologic arousal, as well as hypothalamic-pituitary-adrenal axis activation. However, the relationship between these responses and substance use outcomes in heroin-dependent subjects has not been previously studied. We investigated the relationship among subjective and physiologic reactivity, biological stress response evoked in the laboratory, and relapse to substance use in treated opiate-dependent individuals. Methods: Eighteen opiate-abstinent methadone-or buprenorphine-treated patients and 13 control subjects were exposed to neutral-and drug-cue exposure laboratory sessions with a 3-month follow-up period. Exposure to cues involved both videotapes and handling during a 100-min session. Subjective craving, agonistic effects, withdrawal feelings, galvanic skin resistance, and salivary cortisol were assessed. Substance use outcome among patients was examined during the follow-up phase. Differences between relapsers, nonrelapsers, and controls were analyzed with respect to the data on drug-cue responsivity and on cortisol responses using repeated-measures analysis of variance. The association with substance use outcome was assessed using a nominal logistic model. Results: Relapsers experienced greater drug-cue induced subjective responses and an increased cortisol response compared with both nonrelapsers and control subjects. After adjusting on covariates, cue-induced cortisol response was associated with the relapser group and was highly correlated with self-reports of "high." Conclusions: Subjects defined as relapsers presented a higher cue-induced reactivity during the drug-cue exposure as well as an increased cortisol response to drug cues. Higher cortisol response to drug cues may increase relapse vulnerability in stable-dose buprenorphine or methadone-maintained subjects.

Fidler JA; West R. Enjoyment of smoking and urges to smoke as predictors of attempts and success of attempts to stop smoking: A longitudinal study. Drug and Alcohol Dependence 115(1-2): 30-34, 2011. (27 refs.)

Background: 'Enjoyment' and 'addiction' have been proposed as opposing reasons why people continue to smoke despite the manifest dangers. This study examined the roles of these as barriers to smoking cessation. Methods: 2257 smokers taking part in a national household survey completed postal-follow-up questionnaires 6 months later. Enjoyment of smoking was measured at baseline as was strength of urges to smoke during a normal smoking day as a subjective marker of addiction. Smoking status, quit attempts and quit success were assessed at follow-up. Data on age, sex, social grade and method of cessation support used were also collected. Associations between baseline measures and smoking outcomes were assessed using logistic regression. Results: Only enjoyment of smoking predicted whether a quit attempt was made (OR = 0.70, p < 0.001, 95% CI = 0.62-0.78) and only strength of urges to smoke predicted whether a quit attempt was successful (OR = 0.70, p < 0.001, 95% CI = 0.57-0.87). This pattern of results remained when controlling for sociodemographic factors and method of support used. Conclusions: Both enjoyment of smoking and strength of urges to smoke are important in the smoking cessation process, but in different ways. Interventions to promote cessation need to address both in order to maximise the rate of quit attempts and their chances of success.

Franklin T; Wang Z; Suh JJ; Hazan R; Cruz J; Li Y et al. Effects of varenicline on smoking cue-triggered neural and craving responses. Archives of General Psychiatry 68(5): 516- 526, 2011. (58 refs.)

Context: Varenicline, an effective smoking cessation medication, functions as an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist. It indirectly affects the dopaminergic reward system by reducing withdrawal symptoms during abstinence and by decreasing the reinforcement received from nicotine while smoking. We hypothesize that varenicline would have a third mechanism to blunt responses to smoking cues in the reward-related ventral striatum and medial orbitofrontal cortex and would be associated with a reduction in smoking cue-elicited craving. Design:: A laboratory model of conditioned responding and arterial spin-labeled perfusion functional magnetic resonance imaging, a biomarker of regional brain activity, was used to test our hypothesis. Perfusion functional magnetic resonance imaging is quantitative and stable across time, facilitating the measurement of medication-induced neural modifications in the brain in response to a challenge (smoking cue exposure) and in the brain in the resting condition (without provocation). Smokers were imaged during rest and during smoking cue exposure before and after a 3-week randomized placebo-controlled medication regimen. Subjects were nonabstinent to explicitly examine the effects of varenicline on cue reactivity independent of withdrawal. Setting: Center for the Study of Addictions, University of Pennsylvania, Philadelphia. Subjects: Subjects were nicotine-dependent smokers who responded to advertisements placed on local radio and Listservs to participate in a medication-related research study that specifically stated "this is not a Quit Smoking Study" and "smokers may be contemplating but not currently considering quitting." Results: Prerandomization smoking cues vs nonsmoking cues activated the ventral striatum and medial orbitofrontal cortex (t = 3.77) and elicited subjective reports of craving (P = .006). Craving reports correlated with increased activity in the posterior cingulate (t = 4.11). Administration of varenicline diminished smoking cue-elicited ventral striatum and medial orbitofrontal cortex responses (t values from -3.75 to -5.63) and reduced self-reported smoking cue-elicited craving, whereas placebo-treated subjects exhibited responses similar to those observed prior to randomization. Varenicline-induced activation of lateral orbitofrontal cortex in the brain at rest (t = 5.63) predicted blunting of smoking cue responses in the medial orbitofrontal cortex (r = -0.74). Conclusions: Varenicline's reciprocal actions in the reward-activated medial orbitofrontal cortex and in the reward-evaluating lateral orbitofrontal cortex underlie a diminished smoking cue response, revealing a distinctive new action that likely contributes to its clinical efficacy.

Franklin TR; Wang Z; Sciortino N; Harper D; Li Y; Hakun J et al. Modulation of resting brain cerebral blood flow by the GABA B agonist, baclofen: A longitudinal perfusion fMRI study. Drug and Alcohol Dependence 117(2-3): 176-183, 2011. (77 refs.)

Background: Preclinical studies confirm that the GABA B agonist, baclofen blocks dopamine release in the reward-responsive ventral striatum (VS) and medial prefrontal cortex, and consequently, blocks drug motivated behavior. Its mechanism in humans is unknown. Here, we used continuous arterial spin labeled (CASL) perfusion fMRI to examine baclofen's effects on blood flow in the human brain. Methods: Twenty-one subjects (all smokers, 12 females) were randomized to receive either baclofen (80 mg/day; N = 10) or placebo (N = 11). A five minute quantitative perfusion fMRI resting baseline (RB) scan was acquired at two time points; prior to the dosing regimen (Time 1) and on the last day of 21 days of drug administration (Time 2). SPM2 was employed to compare changes in RB from Time 1 to 2. Results: Baclofen diminished cerebral blood flow (CBF) in the VS and mOFC and increased it in the lateral OFC, a region involved in suppressing previously rewarded behavior. CBF in bilateral insula was also blunted by baclofen (T values ranged from -11.29 to 15.3 at p = 0.001, 20 contiguous voxels). CBF at Time 2 was unchanged in placebo subjects. There were no differences between groups in side effects or cigarettes smoked per day (at either time point). Conclusions: Baclofen's modulatory actions on regions involved in motivated behavior in humans are reflected in the resting state and provide insight into the underlying mechanism behind its potential to block drug-motivated behavior, in preclinical studies, and its putative effectiveness as an anti-craving/anti-relapse agent in humans.

Fricks-Gleason AN; Khalaj AJ; Marshall JF. Dopamine D1 receptor antagonism impairs extinction of cocaine-cue memories. Behavioural Brain Research 226(1): 357-360, 2012. (34 refs.)

Increasingly, research suggests a role for dopamine D1 receptors in the consolidation of extinction of both appetitive and aversive memories. However, a role for D1 receptors in extinction of memories involving drug reward has yet to be established. Here we show that post-retrieval, but not delayed, systemic administration of the D1 receptor antagonist SCH23390 results in prolonged extinction of cocaine conditioned place preference (CPP), suggesting a critical role for D1 receptors in the consolidation of extinction of cocaine-cue memories.

Fu M; Martinez-Sanchez JM; Agudo A; Pascual JA; Borras JM; Samet JM et al. Association between time to first cigarette after waking up and salivary cotinine concentration. Nicotine & Tobacco Research 13(3): 168-172, 2011. (24 refs.)

The time to first cigarette smoked after waking up appears to be a good predictor of plasma and urine cotinine levels; however, collection of blood and urine is difficult in population-based studies and may influence participation. We aimed to test whether time to first cigarette is associated with salivary cotinine. We used data from a cross-sectional study on a representative sample of the general population of Barcelona, Spain. We gathered information on smoking by means of a questionnaire and collected saliva for cotinine analysis. Of 1,245 participants, 22.9% were daily smokers, and the final sample for analysis consisted of 210 daily smokers. There were significant associations between salivary cotinine and time to first cigarette, between cigarette consumption and time to first cigarette, and between salivary cotinine and cigarette consumption. Salivary cotinine had decreased as time to first cigarette increased. After adjusting for cigarette consumption and sex, there were significant differences in mean salivary cotinine according to time to first cigarette (< 5 min: 219.2 ng/ml; 6-30 min: 175.8 ng/ml; 31-60 min: 168.5 ng/ml; > 60 min: 137.2 ng/ml). All paired comparisons were significant (p < .001) except in the 6- to 30-min group versus the 31- to 60-min group (p = .701). After adjustment for the number of cigarettes smoked in the last 24 hr, time to first cigarette is associated with salivary cotinine concentration.

Garcia-Rodriguez O; Ferrer-Garcia M; Pericot-Valverde I; Gutierrez-Maldonado J; Secades-Villa R; Carballo JL. Identifying specific cues andcontexts related to smoking: Craving for the development of effective virtual environments. Cyberpsychology, Behavior, and Social Networking 14(3): 91-97, 2011. (43 refs.)

Craving is considered the main variable associated with relapse after smoking cessation. Cue Exposure Therapy (CET) consists of controlled and repeated exposure to drug-related cues with the aim of extinguishing craving responses. Some virtual reality (VR) environments, such as virtual bars or parties, have previously shown their efficacy as tools for eliciting smoking craving. However, in order to adapt this technology to smoking cessation interventions, there is a need for more diverse environments that enhance the probability of generalization of extinction in real life. The main objective of this study was to identify frequent situations that produce smoking craving, as well as detecting specific craving cues in those contexts. Participants were 154 smokers who responded to an ad hoc self-administered inventory for assessing craving level in 12 different situations. Results showed that having a drink in a bar/pub at night, after having lunch/dinner in a restaurant and having a coffee in a cafe or after lunch/dinner at home were reported as the most craving-inducing scenarios. Some differences were found with regard to participants' gender, age, and number of cigarettes smoked per day. Females, younger people, and heavier smokers reported higher levels of craving in most situations. In general, the most widely cited specific cues across the contexts were people smoking, having a coffee, being with friends, and having finished eating. These results are discussed with a view to their consideration in the design of valid and reliable VR environments that could be used in the treatment of nicotine addicts who wish to give up smoking.

George O; Koob GF. Craving, context and the cortex. (editorial). Nature Neuroscience 14(4): 409-410, 2011. (15 refs.)

Hogarth L. The role of impulsivity in the aetiology of drug dependence: Reward sensitivity versus automaticity. Psychopharmacology 215(3): 567- 580, 2011. (138 refs.)

Impulsivity has long been known as a risk factor for drug dependence, but the mechanisms underpinning this association are unclear. Impulsivity may confer hypersensitivity to drug reinforcement which establishes higher rates of instrumental drug-seeking and drug-taking behaviour, or may confer a propensity for automatic (non-intentional) control over drug-seeking/taking and thus intransigence to clinical intervention. The current study sought to distinguish these two accounts by measuring Barratt Impulsivity and craving to smoke in 100 smokers prior to their completion of an instrumental concurrent choice task for tobacco (to measure the rate of drug-seeking) and an ad libitum smoking test (to measure the rate of drug-taking-number of puffs consumed). The results showed that impulsivity was not associated with higher rates of drug-seeking/taking, but individual differences in smoking uptake and craving were. Rather, nonplanning impulsivity moderated (decreased) the relationship between craving and drug-taking, but not drug-seeking. These data suggest that whereas the uptake of drug use is mediated by hypervaluation of the drug as an instrumental goal, the orthogonal trait nonplanning impulsivity confers a propensity for automatic control over well-practiced drug-taking behaviour.

Hughes JR. The hardening hypothesis: Is the ability to quit decreasing due to increasing nicotine dependence? A review and commentary. (review). Drug and Alcohol Dependence 117(2-3): 111-117, 2011. (55 refs.)

The "hardening hypothesis" states tobacco control activities have mostly influenced those smokers who found it easier to quit and, thus, remaining smokers are those who are less likely to stop smoking. This paper first describes a conceptual model for hardening. Then the paper describes important methodological distinctions (quit attempts vs. ability to remain abstinent as indicators, measures of hardening per se vs. measures of causes of hardening, and dependence measures that do vs. do not include cigarettes per day (cigs/day).) After this commentary, the paper reviews data from prior reviews and new searches for studies on one type of hardening: the decreasing ability to quit due to increasing nicotine dependence. Overall, all four studies of the general population of smokers found no evidence of decreased ability to quit; however, both secondary analyses of treatment-seeking smokers found quit rates were decreasing over time. Cigs/day and time-to-first cigarette measures of dependence did not increase over time; however, two studies found that DSM-defined dependence appeared to be increasing over time. Although these data suggest hardening may be occurring in treatment seekers but not in the general population of smokers, this conclusion may be premature given the small number of data sets and indirect measures of quit success and dependence in the data sets. Future studies should include questions about quit attempts, ability to abstain, treatment use, and multi-item dependence measures.

Jardin BF; LaRowe SD; Hall BJ; Malcolm RJ. The Obsessive Compulsive Cocaine Scale: Assessment of factor structure, reliability, and validity. Addictive Behaviors 36(12): 1223-1227, 2011. (29 refs.)

The present study assessed the factor structure, reliability, test retest, convergent validity, and predictive validity of the Obsessive Compulsive Cocaine Scale (OCCS), a newly developed questionnaire adapted from the Obsessive Compulsive Drinking Scale (OCDS). The questionnaire was administered to 189 cocaine-dependent individuals participating in two medication treatment trials for cocaine dependence. Confirmatory factor analysis of this measure revealed that it primarily assesses two factors, obsessions and compulsions. In addition, the data provided strong support for the internal consistency, test-retest reliability, predictive validity, and convergent validity of this two-factor measure. Overall, the data provide support for the psychometric strength of a modified version of the OCDS specifically designed to assess obsessive and compulsive cocaine use among those with cocaine dependence.

Javitz HS; Swan GE; Lerman C. The dynamics of the urge-to-smoke following smoking cessation via pharmacotherapy. Addiction 106(10): 1835-1845, 2011. (25 refs.)

Aims: To examine person-specific urge-to-smoke trajectories during the first 7 days of abstinence and the relationship of trajectory parameters to continuous abstinence, demographics, medication and smoking history. Design: Hierarchical linear modeling was used to model person-specific trajectories for urge-to-smoke. Setting: Two university-based smoking cessation trials. Participants: Treatment-seeking smokers in a clinical trial of transdermal nicotine (n = 275) versus nicotine spray (n = 239) and of bupropion (n = 223) versus placebo (n = 198). Measurements: Self-reported urge-to-smoke for 7 days after the planned quit date, and 7-day point prevalence and continuous abstinence at end of treatment (EOT) and 6 months. Findings: Urge-to-smoke trajectory parameters (average level, slope, curvature and volatility) varied substantially among individuals, had modest intercorrelations and predicted continuous and point prevalence abstinence at EOT and at 6 months. Higher trajectory level, slope and volatility were all significantly (P <= 0.001) associated with a reduced likelihood of abstinence at EOT (odds ratios 0.44-0.75) and at 6-month follow-up (odds ratios from 0.63 to 0.78), controlling for demographic, medication and smoking use variables. Conclusion: Higher urge-to-smoke trajectory parameters of level, slope and volatility (measured over 7 days) predict continuous and 7-day point prevalence at EOT and 6 months. Although there were some associations of trajectory parameters with demographics and smoking history, the associations of trajectory parameters with relapse were relatively uninfluenced by demographics and smoking history.

Jenks RA; Higgs S. Reactivity to smoking- and food-related cues in currently dieting and non-dieting young women smokers. Journal of Psychopharmacology 25(4): 520-529, 2011. (58 refs.)

There is some evidence to suggest that young women dieters who smoke experience greater cigarette cravings in the presence of food-related related cues. The aim of this experiment was to examine reactivity to both smoking-related and water cues by dieting and non-dieting women smokers in the presence or absence of food cues. Eighteen female undergraduates attended two sessions (food present and food absent). At each session, participants were presented with a cigarette and water cue in a counterbalanced order. Pre- and post-cue measures included the brief version of the Questionnaire for Smoking Urges, heart rate and self-reported mood. All smokers showed enhanced reactivity (increased craving and heart rate) to smoking versus water cues. For dieters there was a larger increase in cigarette craving and heart rate in response to the smoking-related cues in the presence of food compared with the absence of food, whereas for non-dieters there was a smaller increase in cigarette craving and heart rate in response to the smoking-related cues in the presence of food compared with the absence of food. Mood and appetite ratings were not significantly affected by either cue type or session. The results suggest that cue reactivity to smoking-related cues is modulated by the presence of incentive stimuli relevant to the individual.

Jobes ML; Ghitza UE; Epstein DH; Phillips KA; Heishman SJ; Preston KL. Clonidine blocks stress-induced craving in cocaine users. Psychopharmacology 218(1, special issue): 83-88, 2011. (35 refs.)

Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. Healthy, non-treatment-seeking cocaine users (n = 59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose x Script interactions were not significant. Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

Karam-Hage M; Strobbe S; Robinson JD; Brower KJ. Bupropion-SR for smoking cessation in early recovery from alcohol dependence: A placebo-controlled, double-blind pilot study. American Journal of Drug and Alcohol Abuse 37(6): 487-490, 2011. (18 refs.)

We conducted a double-blind pilot study involving 11 alcohol-and nicotine-dependent patients randomized to receive either bupropion or placebo. Four of six patients on bupropion and one of five patients on placebo were abstinent from smoking at the end of medication phase. Those in the bupropion group reported significantly less craving (p < .02) and less exposure to cigarette smoke over time (expired carbon monoxide; p < .01). There were no serious adverse events and no main effects of medication group on either per subject or total number of adverse events. All those who completed treatment remained abstinent from alcohol.

Kovac VB; Rise J. The role of desire in the prediction of intention: The case of smoking behavior. Swiss Journal of Psychology 70(3): 141-148, 2011. (34 refs.)

This paper is based on the notion that desire represents an important motivational aspect of the decision-making process. Thus, we examined the hypotheses that desire (1) predicts behavioral intentions and (2) mediates the effects of theory of planned behavior (TPB) components and past behavior on an individual's intention to quit smoking. The analysis is based on three separate conditions in which the intention to quit smoking during the next 1, 4, or 6 months, respectively, was measured; the three conditions contained identical variables. The results of the hierarchical regression analysis show that there are sufficient grounds for including desire as an additional predictor in the TPB model. The results also show that desire mediates the effects of attitudes, norms, and past behavior on intention. However, the mediating role of desire was not obtained for the relationship between PBC and intention. Theoretical implications and recommendations for future research are suggested.

Lee DC; Perkins KA; Zimmerman E; Robbins G; Kelly TH. Effects of 24 hours of tobacco withdrawal and subsequent tobacco smoking among low and high sensation seekers. Nicotine & Tobacco Research 13(10): 943-954, 2011. (49 refs.)

Introduction: Previous studies have indicated that high sensation seekers are more sensitive to the reinforcing effects of nicotine, initiate smoking at an earlier age, and smoke greater amounts of cigarettes. This study examined the influence of sensation-seeking status on tobacco smoking following deprivation in regular tobacco users. Methods: Twenty healthy tobacco-smoking volunteers with low or high impulsive sensation-seeking subscale scores completed 2 consecutive test days per week for 3 consecutive weeks. Each week, a range of self-report, performance, and cardiovascular assessments were completed during ad libitum smoking on Day 1 and before and after the paced smoking of a tobacco cigarette containing 0.05, 0.6, or 0.9 mg of nicotine following 24 hr of tobacco deprivation on Day 2. In addition, self-administration behavior was analyzed during a 2-hr free access period after the initial tobacco administration. Results: In high sensation seekers, tobacco smoking independent of nicotine yield ameliorated deprivation effects, whereas amelioration of deprivation effects was dependent on nicotine yield among low sensation seekers. However, this effect was limited to a small subset of measures. Subsequent cigarette self-administration increased in a nicotine-dependent manner for high sensation seekers only. Conclusions: Compared with low sensation seekers, high sensation seekers were more sensitive to the withdrawal relieving effects of non-nicotine components of smoking following 24 hr of deprivation on selective measures and more sensitive to nicotine yield during subsequent tobacco self-administration. These results are consistent with studies suggesting that factors driving tobacco dependence may vary as a function of sensation-seeking status.

Littel M; Franken IHA. Implicit and explicit selective attention to smoking cues in smokers indexed by brain potentials. Journal of Psychopharmacology 25(4): 503-513, 2011. (50 refs.)

Substance use disorders are characterized by cognitive processing biases, such as automatically detecting and orienting attention towards drug-related stimuli. However, it is unclear how, when and what kind of attention (i.e. implicit, explicit) interacts with the processing of these stimuli. In addition, it is unclear whether smokers are hypersensitive to emotionally significant cues in general or to smoking-related cues in particular. The present event-related potential study aimed to enhance insight in drug-related processing biases by manipulating attention for smoking and other motivationally relevant (emotional) cues in smokers and non-smokers using a visual oddball task. Each of the stimulus categories served as a target (explicit attention; counting) or as a non-target (implicit attention; oddball) category. Compared with non-smokers, smokers' P300 (350-600 ms) was enhanced to smoking pictures under both attentional conditions. P300 amplitude did not differ between groups in response to positive, negative, and neutral cues. It can be concluded from this study that attention manipulation affects the P300 differently in smokers and non-smokers. Smokers display a specific bias to smoking-related cues, and this bias is present during both explicit and implicit attentional processing. Overall, it can be concluded that both explicit and implicit attentional processes appear to play an important role in drug-related processing bias.

Liu JX; Qin W; Yuan K; Li J; Wang W; Li Q et al. Interaction between dysfunctional connectivity at rest and heroin cues-induced brain responses in male abstinent heroin-dependent Individuals. PLoS ONE 6(10): e23098, 2011. (51 refs.)

Background: The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). Methodology/Principal Findings: We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. Conclusions: These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence.

Lochbuehler K; Voogd H; Scholte RHJ; Engels RCME. Attentional bias in smokers: Exposure to dynamic smoking cues in contemporary movies. Journal of Psychopharmacology 25(4): 514-519, 2011. (28 refs.)

Research has shown that smokers have an attentional bias for pictorial smoking cues. The objective of the present study was to examine whether smokers also have an attentional bias for dynamic smoking cues in contemporary movies and therefore fixate more quickly, more often and for longer periods of time on dynamic smoking cues than non-smokers. By drawing upon established methods for assessing attentional biases for pictorial cues, we aimed to develop a new method for assessing attentional biases for dynamic smoking cues. We examined smokers' and non-smokers' eye movements while watching a movie clip by using eye-tracking technology. The sample consisted of 16 smoking and 17 non-smoking university students. Our results confirm the results of traditional pictorial attentional bias research. Smokers initially directed their gaze more quickly towards smoking-related cues (p = 0.01), focusing on them more often (p = 0.05) and for a longer duration (p = 0.01) compared with non-smokers. Thus, smoking cues in movies directly affect the attention of smokers. These findings indicate that the effects of dynamic smoking cues, in addition to other environmental smoking cues, need to be taken into account in smoking cessation therapies in order to increase successful smoking cessation and to prevent relapses.

Long CG; Hall L; Dolley O; Hollin CR. Substance-abusing women in a medium secure psychiatric setting: characteristics and psychometric test performance. Journal of Substance Use 16(3): 230- 242, 2011. (64 refs.)

Aims: The aim is to describe the characteristics and psychometric test performance of women admitted to a medium secure hospital. Method: Consecutive admission was classified into risk-relevant categories using case note data. Responses to psychometric measures of dependence, substance-related problems, self-efficacy, motivation for change, craving and coping were assessed. Results: Forty-four out of 55 consecutive admissions had a risk-relevant pattern of substance use before admission. Analysis of psychometric test performance produced two groups of patients differentiated according to self-efficacy, craving and belief in the benefits of change. Conclusions: Although further work needs to be done in assessing the applicability of specific psychometrics to specialist populations, findings reinforce the importance of matching treatment interventions to stages of readiness to change.

Lunell E; Curvall M. Nicotine delivery and subjective effects of Swedish portion snus compared with 4 mg nicotine polacrilex chewing gum. Nicotine & Tobacco Research 13(7): 573-578, 2011. (28 refs.)

Snus availability has been claimed to have contributed to the low rates of smoking among Swedish men and made possible the transfer to a less harmful form of nicotine dependence. Fourteen cigarette smokers were randomly assigned to 2 types of 1 g Swedish portion snus and 4 mg nicotine polacrilex (NP) chewing gum in open-label, single-dose crossover study. Nicotine delivery and pharmacokinetics were estimated, and self-reports of subjective effects were obtained using Visual Analogue Scales (VASs). Extracted dose from the NP gum averaged 2.56 mg compared with 2.12 and 2.18 mg, respectively, for Swedish portion snus. This resulted in a slightly larger area under the curve (AUC) for the NP chewing gum. The rise of the nicotine plasma concentration was faster for Swedish snus. Median T(max) was shorter, 30 min for snus compared with 45 min for the NP gum. The lower C(max) of NP gum compared with the snus products in spite of larger AUC may be explained by slower absorption from the chewing gum. The faster absorption of nicotine from Swedish portion snus was mirrored in a higher VAS score for "head rush." Craving/urges to smoke decreased similarly for all treatments. Salivation and throat burn were rated higher for the 4 mg NP gum compared with both types of snus. Swedish snus produced higher maximum blood nicotine concentration in shorter time and with a quicker onset of "head rush" compared with 4 mg NP chewing gum in spite of a smaller extracted dose. The quicker onset of "head rush" and supposedly higher satisfaction from snus may partly explain the widespread use of snus for stopping smoking in Sweden.

McClernon FJ; Van Voorhees EE; English J; Hallyburton M; Holdaway A; Kollins SH. Smoking withdrawal symptoms are more severe among smokers with ADHD and independent of ADHD symptom change: Results from a 12-day contingency-managed abstinence trial. Nicotine & Tobacco Research 13(9): 784-792, 2011. (36 refs.)

Introduction: Smokers with attention deficit hyperactivity disorder (ADHD) have greater difficulty quitting than those without ADHD, but preliminary data (McClernon, Kollins, Lutz, Fitzgerald, Murray, Redman, et al., 2008) suggest equivalent severity of withdrawal symptoms following brief abstinence. The objective of this study was to characterize the differential effects of intermediate term smoking abstinence on self-reported withdrawal and ADHD symptoms in adult smokers with and without ADHD. Methods: Forty adult (50% female), nontreatment seeking moderate-to-heavy smokers with and without ADHD were enrolled in a 12-day quit study in which monetary incentives were provided for maintaining biologically verified abstinence. Self-reported withdrawal, mood, and ADHD symptoms were measured pre- and post-quitting. Results: ADHD and controls did not vary on smoking or demographic variables. Significant Group x Session interactions were observed across a broad range of withdrawal symptoms and were generally characterized by greater withdrawal severity among ADHD smokers, particularly during the first 5 days of abstinence. In addition, Group x Sex x Session interactions were observed for craving, somatic symptoms, negative affect, and habit withdrawal; these interactions were driven by greater withdrawal severity among females with ADHD. Group x Session interactions were not observed for ADHD symptom scales. Conclusions: The results of this study suggest that smokers with ADHD, and ADHD females in particular, experience greater withdrawal severity during early abstinence-independent of effects on ADHD symptoms. Whereas additional research is needed to pinpoint mechanisms, our findings suggest that smoking cessation interventions targeted at smokers with ADHD should address their more severe withdrawal symptoms following quitting.

McKee SA; Sinha R; Weinberger AH; Sofuoglu M; Harrison ELR; Lavery M et al. Stress decreases the ability to resist smoking and potentiates smoking intensity and reward. Journal of Psychopharmacology 25(4): 490-502, 2011. (83 refs.)

We have developed a novel human laboratory model to examine two primary aspects of stress-precipitated tobacco relapse: (1) Does stress reduce the ability to resist the first cigarette? (2) Once the first cigarette is initiated, does stress facilitate subsequent smoking? Using a within-subject design, daily smokers (n = 37) who were nicotine deprived overnight received a personalized imagery induction (stress or neutral) on two separate days, and then had the option of initiating a tobacco self-administration session or delaying initiation for up to 50 min in exchange for three levels of monetary reinforcement. Subsequently, the tobacco self-administration session entailed a 1-hour period in which subjects could choose to smoke using a smoking topography system. Following the stress induction, subjects were less able to resist smoking, smoked more intensely (increased puffs, shorter inter-puff interval, and greater peak puff velocity), and perceived greater satisfaction and reward from smoking. Stress significantly increased hypothalamus-pituitary-adrenal (HPA) axis reactivity, tobacco craving, negative emotion, and physiologic reactivity relative to the neutral condition. In addition, increased cortisol, ACTH, and tobacco craving were associated with reduced ability to resist smoking following stress. These findings have implications for understanding the impact of stress on smoking relapse and model development to assess smoking lapse behavior.

McRae-Clark AL; Carter RE; Price KL; Baker NL; Thomas S; Saladin ME et al. Stress- and cue-elicited craving and reactivity in marijuana-dependent individuals. Psychopharmacology 218(1, special issue): 49-58, 2011. (52 refs.)

Cue-elicited craving and stress responses have been identified as predictors of relapse in drug dependence, but little research exists on the contribution of these factors to marijuana use specifically. The aims of the present study were to evaluate (1) responses to a psychological stressor, (2) responses to marijuana-related cues, and (3) if an exposure to a psychological stressor augmented craving subsequently elicited by marijuana-related cue exposure in marijuana-dependent individuals. Subjective (craving, stress), neuroendocrine (adrenocorticotropic hormone (ACTH), cortisol), and physiologic responses to the presentation of neutral and marijuana cues were assessed after randomization to a stress (Trier Social Stress Task (TSST)) or non-stress control condition in marijuana-dependent individuals. Outcome measures were assessed at baseline, post-stressor/pre-neutral cue, post-neutral cue, and post-marijuana cue. Eighty-seven participants completed procedures (stress group, n = 45; non-stress group, n = 42). The stress group had a significant increase over the non-stress group in stress rating (p < 0.001), craving (p = 0.028), cortisol (p < 0.001), and ACTH (p < 0.001) after the completion of the TSST. An increased craving response for all participants was seen following the presentation of the marijuana cues (p = 0.005). Following the TSST or non-stress condition, the non-stress group had an increase in craving to marijuana cues as compared to neutral cues (p = 0.002); an increase in craving was not observed in the stress group (p = 0.404). Marijuana cue exposure and a social stressor increased craving in marijuana-dependent individuals. Completion of the TSST did not increase craving response to subsequent marijuana cue exposure.

Meini M; Moncini M; Cecconi D; Cellesi V; Biasci L; Simoni G et al. Aripiprazole and ropinirole treatment for cocaine dependence: Evidence from a pilot study. (review). Current Pharmaceutical Design 17(14): 1376-1383, 2011. (49 refs.)

Background: Currently, there is no specific pharmacological therapy with established efficacy for the treatment of cocaine dependence. The aim of this study was to determine the safety, tolerability and the effects of aripiprazole and ropinirole in patients with cocaine dependence. Methods: This randomized clinical trial of 12-week duration was carried out on 28 consecutive patients with cocaine dependence presenting for treatment. The diagnostic assessment was performed using ICD-9-CM criteria and Mini International Neuropsychiatric Interview. The Clinical Global Impression Scale, a Visual Analogue Scale to assess craving and a self-report questionnaire on the use of cocaine were administered at baseline and then weekly throughout the study. Urinalyses were carried out three times per weeks to search for benzoylecgonine. Results: Of the 28 study participants, 14 completed the protocol. Treatment discontinuation was unrelated with side effects. One patient required a dosage reduction of ropinirole because of sleepiness and one patient assigned to aripiprazole who reported moderate akathysia had the dosage reduced to 5 mg/day. Routine blood works did not show significant changes from baseline and the overall proportion of positive urinalyses for benzoylecgnonine did not differ significantly between treatments. Using linear mixed-effect models a significant decrease in craving was found in the overall sample (p<0.001). The mean number of cocaine administrations exhibited a faster decrease with aripiprazole compared with ropinirole (p=0.009). Conclusions: Our pilot study indicates that cocaine craving decreases with both aripiprazole and ropinirole treatment but aripiprazole is more efficacious in reducing cocaine use.

Mickens L; Greenberg J; Ameringer KJ; Brightman M; Sun P; Leventhal AM. Associations between depressive symptom dimensions and smoking dependence motives. Evaluation & the Health Professions 34(1): 81-102, 2011. (41 refs.)

Depressive symptoms are heterogeneous and can be parsed into four subdimensions (i.e., positive affect [PA], negative affect [NA], somatic features [SF], and interpersonal problems [IP]) that may have unique associations with the motivation to smoke. This study explored associations between depressive symptom dimensions and 13 theoretically distinct domains of smoking dependence motivation in current cigarette smokers (N = 212; 53% female, mean [M] age = 24 years). Results demonstrated substantial variability in the pattern of motivational correlates across depressive dimensions. Low PA exhibited the narrowest motivational profile, associating with only the tendency to prioritize smoking over other reinforcers. NA demonstrated a broader profile, associating with smoking for affect regulation and cognitive enhancement as well as prioritizing smoking. SF associated with prioritizing smoking and smoking because of cue exposure, craving, and weight control. IP demonstrated the broadest profile, associating with 7 of 13 motivational domains. These findings may assist the tailoring cessation interventions for smokers with depressive symptoms.

Mihindou C; Vouillac C; Koob GF; Ahmed SH. Preclinical validation of a novel cocaine exposure therapy for relapse prevention. Biological Psychiatry 70(6): 593-598, 2011. (46 refs.)

Background: Cocaine not only induces intense rewarding sensations but also craving for more cocaine, particularly during abstinence, an effect that contributes, together with other factors, to relapse. Here we sought to prevent this effect by extinguishing the conditioned interoceptive cues of cocaine that are thought to be acquired during repeated cocaine use. Methods: Cocaine-induced craving was studied in rats using the well-validated model of drug-primed reinstatement of cocaine seeking. To extinguish the conditioned interoceptive effects of cocaine, rats received daily repeated cocaine priming in the absence of drug reinforcement. Results: Cocaine-primed reinstatement of cocaine seeking dramatically decreased with repeated cocaine priming regardless of the testing dose and even following a history of extended access to cocaine self-administration. The extinction of cocaine-primed reinstatement of cocaine seeking was enduring, generalized to stress-another major trigger of drug craving and relapse-and was context-dependent. Conclusions: These findings clearly show that it is feasible to prevent the ability of cocaine and stress to induce cocaine seeking using an approach designed to extinguish the drug's conditioned interoceptive cues. Although this preclinical extinction approach has limitations that need to be overcome in future research (i.e., its context-dependency), it may nevertheless represent a promising basis for the development of a novel exposure therapy against cocaine relapse.

Moon J; Lee JH. Predicting cigarette-seeking behavior: How reward sensitivity and positive emotions influence nicotine cravings. Social Behavior and Personality 39(6): 737-746, 2011. (16 refs.)

Reward sensitivity is a primary indicator of impulsive behavior, such as cigarette smoking, and contributes to positive emotional experiences. The aim in this study was to examine smokers' emotional experiences and cravings in relation to their personality traits. Participants were divided into high- and low-reward sensitivity groups, and a procedure aimed at inducing emotions was conducted while physiological responses were recorded. There was a significant difference in the subjective experiences of the 2 groups, and a significant positive correlation existed between a positive emotional experience and craving cigarettes. Furthermore, reward sensitivity induced craving in smokers and the relationship was mediated by positive emotion. We believe that the identified mediating effect of positive emotions on craving could provide a better understanding of maladaptive behavior associated with positive emotion and may play an important role in treatment of nicotine dependence.

Myers MG; Gwaltney CJ; Strong DR; Ramsey SE; Brown RA; Monti PM et al. Adolescent first lapse following smoking cessation: Situation characteristics, precipitants and proximal influences. Addictive Behaviors 36(12): 1253-1260, 2011. (46 refs.)

Despite increased attention to adolescent smoking cessation, little is known about adolescent relapse following a quit attempt. To address this issue, the present study was designed to provide initial information regarding the characteristics of adolescent lapses to smoking following abstinence. Included in the present study were 204 adolescent participants in four independent smoking cessation trials. For the full sample, participants averaged 15.99 (1.27) years of age; 56% were female and 78% were white. Lapse characteristics and precipitants were assessed using the Adolescent Smoking Relapse Review. Three domains of the lapse experience were assessed: lapse situation characteristics. precipitants of use in the situation, and proximal influences (i.e., potential precipitants occurring on the same day, prior to the lapse situation). Participant reports indicated that the modal lapse situation occurred in the evening while socializing with friends at home. Urges or cravings and social pressure were commonly endorsed as occurring in lapse situations. The most frequently reported proximal influence was desire for a cigarette, followed by abstinence-violation cognitions (okay to smoke occasionally, wanted to see what it would be like) and negative emotions. The findings indicate that a broad range of factors appear to influence adolescent smoking lapse and commend the value of incorporating content relevant to managing social and affective cues, strategies for inhibiting the prepotent response to ask for a cigarette, addressing cognitions regarding the difficulty of not smoking (i.e., cessation expectancies) and combating perceptions of the ability to smoke occasionally.

Nappo SA; Sanchez Z; De Oliveira LG. Crack, AIDS, and women in Sao Paulo, Brazil. Substance Use & Misuse 46(4): 476-485, 2011. (43 refs.)

Brazil is currently experiencing a growing number of newly recorded cases of HIV infection among women, with transmission mainly occurring by sex. This increase may be associated with the development of sexually risky behavior among female crack users who, according to informal reports, prostitute themselves for drugs or for money to be used for buying drugs. Since epidemiologic studies have not yet addressed this phenomenon, the aim of this study was to investigate this in depth using a qualitative ethnographic approach. An intentional sample was utilized, composed of 75 female crack users in Sao Paulo, who were selected by specific criteria using the snowball strategy and key informants. Fourteen different chains of users were investigated, allowing us to include the largest possible number and variety of users. Each participant was submitted to a semi-structured in-depth interview that was guided by a questionnaire. Verbal information was corroborated and extended using participative observation. These 14-45-year-old women, who had little schooling and no job connections, opted to sell their bodies as a strategy to obtain drugs and to satisfy their compulsive use of crack. The subjects engaged in up to nine acts of sexual intercourse per day, in unsafe locations and with multiple partners who were approached in a besieging way and selected using subjective criteria. These crack users generally exchanged sex under craving for ridiculously low prices and left the use of protection up to the client. Because the users used inadequate pipes to smoke crack, it was common for them to have lesions on their lips and mouths. Since they often provided oral sex, they exposed themselves to considerable risk for infection with STDs including HIV, because of the contact of their partners" semen with their open wounds. These women make up an important risk group with respect to the transmission of STDs including AIDS.

Nickerson LD; Ravichandran C; Lundahl LH; Rodolico J; Dunlap S; Trksak GH et al. Cue reactivity in cannabis-dependent adolescents. Psychology of Addictive Behaviors 25(1): 168-173, 2011. (33 refs.)

The authors measured event-related potentials with a craving manipulation to investigate the neural correlates of drug cue reactivity in 13 adolescents who are cannabis dependent (CD; ages 14-17). The P300 responses to marijuana (MJ) pictures (MJ-P300) and control pictures (C-P300) were assessed after handling neutral objects and again after handling MJ paraphernalia (MJP). Self-reported drug craving and heart rates also were measured. MJ-P300 were larger than C-P300 (p < .001), and both the MJ-P300 and craving increased significantly after handling MJP (p = .002 and p = .003, respectively), with no association between the magnitude of craving and MJ-P300. Heart rates were not affected by handling MJP. The results showed that adolescents who are CD have an attentional bias to MJ stimuli that increases after handling marijuana paraphernalia. Generally, the results are consistent with what has been reported for adult heavy chronic cannabis smokers, although there were some differences that require further investigation.

Paris MM; Carter BL; Traylor AC; Bordnick PS; Day SX; Armsworth MW et al. Cue reactivity in virtual reality: The role of context. Addictive Behaviors 36(7): 696-699, 2011. (14 refs.)

Cigarette smokers in laboratory experiments readily respond to smoking stimuli with increased craving. An alternative to traditional cue-reactivity methods (e.g., exposure to cigarette photos), virtual reality (VR) has been shown to be a viable cue presentation method to elicit and assess cigarette craving within complex virtual environments. However, it remains poorly understood whether contextual cues from the environment contribute to craving increases in addition to specific cues, like cigarettes. This study examined the role of contextual cues in a VR environment to evoke craving. Smokers were exposed to a virtual convenience store devoid of any specific cigarette cues followed by exposure to the same convenience store with specific cigarette cues added. Smokers reported increased craving following exposure to the virtual convenience store without specific cues, and significantly greater craving following the convenience store with cigarette cues added. However, increased craving recorded after the second convenience store may have been due to the pre-exposure to the first convenience store. This study offers evidence that an environmental context where cigarette cues are normally present (but are not), elicits significant craving in the absence of specific cigarette cues. This finding suggests that VR may have stronger ecological validity over traditional cue reactivity exposure methods by exposing smokers to the full range of cigarette-related environmental stimuli, in addition to specific cigarette cues, that smokers typically experience in their daily lives.

Piasecki TM; Jahng S; Wood PK; Robertson BM; Epler AJ; Cronk NJ et al. The subjective effects of alcohol-tobacco co-use: An ecological momentary assessment investigation. Journal of Abnormal Psychology 120(3): 557-571, 2011. (67 refs.)

Alcohol and tobacco use covary at multiple levels of analysis, and co-use of the 2 substances may have profound health consequences. To characterize the motivationally relevant processes contributing to co-use, the current study used ecological momentary assessment (EMA) to examine the subjective consequences of naturally occurring simultaneous use of alcohol and tobacco. Current smokers who reported frequently drinking alcohol (N = 259) used electronic diaries to monitor their daily experiences for 21 days. Participants responded to prompted assessments and also initiated recordings when they smoked a cigarette or completed the first drink in a drinking episode. Momentary reports of smoking and alcohol consumption were associated with one another, and these effects remained after adjustment for occasion- and person-level covariates. When participants consumed alcohol, they reported increased pleasure and decreased punishment from the last cigarette. Smoking was associated with small increases in pleasure from the last drink. Ratings of buzzed and dizzy were synergistically affected by co-use of alcohol and tobacco. Co-use was also followed by higher levels of craving for both alcohol and tobacco. Results point to the importance of reward and incentive processes in ongoing drug use and suggest that alcohol intensifies real-time reports of the motivational consequences of smoking more strongly than smoking affects corresponding appraisals of alcohol effects.

Pickens CL; Airavaara M; Theberge F; Fanous S; Hope BT; Shaham Y. Neurobiology of the incubation of drug craving. (review). Trends in Neurosciences 34(8): 411-420, 2011. (118 refs.)

It was suggested in 1986 that cue-induced drug craving in cocaine addicts progressively increases over the first several weeks of abstinence and remains high for extended periods. During the past decade, investigators have identified an analogous incubation phenomenon in rodents, in which time-dependent increases in cue-induced drug seeking are observed after withdrawal from intravenous cocaine self-administration. Such an incubation of drug craving is not specific to cocaine, as similar findings have been observed after self-administration of heroin, nicotine, methamphetamine and alcohol in rats. In this review, we discuss recent results that have identified important brain regions involved in the incubation of drug craving, as well as evidence for the underlying cellular mechanisms. Understanding the neurobiology of the incubation of drug craving in rodents is likely to have significant implications for furthering understanding of brain mechanisms and circuits that underlie craving and relapse in human addicts.

Preston KL; Epstein DH. Stress in the daily lives of cocaine and heroin users: Relationship to mood, craving, relapse triggers, and cocaine use. Psychopharmacology 218(1, special issue): 29-37, 2011. (33 refs.)

Quantitative real-time data on the stress experienced by drug misusers in their daily lives may provide additional insight into stress's role in drug use. The purpose of this study is to evaluate stress in relation to craving, mood, relapse-trigger exposure, and cocaine use in cocaine-dependent outpatients. Methadone-maintained cocaine- and heroin-abusing outpatients (N = 114) provided ecological momentary assessment data on handheld computers. Ratings of stress were compared to those of craving and mood and past-hour exposure to putative drug-use triggers in randomly prompted entries and in the 5 h prior to participant-initiated cocaine use reports. Stress had significant positive relationships with current ratings of craving for cocaine, heroin, and tobacco and with ratings of tiredness, boredom, and irritation, and had significant negative relationships with ratings of happiness and relaxation. Stress was significantly greater in entries in which participants also reported past-hour exposure to negative-mood triggers, most of the drug-exposure triggers, or any trigger involving thoughts about drugs (e.g., tempted out of the blue). The linear increase in stress during the 5-h preceding individual episodes of cocaine use was not significant (p = 0.12), though there was a trend for such an increase before the use episodes that participants attributed to stressful states when they occurred (p = 0.87). The findings suggest a complex role of stress in addiction. Stress reported in real time in the natural environment showed strong cross-sectional momentary relationships with craving, mood, and exposure to drug-use trigger. However, the prospective association between stress ratings and cocaine-use episodes was, at best, weak.

Reichel CM; See RE. Chronic N-acetylcysteine after cocaine self-administration produces enduring reductions in drug-seeking. (editorial). Neuropsychopharmacology 37(1): 298-298, 2012. (6 refs.)

Rogojanski J; Vettese LC; Antony MM. Role of sensitivity to anxiety symptoms in responsiveness to mindfulness versus suppression strategies for coping with smoking cravings. Journal of Clinical Psychology 67(4): 439-445, 2011. (31 refs.)

Mindfulness strategies for managing cravings involve present-moment, nonjudgmental awareness of cravings without acting on them, while suppression involves pushing cravings out of awareness. Few studies have investigated individual differences in responding to these strategies. The current study examined whether individual differences in anxiety sensitivity moderate responsiveness to mindfulness versus suppression for coping with smoking cravings. Participants (N = 61) utilized a mindfulness or suppression strategy to manage cravings during cue exposure to cigarettes and were evaluated for self-efficacy 7 days later. Greater anxiety sensitivity after cue exposure was associated with increased self-efficacy in the suppression condition. This suggests that anxiety-sensitive individuals who utilize suppression may cope better with cravings, at least in the early days after learning these strategies.

Roozen HG; van der Kroft P; van Marle HJ; Franken IHA. The impact of craving and impulsivity on aggression in detoxified cocaine-dependent patients. Journal of Substance Abuse Treatment 40(4): 414- 418, 2011. (38 refs.)

Patients with substance use disorders are frequently associated with impulsivity that may underlie elevated levels life-threatening types of behavior, including aggression. In addition, craving is a prominent feature of addiction and appears to be closely related to impulsivity. This study assessed the unique contribution of cocaine craving and impulsivity in predicting aggression by means of correlational and mediational analyses. Forty inpatient detoxified cocaine-dependent patients and 40 matched healthy controls were enrolled. These participants filled out the Obsessive Compulsive Drug Use Scale, the Dickman Impulsivity Inventory, and the Aggression Questionnaire. The patient group showed elevated levels of impulsivity and aggression as compared with the control group. Although cocaine craving is positively correlated with both impulsivity and aggression, craving did not mediate the relationship between both constructs. It is concluded that craving does not have an impact on the relationship between impulsivity and trait aggression in this patient sample.

Schnoll RA; Subramanian S; Martinez E; Engstrom PF. Correlates of continued tobacco use and intention to quit smoking among Russian cancer patients. International Journal of Behavioral Medicine 18(4): 325-332, 2011. (43 refs.)

Tobacco use among cancer patients is associated with adverse health outcomes. Little attention has been paid to tobacco use among cancer patients in developing countries, including Russia, where tobacco use is extremely high, and there is little public health infrastructure to address this issue. This study examined medical, socio-demographic, and psychological correlates of smoking status and intention to quit smoking among newly diagnosed Russian cancer patients. A cross-sectional study was conducted with 294 current or former smokers newly diagnosed with cancer. Compared with patients who quit smoking, patients who continued to smoke were more likely to report urges to smoke to satisfy positive reinforcing aspects of tobacco use. Compared with patients who were smoking and reported no intention to quit smoking in the next 3 months, patients who were smoking but intended to quit smoking reported higher levels of perceived risks associated with continued smoking and higher levels of self-efficacy to quit smoking. As commitment to developing smoking cessation treatment programs for cancer patients in Russia emerges, these data can help guide the development of behavioral interventions to assist patients with quitting smoking, enhancing their chances for improved clinical outcomes.

Schuck K; Otten R; Engels R; Kleinjan M. The relative role of nicotine dependence and smoking-related cognitions in adolescents' process of smoking cessation. Psychology & Health 26(10): 1310-1326, 2011

The present study evaluates the role of distinct components of nicotine dependence (craving, withdrawal, behavioural dependence) in comparison to smoking-related cognitions (attitudes, perceived social approval, self-efficacy) in adolescent smoking cessation. In the process towards smoking cessation, we distinguish between distinct behavioural transitions, respectively, short-term abstinence, reduction in smoking behaviour and prolonged cessation, to evaluate differences in cessation-related antecedents as a function of varying behavioural outcomes. A total of 850 adolescent smokers (age 14-16) participated in the present study. Smoking behaviour was assessed 1 year after baseline. Results showed that all dependence components had a distinct role in the prediction of behavioural change towards cessation. Furthermore, each behavioural transition was predicted by a distinct set of variables, indicating that contributions of cessation-related factors vary across the course towards cessation. Overall, our findings suggest that smoking-related cognitions are particularly relevant in the initiation of behavioural change, such as short-term abstinence, whereas nicotine dependence, craving in particular, becomes increasingly important in the prediction of maintained behavioural change, such as prolonged cessation. Implications encompass enhanced attention to the multidimensional nature of nicotine dependence and the value of comparing different behavioural outcomes in a comprehensive understanding of cessation-related factors.

Scott D; Hiroi N. Deconstructing craving: Dissociable cortical control of cue reactivity in nicotine addiction. Biological Psychiatry 69(11): 1052- 1059, 2011. (88 refs.)

Background: Cue reactivity, the ability of cues associated with addictive substances to induce seeking and withdrawal, is a major contributor to addiction. Although human imaging studies show that cigarette-associated cues simultaneously activate the insula and the orbitofrontal cortex and evoke craving, how these activities functionally contribute to distinct elements of cue reactivity remains unclear. Moreover, it remains unclear whether the simultaneous activation of these cortical regions reflects coordinated functional connectivity or parallel processing. Methods: We selectively lesioned the insula or orbitofrontal cortex with the excitotoxin ibotenic acid in mice, and their approach to nicotine-associated cues (n = 6-13/group) and avoidance of withdrawal-associated cues (n = 5-12/group) were separately examined in place conditioning paradigms. We additionally tested the role of these two cortical structures in approach to food-associated cues (n = 6-7/group) and avoidance of lithium chloride-associated cues (n = 6-7/group). Results: Our data show a double dissociation in which excitotoxic lesions of the insula and orbitofrontal cortex selectively disrupted nicotine-induced cue approach and withdrawal-induced cue avoidance, respectively. These effects were not entirely generalized to approach to food-associated cues or avoidance of lithium chloride-associated cues. Conclusions: Our data provide functional evidence that cue reactivity seen in addiction includes unique neuroanatomically dissociable elements and suggest that the simultaneous activation of these two cortical regions in response to smoking-related cues does not necessarily indicate functional connectivity.

Shadel WG; Martino SC; Setodji C; Cervone D; Witkiewitz K; Beckjord EB et al. Lapse-induced surges in craving influence relapse in adult smokers: An experimental investigation. Health Psychology 30(5): 588-596, 2011. (46 refs.)

Objectives: Nearly all smokers who lapse experience a full-blown relapse, but the mediating mechanisms that contribute to this relationship are not well understood. A better understanding of these mechanisms would help to advance more effective relapse prevention treatments for smokers. The purpose of this study is to experimentally evaluate the effects of a programmed smoking lapse on smoking relapse and the effects of postlapse changes in craving on relapse. Method: Adult smokers (n = 63) who quit smoking with a brief cognitive behavioral intervention and self-help materials were randomly assigned to one of two experimental conditions after 48 h of abstinence: No lapse (a no-smoking control/30-min waiting period) or lapse (smoking two cigarettes of their favored brand during a 30-min period). All participants were then followed daily for 14 days. Craving and biochemically verified self-reported abstinence were assessed on each follow-up day. Time (days) to relapse (7 consecutive days of smoking) was the main dependent measure. Results: Results of Cox regression analysis revealed that participants in the lapse condition relapsed more quickly than participants in the no-lapse condition (hazard ratio [HR] = 2.12, 95% confidence interval [Cl] = [1.03, 4.35]). These effects were attributable, in part, to episodic increases in craving among participants in the lapse condition only (HR = 12.42, 95% Cl =[2.00, 77.1]). Conclusions: Previously abstinent smokers who lapse are at risk for increased cigarette cravings and consequently, full-blown relapse. These results have implications for both cognitive behavioral treatments for relapse prevention and for medications designed to help smokers manage cravings.

Shmulewitz D; Keyes KM; Wall MM; Aharonovich E; Aivadyan C; Greenstein E et al. Nicotine dependence, abuse and craving: Dimensionality in an Israeli sample. Addiction 106(9): 1675-1686, 2011. (67 refs.)

Aims: Evidence-based changes planned for Diagnostic and Statistical Manual 5th edition (DSM-5) substance use disorders (SUDs) include combining dependence and three of the abuse criteria into one disorder and adding a criterion indicating craving. Because DSM-IV did not include a category for nicotine abuse, little empirical support is available for aligning the nicotine use disorder criteria with the DSM-5 criteria for other SUDs. Design: Latent variable analyses, bootstrap tests and likelihood ratio tests were used to explore the unidimensionality, psychometric properties and information of the nicotine criteria. Setting and participants A sample of household residents selected from the Israeli population register yielded 727 life-time cigarette smokers. Measurements: DSM-IV nicotine dependence criteria and proposed abuse and craving criteria, assessed with a structured interview. Findings: Three abuse criteria (hazardous use, social/interpersonal problems and neglect roles) were prevalent among smokers, formed a unidimensional latent trait with nicotine dependence criteria, were intermixed with dependence criteria across the severity spectrum and significantly increased the diagnostic information over the dependence-only model. A craving criterion was shown to fit well with the other criteria. Conclusion: Similar to findings from research on other substances, nicotine dependence, abuse and craving criteria appear to derive from a common underlying dimension. The results support alignment of nicotine criteria with those for alcohol and drug use disorders in Diagnostic and Statistical Manual 5th edition.

Sidhpura N; Parsons LH. Endocannabinoid-mediated synaptic plasticity and addiction-related behavior. (review). Neuropharmacology 61(7, special issue): 1070-1087, 2011. (403 refs.)

Endogenous cannabinoids (eCBs) are retrograde messengers that provide feedback inhibition of both excitatory and inhibitory transmission in brain through the activation of presynaptic CBI receptors. Substantial evidence indicates that eCBs mediate various forms of short- and long-term plasticity in brain regions involved in the etiology of addiction. The present review provides an overview of the mechanisms through which eCBs mediate various forms of synaptic plasticity and discusses evidence that eCB-mediated plasticity is disrupted following exposure to a variety of abused substances that differ substantially in pharmacodynamic mechanism including alcohol, psychostimulants and cannabinoids. The possible involvement of dysregulated eCB signaling in maladaptive behaviors that evolve over long-term drug exposure is also discussed, with a particular focus on altered behavioral responses to drug exposure, deficient extinction of drug-related memories, increased drug craving and relapse, heightened stress sensitivity and persistent affective disruption (anxiety and depression).

Sinha R; Shaham Y; Heilig M. Translational and reverse translational research on the role of stress in drug craving and relapse. (review). Psychopharmacology 218(1, special issue): 69-82, 2011. (201 refs.)

High relapse rates during abstinence are a pervasive problem in drug addiction treatment. Relapse is often associated with stress exposure, which can provoke a subjective state of drug craving that can also be demonstrated under controlled laboratory conditions. Stress-induced relapse and craving in humans can be modeled in mice, rats, and monkeys using a reinstatement model in which drug-taking behaviors are extinguished and then reinstated by acute exposure to certain stressors. Studies using the reinstatement model in rats have identified the role of several neurotransmitters and brain sites in stress-induced reinstatement of drug seeking, but the degree to which these preclinical findings are relevant to the human condition is largely unknown. Here, we address this topic by discussing recent results on the effect of alpha-2 adrenoceptors and substance P-NK1 receptor antagonists on stress-induced reinstatement in mice and rats and stress-induced craving and potentially stress-induced relapse in humans. We also discuss brain sites and circuits involved in stress-induced reinstatement of drug seeking in rats and those activated during stress-induced craving in humans. There is evidence that alpha-2 adrenoceptor agonists and NK1 receptor antagonists decrease stress-induced drug seeking in rats and stress-induced craving in humans. Whether these drugs would also prevent stress-induced drug relapse in humans and whether similar or different brain mechanisms are involved in stress-induced reinstatement in non-humans and stress-induced drug craving and relapse in humans are subjects for future research.

Tagmat D; Wolff J; Schumann A; John U; Thyrian JR. Development and psychometric properties of a short Situational Urge to Smoke Scale (SUS) for smoking adolescents. Substance Use & Misuse 46(8): 959-968, 2011. (34 refs.)

As urges are associated with positive-social, negative-affective, and habitual situations, we developed a sound scale to assess urges in these situations. In Northeastern Germany in 2005/2006, a sample of 1,093 smoking adolescents from 7th to 10th grade, aged 12-18 years, was used. Reliability analysis and exploratory and confirmatory factor analyses were applied. A three-factorial structure of the final situational urge to smoke scale (SUS) was found. Internal consistency of the scale was high (alpha = .89). The SUS is a new internally consistent scale that assesses the urge to smoke in adolescents. Further research needs to examine its predictive validity. The study's limitations are noted.

Tidey JW; Rohsenow DJ; Kaplan GB; Swift RM; Reid N. Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia. Psychopharmacology 217(2): 279-287, 2011. (61 refs.)

Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions. This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia. Using a double-blind, placebo-controlled, between-groups design, 57 non-treatment-seeking participants were randomized to receive 300 mg/day bupropion or placebo. One week later, participants were randomized to a contingency management (CM) intervention in which reductions in urinary cotinine levels were reinforced, or a non-contingent reinforcement (NR) condition in which session attendance was reinforced, regardless of cotinine level. Over the 22-day study period, participants visited the laboratory approximately three times per week to provide urine samples for analysis of cotinine levels, to give breath samples for analysis of carbon monoxide (CO) levels, and to report number of cigarettes smoked per day, nicotine withdrawal symptoms, cigarette craving, and psychiatric symptoms. Cotinine and CO levels significantly decreased during the study period in participants randomized to the CM condition, but not the NR condition. Bupropion did not reduce cotinine levels or increase the efficacy of CM. Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups. The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia.

Traylor AC; Parrish DE; Copp HL; Bordnick PS. Using virtual reality to investigate complex and contextual cue reactivity in nicotine dependent problem drinkers. Addictive Behaviors 36(11): 1068-1075, 2011. (33 refs.)

Alcohol and cigarette smoking frequently co-occur among adults in the U.S., resulting in a myriad of deleterious health outcomes. Cue reactivity has been posited as one factor that precludes individuals from overcoming alcohol and nicotine dependency. While cue reactivity studies have focused on the impact of proximal cues on cue reactivity, much less is known about the unique impact of complex and contextual cues. This pilot study compares nicotine and alcohol cue reactivity among a sample of nicotine dependent, daily drinkers (N=21) across neutral, party, and office courtyard virtual reality (VR) contexts embedded with proximal smoking cues to: 1) explore and compare the effects of complex nicotine cues on alcohol cross-cue reactivity between nicotine/alcohol dependent drinkers and nicotine dependent/non-alcohol dependent daily drinkers, and 2) assess the effectiveness of VR for eliciting cue-induced nicotine craving responses using complex nicotine cues. Nicotine dependent/non-alcohol dependent drinkers had significantly lower craving for alcohol in the non-alcohol congruent office courtyard VR scene and there was no difference in the alcohol-congruent party scene when compared to the alcohol dependent group, suggesting that the non-alcohol dependent daily drinking group was more likely to react to contextual cues. Consistent with prior cue reactivity studies, dependent smokers experienced significantly higher craving for nicotine in the VR smoking congruent contexts compared to the neutral contexts; however, nicotine/alcohol dependent participants did not return to baseline craving after exposure to smoking cues. These results suggest substantive differences in the ways that nicotine-dependent, daily alcohol drinkers and nicotine/alcohol dependent drinkers experience craving, whether cross-cue or traditional.

Ursprung WWSA; Morello P; Gershenson B; DiFranza JR. Development of a measure of the latency to needing a cigarette. Journal of Adolescent Health 48(4): 338-343, 2011. (18 refs.)

Purpose: People addicted to smoking experience a recurrent physiologic need to smoke anytime when they go too long without smoking. Our purpose was to evaluate the reliability and concurrent validity of a measure of the time elapsed between completion of smoking one cigarette and experiencing the need to smoke another (the latency to needing a cigarette-LTNC). We also investigated the relationship between the LTNC and dependence-related symptoms. Methods: An anonymous, self-administered survey was completed by 134 current adolescent smokers, and in a separate study, 32 smokers were asked to complete a retest. Results: A frequent need to smoke was reported by 84.3% of the current smokers. Consistent with published case histories, the duration of the LTNC varied widely between the individuals. Among subjects who reported a regular need to smoke, 48% reported that their LTNC had shortened over time. The median LTNC among subjects who had smoked < 100 cigarettes was 243 hours as compared with 2 hours for those who had smoked >= 100 cigarettes (p < .001). Test-retest reliability was reported to be excellent (r = .85, p < .001). As expected, LTNC correlated moderately and inversely with daily cigarette consumption (rho = -.53, p < .001). It also correlated inversely with cue-induced craving (rho = -.64, p < .001), psychological reliance on cigarettes (rho = -.43, p < .001), nicotine withdrawal (rho = -.57, p < .001), and pleasure obtained from smoking (rho = -.39, p < .001). Conclusion: The data obtained in this study support the reliability and concurrent validity of the LTNC measure.

Ussher M; Aveyard P; Reid F; West R; Evans P; Clow A et al. A randomised placebo-controlled trial of oral hydrocortisone for treating tobacco withdrawal symptoms. Psychopharmacology 216(1): 43-51, 2011. (51 refs.)

Rationale Many smokers experience a decline in cortisol to sub-normal levels during the first days of smoking cessation. A greater decline in cortisol is associated with more intense cigarette withdrawal symptoms, urge to smoke and relapse to smoking. Findings from an uncontrolled study suggest that glucocorticoids could ameliorate cigarette withdrawal. Objectives We investigated whether taking oral hydrocortisone would reduce withdrawal symptoms and the desire to smoke on the first day of temporary smoking abstinence compared with placebo. Methods. Using a double-blind within-subject randomised crossover design, 48 smokers took a single dose of 40 mg hydrocortisone, 20 mg hydrocortisone or placebo following overnight smoking abstinence. Abstinence was maintained through the afternoon, and withdrawal symptoms and the desire to smoke were rated across the morning. Salivary cortisol was assessed in the afternoon prior to abstinence ( baseline) and while abstinent after each treatment. Results. There was a significant dose-response relation between dose of hydrocortisone and reduction in depression and anxiety ratings while abstinent, but there were no other statistically significant associations with dose. Overall, the decline in cortisol following smoking cessation ( placebo only) was not significant. Cortisol level on the afternoon of smoking abstinence was not significantly associated with symptom ratings. Conclusions. Supplements of hydrocortisone do not reduce the desire to smoke but may ameliorate withdrawal-related depression and anxiety, although the clinical benefit is slight.

Veeneman MMJ; Broekhoven MH; Damsteegt R; Vanderschuren LJMJ. Distinct contributions of dopamine in the dorsolateral striatum and nucleus accumbens shell to the reinforcing properties of cocaine. Neuropsychopharmacology 37(2): 487-498, 2012. (79 refs.)

Dopaminergic neurotransmission in the dorsal and ventral striatum is thought to be involved in distinct aspects of cocaine addiction. Ventral striatal dopamine mediates the acute reinforcing properties of cocaine, whereas dopamine in the dorsolateral striatum (DLS) is thought to become involved in later stages of the addiction process to mediate well-established cue-controlled drug seeking. However, it is unclear whether the DLS also has a role in the reinforcing properties of cocaine itself. Therefore, we systematically investigated the involvement of dopamine in dorsal and ventral striatal regions in cocaine self-administration, using various schedules of reinforcement in animals with limited drug taking experience. Intra-DLS infusion of the dopamine receptor antagonist alpha-flupenthixol did not affect the acquisition of cocaine self-administration, increased cocaine self-administration under a fixed ratio-1 (FR-1) schedule of reinforcement, caused a rightward and downward shift of the dose-response curve of cocaine under an FR-1 schedule of reinforcement and decreased responding for cocaine under a progressive ratio (PR) schedule of reinforcement. Infusion of alpha-flupenthixol into the ventral nucleus accumbens (NAcc) shell inhibited the acquisition of cocaine self-administration, reduced responding for the drug under FR-1 and PR schedules of reinforcement, and caused a downward shift of the dose-response curve of cocaine self-administration under an FR-1 schedule of reinforcement. These data show that dopamine in both the DLS and NAcc shell is involved in cocaine reinforcement. We suggest that the DLS and the NAcc shell mediate somewhat distinct facets of the reinforcing properties of cocaine, related to its rewarding and motivational aspects, respectively.

Vollstadt-Klein S; Loeber S; Winter S; Lemenager T; von der Goltz C; Dinter C et al. Attention shift towards smoking cues relates to severity of dependence, smoking behavior and breath carbon monoxide. European Addiction Research 17(4): 217- 224, 2011. (32 refs.)

The aim of this study was to assess the severity of dependence as a factor affecting the attentional bias of smokers towards smoking-related stimuli and to clarify contradictory results of previous studies. A visual dot probe task was administered to 51 smokers and 41 nonsmokers to assess the attentional bias. Smokers were classified into a group of less severely dependent and a group of more severely dependent smokers according to the Fagerstrom Test for Nicotine Dependence, the number of cigarettes smoked per day or the CO concentration in the expired air. Nicotine craving was assessed as well. The more severely dependent smokers displayed an attentional bias towards smoking-related stimuli, while smokers with less severe nicotine dependence showed a negative attentional bias which was also observed in nonsmokers. A multiple linear regression indicated that CO concentration was the only significant predictor of attentional bias. In the total group of smokers we found a positive association between attentional bias and craving for the rewarding effects of nicotine. Future studies are warranted to further enhance our understanding of factors that affect attentional bias as appetitive responses towards smoking- related stimuli might be an important target for therapeutic interventions.

Wang W; Li QA; Wang YR; Tian J; Yang WC; Li W et al. Brain fMRI and craving response to heroin-related cues in patients on methadone maintenance treatment. American Journal of Drug and Alcohol Abuse 37(2): 123-130, 2011. (57 refs.)

Objective: To investigate the subjective craving and brain response to heroin-related cues in former heroin addicts on long-term methadone maintenance treatment. Methods: Fourteen participants completed an event-related functional magnetic resonance imaging task including heroin-related and nonheroin-related (neutral) cues. Craving self-reports were collected before and after the task. Results: Although no significant craving changes were associated with the task, blood oxygen-level dependence intensity was significantly greater during exposure to heroin-related cues, compared to neutral cues in brain areas studied. Conclusions and Scientific Significance: The results indicate that the learned brain response of former heroin addicts to drug-related stimuli may persist despite long-term methadone maintenance treatment.

Wilcox CE; Teshiba TM; Merideth F; Ling J; Mayer AR. Enhanced cue reactivity and fronto-striatal functional connectivity in cocaine use disorders. Drug and Alcohol Dependence 115(1-2): 137- 144, 2011. (67 refs.)

Chronic cocaine use is associated with enhanced cue reactivity to drug stimuli. However, it may also alter functional connectivity (fcMRI) in regions involved in processing drug stimuli. Our aims were to evaluate the neural regions involved in subjective craving and how fcMRI may be altered in chronic cocaine users. Fourteen patients with a confirmed diagnosis of cocaine abuse or dependence (CCA) and 16 gender, age, and education-matched healthy controls (HC) completed a cue reactivity task and a resting state scan while undergoing functional magnetic resonance imaging. CCA showed increased activation compared to HC in left dorsolateral prefrontal and bilateral occipital cortex in response to cocaine cues but not to appetitive control stimuli. Moreover. CCA also showed increased activation within the orbital frontal cortex (OFC) for cocaine cues relative to the appetitive stimuli during a hierarchical regression analysis. A negative association between subjective craving and activity in medial posterior cingulate gyrus (PCC) was also observed for CCA. CCA exhibited increased resting state correlation (positive) between cue-processing seed regions (OFC and ventral striatum), and negative connectivity between cue-processing regions and PCC/precuneus. These alterations in fcMRI may partially explain the neural basis of increased drug cue salience in CCA.

Wise PM; Preti G; Eades J; Wysocki CJ. The effect of menthol vapor on nasal sensitivity to chemical irritation. Nicotine & Tobacco Research 13(10): 989-997, 2011. (57 refs.)

Introduction: Among other effects, menthol added to cigarettes may modulate sensory response to cigarette smoke either by masking "harshness" or contributing to a desirable "impact." However, harshness and impact have been imprecisely defined and assessed using subjective measures. Thus, the current experiments used an objective measure of sensitivity to chemical irritation in the nose to test the hypothesis that menthol vapor modulates sensitivity to chemical irritation in the airways. Methods: Nasal irritation thresholds were measured for 2 model compounds (acetic acid and allyl isothiocyanate) using nasal lateralization. In this technique, participants simultaneously sniff clean air in one nostril and chemical vapor in the other and attempt to identify the stimulated nostril. People cannot lateralize based on smell alone but can do so when chemicals are strong enough to feel. In one condition, participants were pretreated by sniffing menthol vapor. In a control condition, participants were pretreated by sniffing an odorless blank (within-subjects design). Results: Pretreatment with menthol vapor decreased sensitivity to nasal irritation from acetic acid (participants required higher concentrations to lateralize) but increased sensitivity to allyl isothiocyanate (lower concentrations were required). Conclusions: The current experiments provide objective evidence that menthol vapor can modulate sensitivity to chemical irritation in the upper airways in humans. Cigarette smoke is a complex mixture of chemicals and particulates, and further work will be needed to determine exactly how menthol modulates smoking sensation. A better understanding could lead to treatments tailored to help menthol smokers quit by replacing the sensation of mentholated cigarettes.

Zou ZL; Zhang JX; Huang XT; Weng XC. Impaired directed forgetting in abstinent heroin addicts. Memory 19(1): 36-44, 2011. (48 refs.)

Drug-related memories persist long into abstinence and are potent elicitors of drug craving and relapse. We report two experiments examining whether heroin-dependent individuals are impaired in intentionally suppressing drug-related memories. Experiment 1 adopted the Item paradigm where addicts and healthy controls were presented with a list of words each followed by a remember or forget cue. Experiment 2 adopted the List paradigm where they studied one list of items and were then split into a remember group and a forget group. Both groups studied a second list, except that the forget group was told to forget the first list. Compared with controls, addicts showed a reduced directed forgetting effect in the Item method and a total absence of one measure of directed forgetting in the List method (List 2 benefits). Results indicate that heroin addicts are impaired in directed forgetting and that the deficits are likely associated with memory encoding as opposed to retrieval. Possible problems include reduced ability in actively suppressing/stopping encoding of irrelevant information into memory or inability in changing/resetting encoding strategies. In neither experiment did the addicts show any differential directed forgetting effects between drug-related words and neutral words, indicating the generic nature of their intentional forgetting deficits.