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CORK Bibliography: Craving and Drugs

69 citations. March 2008 to present

Prepared: March 20089

Attwood AS; O'Sullivan H; Leonards U; Mackintosh B; Munafo MR. Attentional bias training and cue reactivity in cigarette smokers. Addiction 103(11): 1875-1882, 2008. (35 refs.)

Aims: Attentional bias for drug-related cues has been associated with drug maintenance and relapse. We investigated whether attentional bias for smoking-related stimuli could be altered using a modified visual probe task in cigarette smokers. We also sought to determine whether changes in attentional bias were associated with changes in subsequent craving and cue reactivity. Participants: Male and female (n = 54) current smokers (>= 5 cigarettes per day), aged between 18 and 40 years, were recruited from staff and students of the University of Bristol, and from the general population. Design: Participants attended a single test session and completed an attentional training procedure in which they were either trained to attend to smoking-related pictorial stimuli (attend group) or to neutral pictorial stimuli (avoid group). Group allocation was randomized. Measurements: Following attentional training, participants underwent a smoking cue exposure procedure in which they were exposed to smoking-related stimuli. Subjective measures of mood and craving were taken at baseline and before and after cue exposure. Participants then smoked a cigarette and smoking topography was measured. Findings: Attentional training increased attentional bias among participants in the attend group, and decreased attentional bias among those in the avoid group. There were also differences between the attend and avoid groups in post-training changes in craving during exposure to in vivo smoking cues, reflecting greater increases in craving in the attend group, although these effects were observed in males only. Conclusions: These data are the first to show alterations in attentional bias for smoking-related stimuli following a modified visual probe training procedure. Furthermore, post-training group differences in subjective craving suggest potential clinical utility of training procedures, although these effects may operate only in males. Future research should investigate whether multiple training sessions enhance post-training reductions in craving and cue reactivity, and the longer-term persistence of training effects.

Barr AM; Procyshyn RM; Hui P; Johnson JL; Honer WG. Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment. Schizophrenia Research 100(1-3): 252-260, 2008. (53 refs.)

Purpose: The prevalence of smoking in schizophrenia has reliably been reported as being higher than for any other psychiatric disorder. While a number of theories have been proposed to account for such high rates of smoking, little is known about the subjective motivation for why schizophrenia patients smoke in comparison with those without the disease. Objectives: The aim of the present study was to evaluate and compare smoking motivation in control subjects and schizophrenia patients, and determine if factors such as type of medication or access to cigarettes could contribute to self-reported motivation for smoking. Methods: We assessed motivation to smoke in 61 schizophrenia inpatients and 33 non-psychiatric health worker controls at a tertiary care psychiatric facility in a cross-sectional study. Nicotine dependency and smoking behavior were evaluated using the Fagerstrom Test for Nicotine Dependence and a validated questionnaire that assesses motivation for smoking along seven different dimensions. Results: Schizophrenia patients reported a stronger motivation to smoke than controls for reasons related to pleasure from the act of smoking, as well as a need for psychomotor stimulation. Scores on both these factors were significantly associated with daily antipsychotic drug dose. The sedative and anxiolytic effects of smoking were related to anticholinergic load of psychiatric medications. Conclusion: The findings highlight important differences in self-reported motivation to smoke between schizophrenia patients and normals. Antipsychotic drugs may also influence aspects of motivation to smoke.

Bonnet U; Harkener J; Scherbaum N. A case report of propofol dependence in a physician. Journal of Psychoactive Drugs 40(2): 215-217, 2008. (20 refs.)

Propofol is a widely used general anaesthetic with multisite mechanisms and especially ultrashort activation of certain central GABA-A receptors. Since its introduction into the market in the mid 1980s this is the seventh report on propofol dependence in the literature. The present case shows for the first time that craving for propofol can be quite intense and able to induce addictive behaviour.

Carpenter MJ; Saladin ME; Leinbach AS; Larowe SD; Upadhyaya HP. Menstrual phase effects on smoking cessation: A pilot feasibility study. Journal of Women's Health 17(2): 293-301, 2008. (30 refs.)

Background and Objectives: A growing body of research suggests that nicotine withdrawal and cigarette craving may vary across the menstrual cycle and that the luteal phase of the cycle may be associated with increases in each. This potential relationship suggests that careful timing of quit attempts during the menstrual cycle may improve initial success at abstinence, although there are no direct tests of this approach yet published. Our objectives were to preliminarily test the effect of timing of quit attempts for smoking cessation relative to menstrual cycle and to identify methodological procedures that could guide subsequent, larger clinical trials. Methods: In this pilot study, we randomized female smokers aged 18 - 40 who were not currently using hormonal contraception to quit smoking during either the follicular ( n = 25) or luteal phase (n = 19) of their menstrual cycle. Participants were provided with two sessions of smoking cessation counseling (90 minutes total). All participants were provided with a transdermal nicotine patch contingent on maintenance of abstinence throughout the course of the 6-week study. Results: Among participants who initiated treatment, received the patch, and made a quit attempt (n = 35), carbon monoxide-verified repeated point prevalence abstinence 2 weeks after the target quit date was higher in the follicular than the luteal group (32% vs. 19%, respectively; OR = 2.0, 95% CI = 0.4- 9.8). Within the overall study population, this difference was slightly lower (24% vs. 16%; OR = 1.7, 95% CI = 0.4- 7.8). Conclusions: Timing quit attempts based on menstrual phase is feasible. Insights gained from this study and the recommendations made herein may inform future research on this important clinical question.

Carter BL; Bordnick P; Taylor A; Day SX; Paris M. Location and longing: The nicotine craving experience in virtual reality. Drug and Alcohol Dependence 95(1/2): 73-80, 2008. (30 refs.)

Considerable research suggests that cigarette craving is complex, with psychological, emotional, cognitive, and behavioral aspects that are inadequately captured by typical craving assessments that focus on level of severity. That is, the experience of craving, for cigarette smokers, remains poorly understood. This study immersed smokers in different virtual reality (VR) scenarios (with and without cigarette cues present), collected detailed craving assessments, and analyzed the data using a multidimensional analytic approach. Non-treatment-seeking, nicotine dependent smokers (N = 22) experienced two different virtual reality scenarios, one with cigarette cues and one without, and rated 24 descriptors related to craving. Multidimensional scaling (MIDS) models demonstrate that smokers' experience of craving is qualitatively, structurally different under VR smoking cue conditions versus neutral conditions. This finding sheds new light on the complexity of craving as well as implications for its measurement.

Carter BL; Lam CY; Robinson JD; Paris MM; Waters AJ; Wetter DW; Cinciripini PM. Real-time craving and mood assessments before and after smoking. Nicotine & Tobacco Research 10(7): 1165-1169, 2008. (23 refs.)

This study explored some quandaries concerning craving and mood as motivators to smoke. Craving and negative mood have long been associated with day-to-day smoking as two of the primary motivational forces behind the maintenance of the behavior, as well as significant barriers in smokers' attempts to quit. Craving remains a clinically relevant phenomenon, with most smokers describing craving as a troublesome problem when quitting. Smokers' self-reports of negative mood, as an antecedent for smoking, are so robustly reported that many models of nicotine dependence have incorporated a critical role for negative mood in maintaining smoking behavior. However, several naturalistic studies that collected mood ratings with hand held computers from smokers in real time, just before smoking a cigarette, have provided scant evidence that negative mood plays a major role in motivation to smoke. No study to date has examined craving and mood data as a consequence of smoking, that is, collecting the same data immediately after smoking. This study used personal digital assistants (PDAs) to collect craving and mood data immediately before smoking, immediately after smoking, and at random times of day. Nontreatment seeking smokers (N=72) carried a PDA for an average of 10 days while they recorded their smoking behavior. Results showed that craving and negative mood ratings were lowest immediately after smoking compared with immediately before smoking and at random times of day. These findings suggest that smokers may be at least partially motivated to smoke to lower their craving and improve their mood states.

Chong J; Lopez D. Predictors of relapse for American Indian women after substance abuse treatment. American Indian and Alaska Native Mental Health Research 14(3): 24-48, 2008. (58 refs.)

The objective of this study was to describe the predictors of substance use relapse of American Indian (AI) women up to one year following substance abuse treatment. Relapse is defined as any use of alcohol or drugs in the past 30 days at the follow-up points. Data were collected from AI women in a 45-day residential substance abuse treatment program. Predictors include distal (in time) proximal (recent), and intrapersonal factors. Results indicated that intrapersonal factors showed the strongest relationship with relapse, followed by proximal and distal factors. Negative messages about using alcohol or drugs from the client's father while growing up may have had an impact on whether the client used alcohol at 6 months. Conflicts with other people and being in the company of alcohol or drug users were highly predictive of relapse. While craving was highly predictive of substance use at follow up, self-efficacy was highly predictive of no substance use. Knowledge about predictors of relapse among this population should be used as a guide toward individual treatment planning.

DiFranza JR; Ursprung WWSA. The latency to the onset of nicotine withdrawal: A test of the sensitization-homeostasis theory. Addictive Behaviors 33(9): 1148-1153, 2008. (42 refs.)

The latency to withdrawal (LTW) is the expired time between the last cigarette and when the smoker feels the need to smoke again. The sensitization-homeostasis theory predicts that the LTW is inversely related to the frequency and duration of smoking such that more frequent cigarette consumption and a longer history of tobacco use will be associated with a shorter LTW. An anonymous cross-sectional survey of 1055 10th and 11th grade students of mixed ethnicity was conducted in two schools using self-completed questionnaires. Participants were asked "After you have smoked a cigarette, how long can you go before you feel you need to smoke again?" Of 162 current smokers, 73.5% reported a regular need to smoke and a LTW. Reported values for the LTW ranged from .05 h to "3 weeks or more." Monthly cigarette consumption ranged from I to 895, The LTW correlated inversely with monthly cigarette consumption (Kendall's tau b = -.53, P<.001) and the duration of smoking (Kendall's tau b = -.25, P<.001) as predicted by the sensitization-homeostasis theory.

Ditre JW; Brandon TH. Pain as a motivator of smoking: Effects, of pain induction on smoking urge and behavior. Journal of Abnormal Psychology 117(2): 467-472, 2008. (27 refs.)

Tobacco smoking has been associated with the development and exacerbation of chronically painful conditions. Conversely, there is reason to believe that smokers may be motivated to use tobacco as a means of coping with their pain. To date, no controlled, experimental studies have tested for a causal relationship between pain and smoking motivation. The primary aim of the current study was to test the hypothesis that laboratory-induced cold pressor pain would enhance smoking motivation, as measured by self-reported urge to smoke and observation of immediate smoking behavior. Smokers (N = 132) were randomly assigned to either pain or no pain conditions. Results indicated that situational pain increased urge ratings and produced shorter latencies to smoke. The relationship between pain and increased urge to smoke was partially mediated by pain-induced negative affect. The relationship between pain and shorter latency to smoke was fully mediated by pain-induced urge to smoke. This study provides the 1st experimental evidence that situational pain can be a potent motivator of smoking.

Doran N; McChargue D; Spring B. Effect of impulsivity on cardiovascular and subjective reactivity to smoking cues. Addictive Behaviors 33(1): 167-172, 2008. (17 refs.)

Individuals with high levels of impulsivity are more likely to smoke and may have greater difficulty quitting than other smokers. Although the specific mechanisms mediating this relationship are not explicitly known, one candidate is disproportionate cigarette craving in response to environmental smoking cues. We assessed the effect of impulsivity on three measures of cue reactivity. Regular smokers (n=75) were exposed to a smoking cue and a neutral cue in 2 counterbalanced experimental sessions. Cigarette craving, heart rate (HR), and mean arterial pressure (MAP) were used to index cue reactivity. More impulsive smokers exhibited a disproportionate response to the smoking cue in terms of MAP (p=.009) but not HR or craving. Impulsive smokers may experience disproportionate cigarette craving in response to environmental smoking cues that are not reflected in self-report measures due to a relative lack of conscious awareness of the urge to smoke.

Farren CK; Mc Elroy S. Treatment response of bipolar and unipolar alcoholics to an inpatient dual diagnosis program. Journal of Affective Disorders 106(3): 265-272, 2008. (33 refs.)

Background: Depressed and bipolar alcoholics represent a significant affective subgroup that has a poorer prognosis than either diagnosis alone. To date few systematic treatment programs have been developed to treat dual diagnosis. Methods: An inpatient treatment program was developed at St Patrick's Hospital Dublin to treat dual diagnosis clients with alcohol dependence and either unipolar or bipolar affective disorder. Clients (N=232) were assessed for depression, anxiety, elation, cravings, drink and drug intake on admission, discharge, 3 and 6 months post-discharge from the program. Results: In the overall group there was a reduction in number of drinking days and units per drinking day over the study (P <.01). There was a 71.8% complete abstinent rate at 3 months and 55.8% at 6 months in the depression group, non-significantly greater than for the bipolar group at 64.7% and 54.1% respectively. Gamma GT, MCV and craving scores were significantly reduced over time (p <.01). Mania, depression and anxiety inventory scores fell over time in both groups (p <.01). 15-21-year olds were more severely anxious, had higher illicit drug use, and were more likely to relapse to drug use than older clients. Bipolar 1 clients were significantly more likely than bipolar 2 clients to be on mood stabilisers at all follow-up stages (p <.001). Limitations: No control group was used. Conclusions: There is evidence for efficacy of a specifically designed dual diagnosis inpatient treatment prograrn as both depressed and bipolar alcoholics had significant reductions in all measurements of mood, craving, and alcohol/drug consumption by self report and biological markers, suggesting both diagnoses can be effectively treated together.

Field M; Cox WM. Attentional bias in addictive behaviors: A review of its development, causes, and consequences. (review). Drug and Alcohol Dependence 97(1-2): 1-20, 2008. (161 refs.)

A wealth of research from the past two decades shows that addictive behaviors are characterized by attentional biases for substance-related stimuli. We review the relevant evidence and present an integration of existing theoretical models to explain the development, causes, and consequences of addiction-related attentional biases. We suggest that through classical conditioning, substance-related stimuli elicit the expectancy of substance availability, and this expectancy causes both attentional bias for substance-related stimuli and subjective craving. Furthermore, attentional bias and craving have a mutual excitatory relationship such that increases in one lead to increases in the other, a process that is likely to result in substance self-administration. Cognitive avoidance strategies, impulsivity, and impaired inhibitory control appear to influence the strength of attentional biases and subjective craving. However, some measures of attentional bias, particularly the addiction Stroop, might reflect multiple underlying processes, so results need to be interpreted cautiously. We make several predictions that require testing in future research, and we discuss implications for the treatment of addictive behaviors.

Flagel SB; Akil H; Robinson TE. Individual differences in the attribution of incentive salience to reward-related cues: Implications for addiction. (review). Neuropharmacology 56(Supplement 1): 139-148, 2009. (118 refs.)

Drugs of abuse acquire different degrees of control over thoughts and actions based not only on the effects of drugs themselves, but also on predispositions of the individual. Those individuals who become addicted are unable to shift their thoughts and actions away from drugs and drug-associated stimuli. Thus in addicts, exposure to places or things (cues) that has been previously associated with drug-taking often instigates renewed drug-taking. We and others have postulated that drug-associated cues acquire the ability to maintain and instigate drug-taking behavior in part because they acquire incentive motivational Properties through Pavlovian (stimulus-stimulus) learning. In the case of compulsive behavioral disorders, including addiction, such cues may be attributed with pathological incentive value ("incentive salience"). For this reason, we have recently begun to explore individual differences in the tendency to attribute incentive salience to Cues that predict rewards. When discrete cues are associated with the non-contingent delivery of food or drug rewards some animals come to quickly approach and engage the Cue even if it is located at a distance from where the reward will be delivered. In these animals the reward-predictive Cue itself becomes attractive, eliciting approach towards it, presumably because it is attributed with incentive salience. Animals that develop this type of conditional response are called "sign-trackers". Other animals, "goal-trackers", do not approach the reward-predictive cue, but upon cue presentation they immediately go to the location where food will be delivered (the "goal"). For goal-trackers the reward-predictive cue is not attractive, presumably because it is not attributed with incentive salience. We review here preliminary data Suggesting that these individual differences in the tendency to attribute incentive salience to cues predictive of reward may confer Vulnerability or resistance to compulsive behavioral disorders, including addiction. It will be important, therefore, to study how environmental, neurobiological and genetic interactions determine the extent to which individuals attribute incentive value to reward-predictive stimuli.

Florsheim P; Heavin S; Tiffany S; Colvin P; Hiraoka R. An experimental test of a craving management technique for adolescents in substance-abuse treatment. Journal of Youth and Adolescence 37(10): 1205-1215, 2008. (66 refs.)

This paper describes an experiment designed to test an imagery-based craving management technique with a sample of adolescents diagnosed with substance-use disorders. Seventy adolescents between the ages of 14 and 18 (41 males) were recruited through two substance-abuse treatment programs. The experimental procedure involved stimulating craving using a previously tested imagery technique and then administering a newly developed procedure for reducing craving. Participants were randomly assigned to one of three conditions: an "interpersonal help" craving reduction condition; an "interpersonal distracter" craving reduction condition; and a control condition in which craving was stimulated and allowed to attenuate naturally, without intervention. Results: indicated that following exposure to imagery-based drug cues, the "interpersonal distracter" condition effectively interrupted craving, compared to the control condition. The "interpersonal help condition" did not attenuate participant's craving response relative to the control condition. This study illustrates how experimental methods can be used to test and refine the efficacy of clinical interventions.

Florsheim P; Shiozaki T; Hiraoka R; Tiffany ST; Heavin S; Hall S et al. Craving among polysubstance using adolescents. Journal of Child & Adolescent Substance Abuse 17(2): 101-124, 2007. (65 refs.)

The phenomenon of drug craving among adolescents with substance use disorders has been largely overlooked by addiction researchers. This study was designed to: (1) assess craving among adolescents with polysubstance use disorders (SUDS); and (2) examine the association between personality traits and craving among adolescents with SUDS. Craving was found to be a multidimensional phenomenon that demonstrated some degree of consistency across substances (in this case, marijuana and alcohol). Selected personality traits were associated with distinct components of craving; for example, adolescent substance users who obtained high sensation-seeking scores tended to crave the excitement associated with drug use. Adolescents who obtained high anxious-neuroticism scores tended to crave the experience of distress relief associated with drug use.

Fortuna JL; Smelson DA. The phenomenon of drug craving. Journal of Psychoactive Drugs 40(3): 255-261, 2008. (67 refs.)

The phenomenology of drug craving has become the focus of much research within addictive disorders because of the belief that desire plays a role in maintaining the addiction. Many of the studies have focused on the activation of neural pathways, particularly within the dopamine system in response to specific events or stimuli. While many of these studies have focused on a particular drug of choice, little has been done across addictive disorders. This article will present and review phenomena that induce drug craving, as well as delineate precise neural pathways which are activated during craving and specific neurobiological markers which are associated with an increased risk for drug craving and other forms of addictive behavior.

Franken IHA; Dietvorst RC; Hesselmans M; Franzek EJ; de Wetering BJMV; Van Strien JW. Cocaine craving is associated with electrophysiological brain responses to cocaine-related stimuli. Addiction Biology 13(3/4): 386-392, 2008. (28 refs.)

Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.

Gray KM; LaRowe SD; Upadhyaya HP. Cue reactivity in young marijuana smokers: A preliminary investigation. Psychology of Addictive Behaviors 22(4): 582-586, 2008. (28 refs.)

To develop and evaluate the feasibility of a cue reactivity paradigm for young marijuana smokers, the authors set up a laboratory procedure involving neutral and marijuana-related imagery, video, and in vivo cues. Fifteen adolescents and young adults with cannabis use disorders completed the procedure, which included continuous measurement of skin conductance and heart rate. Participants also completed questionnaires regarding marijuana craving before, during, and after cue presentations. Higher levels of craving and skin conductance were observed during marijuana cue presentations. The procedure appears to elicit cue reactivity among adolescents and young adults with cannabis use disorders and should be further evaluated and refined with a larger sample. Implications for future studies are discussed.

Gray N. Powerwalls prey on the susceptible. (editorial). Addiction 103(2): 329-330, 2008. (5 refs.)

Haughey HM; Marshall E; Schacht JP; Louis A; Hutchison KE. Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes. Addiction 103(10): 1678-1686, 2008. (51 refs.)

Aim To examine whether withdrawal after abstinence and cue-elicited craving were associated with polymorphisms within two genes involved in regulating the endocannabinoid system, cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH). Two single nucleotide polymorphisms (SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers. Participants Participants were 105 students at the University of Colorado, Boulder between the ages of 18 and 25 years who reported smoking marijuana daily Measurements Participants were assessed once at baseline and again after 5 days of abstinence, during which they were exposed to a cue-elicited craving paradigm. Outcome measures were withdrawal and craving collected using self-reported questionnaires. In addition, urine samples were collected at baseline and on day 5 for the purposes of 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THC-COOH) metabolite analysis. Findings Between the two sessions, THC-COOH metabolite levels decreased significantly, while measures of withdrawal and craving increased significantly. The CNR1 SNP displayed a significant abstinence x genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence x genotype interaction on craving. Conclusions: These genetic findings may have both etiological and treatment implications. However, longitudinal studies will be needed to clarify whether these genetic variations influence the trajectory of marijuana use/dependence. The identification of underlying genetic differences in phenotypes such as craving and withdrawal may aid genetically targeted approaches to the treatment of cannabis dependence.

Heishman SJ; Singleton EG; Pickworth WB. Reliability and validity of a short form of the tobacco craving questionnaire. Nicotine & Tobacco Research 10(4): 643-651, 2008. (42 refs.)

The Tobacco Craving Questionnaire (TCQ) is a valid and reliable 47-item self-report instrument that assesses tobacco craving in four dimensions: emotionality, expectancy, compulsivity, and purposefulness. For use in research and clinical settings, we constructed a 12-item version of the TCQ by selecting three items from each of the four factors that exhibited optimal within-factor reliability (Cronbach's alpha coefficient) and inter-item correlation. Smokers (N=196) completed the TCQ-Short Form (TCQ-SF) after overnight tobacco deprivation and on a separate day during ad libitum smoking. Confirmatory factor analyses indicated acceptable model fit for a 4-factor model, with congruence coefficients suggesting high to very high similarity in factor patterns and magnitude of factor loadings between the TCQ and TCQ-SF in both conditions. Scores on each factor were significantly greater after tobacco deprivation than ad libitum smoking, were associated with measures of tobacco withdrawal, and varied with degree of nicotine dependence. Cronbach's alpha coefficients and average inter-item correlations were similar in both conditions and were consistent with reliability values obtained in the initial validation of the TCQ. Test-retest correlation coefficients were also similar to those found in a previous study. These findings suggest that the TCQ-SF is as valid and reliable as the 47-item TCQ in measuring tobacco craving.

Ilgen M; Jain A; Kim HM; Trafton JA. The effect of stress on craving for methadone depends on the timing of last methadone dose. Behaviour Research and Therapy 46(10): 1170-1175, 2008. (42 refs.)

Background: This study examined the extent to which the timing of last methadone dose moderates the influence of a laboratory stressor on craving for methadone in a sample of methadone maintenance patients. Methods: Methadone maintenance patients (N = 41) completed a Computerized stress manipulation with two levels (low and high stress) on two separate days: (1) immediately following the administration of their standard daily methadone dose and (2) immediately prior to receiving their standard daily dose. The impact of stress, timing of methadone dose and their interaction were examined on self-report measures of stress and craving for methadone. Results: Craving ratings varied according to the timing of last methadone dose. Immediately following methadone dose (i.e., day 1, there was no effect for stress on craving (0.12; p = 0.30). However, prior to receiving methadone dose (i.e., day 2), the high stress effect on craving was significant (1.51; p < 0.001). Discussion: The present findings indicate that patients currently receiving methadone maintenance treatment may be particularly Vulnerable to stress-related relapse immediately prior to daily methadone dosing.

Kemps E; Tiggemann M. Competing visual and olfactory imagery tasks suppress craving for coffee. Experimental and Clinical Psychopharmacology 17(1): 43-50, 2009. (37 refs.)

Using the elaborated intrusion theory of desire as a theoretical basis, the present experiments investigated whether mutual competition between modality-specific tasks and desire-related imagery can suppress cravings for caffeine-in particular, coffee. Data from a pilot survey (Experiment 1) in 106 female undergraduate habitual coffee drinkers showed that coffee cravings are characterized predominantly by sensory images in the visual, olfactory, and gustatory modalities. Experiments 2 and 3 tested the prediction that a competing visual or olfactory imagery task would reduce such cravings, relative to an auditory imagery task. In each experiment, 90 female undergraduate habitual coffee drinkers were asked to forego their morning cup of coffee and were subsequently exposed to pictures of coffee (Experiment 2) or actual coffee (Experiment 3). After the craving induction protocol, participants completed either a visual, auditory, or olfactory imagery task with neutral (i.e., non-coffee-related) content. As predicted, the visual and olfactory imagery tasks reduced participants' cravings for coffee, whereas the auditory task did not. Imagery techniques in the visual or olfactory domain could provide a useful adjunct to the behavioral regime of caffeine fading for consumers who are trying to quit caffeine use or reduce their intake.

Kennedy A; Wood AE; Saxon AJ; Malte C; Harvey M; Jurik J et al. Quetiapine for the treatment of cocaine dependence - An open-label trial. Journal of Clinical Psychopharmacology 28(2): 221-224, 2008. (23 refs.)

The monaminergic properties of second generation antipsychotics are prompting research on their use to treat cocaine dependence, with inconclusive results to date. In preliminary reports, the atypical antipsychotic quetiapine has shown promise for the treatment of substance abuse disorders. The primary objective of the current study was to assess the efficacy of quetiapine in reducing cocaine cravings and use in nonpsychotic subjects with cocaine dependence over 6 weeks of open-label treatment. Twenty-two cocaine-dependent, nonpsychotic men were initiated to open-label treatment with quetiapine (300-600 mg/d). The primary outcome measure was weekly self-report of cocaine cravings as assessed with the Brief Substance Craving Scale. Cocaine use was captured with a self-report Timeline Follow-back calendar, administered every 2 weeks. Side effect monitoring was conducted weekly, and movement disorders were assessed every 2 weeks. Intent-to-treat regression analyses (n = 22) indicated that the Brief Substance Craving Scale total score decreased significantly overtime (P < 0.001). Self-reports also suggested decreased cocaine use. There was no treatment-related increase in movement disorders, and most side effects were mild. However, all subjects did experience sedation, and several subjects dropped out because of it. What is more, weight increased significantly over time (P < 0.001). Open-label quetiapine treatment reduced cravings and improved some aspects of cocaine dependence in nonpsychotic individuals. Additional research is needed to confirm the current findings and to further delineate the role quetiapine may play in the treatment of cocaine use disorders.

King A; Epstein A; Conrad M; McNamara P; Cao DC. Sex differences in the relationship between alcohol-associated smoking urge and behavior: A pilot study. American Journal on Addictions 17(5): 347-353, 2008. (53 refs.)

This study examined sex differences in alcohol-associated smoking urge and smoking patterns to elucidate factors contributing to the co-use of alcohol and cigarettes. Participants were 39 (22M, 17F) binge-drinking tobacco chippers. Although men and women showed similar alcohol-smoking patterns and similar alcohol-induced smoking urges, a positive association between these factors was observed only in men. The lack of relationship in women suggests that co-use of these substances may be due to exteroceptive factors beyond the pharmacological effects of alcohol potentiating smoking urge.

Knott V; Cosgrove M; Villeneuve C; Fisher D; Millar A; McIntosh J. EEG correlates of imagery-induced cigarette craving in male and female smokers. Addictive Behaviors 33(4): 616-621, 2008. (11 refs.)

Functional neuroimaging studies of cue-elicited craving in smokers have identified a distributed system of brain activation which includes the frontal cortex. As electroencephalographic (EEG) activity recorded from frontal brain regions indexes emotive functions, which are believed to play a key role in craving processes, this study examined frontal EEG in 20 cigarette smokers (10 male) exposed to imagery scripts containing positive, negative, or neutral affective content with and without descriptions of smoking urges. Urge scripts increased subjective cravings related to both the rewarding and withdrawal-relief properties of smoking, the latter tending to be greater in female smokers, as were self-reports of frustration. The emotional content of scripts did not moderate urges or EEG but urge scripts were found to: a) decrease activity of delta in male smokers and to increase activity of beta, a pattern which has also been seen with acute smoking, and b) increase activity of theta, a response which has also been seen with smoking abstinence. This imagery-elicited neuroelectric profile, appearing to reflect opposing actions of reward and withdrawal, suggests that EEG may be a sensitive tool for probing the multidimensional nature of craving.

Koob GF. Neurobiological substrates for the dark side of compulsivity in addiction. (review). Neuropharmacology 56(Supplement 1): 18-31, 2009. (143 refs.)

Drug addiction can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Drug addiction impacts multiple motivational mechanisms and can be conceptualized'as a disorder that progresses from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, increases in anxiety-like responses, and increases in extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of addiction. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least in part, the compulsivity of addiction.

LaLumiere RT; Kalivas PW. Glutamate release in the nucleus accumbens core is necessary for heroin seeking. Journal of Neuroscience 28(12): 3170-3177, 2008. (47 refs.)

Long-term changes in glutamate transmission in the nucleus accumbens core (NAcore) contribute to the reinstatement of drug seeking after extinction of cocaine self-administration. Whether similar adaptations in glutamate transmission occur during heroin and cue-induced reinstatement of heroin seeking is unknown. After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training, heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions. Microdialysis was conducted in the NAcore during reinstatement of heroin seeking in animals extinguished from heroin self-administration or in subjects receiving parallel (yoked) noncontingent saline or heroin. Reinstatement by either heroin or cue increased extracellular glutamate in the NAcore in the self-administration group, but no increase was elicited during heroin-induced reinstatement in the yoked control groups. The increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NAcore with tetrodotoxin or by inhibiting glutamatergic afferents to the NAcore from the prelimbic cortex. Supporting critical involvement of glutamate release, heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NAcore. Interestingly, although a heroin-priming injection increased dopamine equally in animals trained to self-administer heroin and in yoked-saline subjects, inhibition of dopamine receptors in the NAcore also blocked heroin- and cue-induced drug seeking. Together, these findings show that recruitment of the glutamatergic projection from the prelimbic cortex to NAcore is necessary to initiate the reinstatement of heroin seeking.

Levy MS. Listening to our clients: The prevention of relapse. Journal of Psychoactive Drugs 40(2): 167-172, 2008. (13 refs.)

A survey to assess the most common reasons for relapse was developed and administered to 335 individuals who were current clients in various levels of care in a large substance abuse treatment program in order to better understand what factors were most relevant for relapse among these clients. Several reasons for relapse were chosen significantly more often than others. Common reasons for relapse for both men and women were. the following: feeling bored, feeling anxious or stressed, wanting to use and get high, believing that use could occur without getting readdicted, and relationship problems and break up. In addition, men also commonly reported anger, having too much money, and no longer attending meetings as significant reasons for relapse. Among female clients, depression, loneliness, and the pain of withdrawal were among their top reasons for relapse. As a result of this survey, specific groups were developed and implemented in an effort to better address the unique reasons for relapse that our clients most commonly reported. It is hoped that the addition of these groups will help to improve overall treatment outcome of the clients who are served by the agency.

Martinotti G; Andreoli S; Di Nicola M; Di Giannantonio M; Sarchiapone M; Janiri L. Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics. Human Psychopharmacology. Clinical and Experimental 23(5): 417-424, 2008. (44 refs.)

Aims: Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability. Methods: Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale. Results: Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia. Discussion In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse.

Martinotti G; Cloninger CR; Janiri L. Temperament and character inventory dimensions and anhedonia in detoxified substance-dependent subjects. American Journal of Drug and Alcohol Abuse 34(2): 177-183, 2008. (20 refs.)

In this study we aimed to investigate the relationship between anhedonia, craving and temperament and character dimensions in a sample of 50 patients with alcohol and opiate dependence recruited after a period of detoxification. The following scales were applied: Snaith-Hamilton Pleasure Scale (SHAPS), Bech-Rafaelsen Melancholia Scale (BRMS), Scale for the Assessment of Negative Symptoms (SANS), Visual Analogue Scales (VAS) for craving, and Temperament and Character Inventory (TCI). The temperament dimension of Novelty Seeking was positively correlated to craving and anhedonia (p<.01), with a higher score of Novelty Seeking in the subsample of anhedonic subjects with respect to both non-anhedonic and control subjects. In our study, the possibility that difficulty in experiencing pleasure in psychiatric disorders can lead to the use of psychoactive substances in an attempt to decrease anhedonia, is extended to subjects without psychiatric disorders who may try substances to counterbalance a tonic state of anhedonia.

Matto HC; Strolin JS; Mogro-Wilson C. A pilot study of a dual processing substance user treatment intervention with adults. Substance Use & Misuse 43(3/4): 285-294, 2008. (24 refs.)

This study responds to the identified need for evidence-based substance abuse interventions by examining the effects of an innovative dual processing substance use intervention aimed at decreasing the risk for substance relapse by targeting emotional regulation capacity. The study was completed in partnership with a Latino-serving community-based substance user treatment agency in a rural Northeastern region of the United States in 2005-2006 and was supported with pilot monies from the University at Albany School of Social Welfare NIDA-funded research center. The sample (N = 29) was comprised of adults with a diagnosis of substance dependence seeking treatment in an outpatient program. Study findings indicated that individuals who participated in the dual-processing treatment group decreased their craving with a trend toward increased self-efficacy over time in treatment and did not show treatment response differences across Latino and non-Latino clients, suggesting that treatment application was similar across these groups. The study's limitations are noted.

McClernon FJ; Kozink RV; Rose JE. Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues. Neuropsychopharmacology 33(9): 2148-2157, 2008. (50 refs.)

Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerstrom test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.

McRobbie H; Hajek P; Locker J. Does the reaction of abstaining smokers to the smell of other people's cigarettes predict relapse? Addiction 103(11): 1883-1887, 2008. (17 refs.)

Aims: Recent ex-smokers report a range of reactions to other people's cigarette smoke. We examined the hypothesis that those who find the smell of smoke pleasant and tempting are more likely to relapse than those who have a neutral or even negative reaction to it. Design A total of 1110 consecutive patients who attended for smoking cessation treatment and achieved at least 1 week of validated abstinence provided weekly ratings of their reactions to other people's cigarette smoke together with routine baseline measures and weekly ratings of withdrawal discomfort [measured on the Mood and Physical Symptom Scale (MPPS)]. Findings Twenty-three per cent of the sample found the smell of other people's cigarette smoke during their first week of abstinence pleasant, and 54% found it tempting. There was only a modest correlation between the two variables. Finding the smoke pleasant was not related to smoking status in the following week, but finding the smoke tempting predicted relapse. Ratings of temptation were related to the severity of withdrawal discomfort and to dependence. Entering MPPS ratings of urges to smoke in the given week into regression analysis resulted in the general urges to smoke, rather than urges elicited by other people's smoke, becoming a significant predictor of smoking status in the following week. In patients who maintained continuous abstinence throughout 4 weeks of treatment the pleasantness ratings remained stable, while the ratings of temptation steadily decreased. Conclusions: In abstaining smokers, the like or dislike of other people's smoke is not related to relapse. The temptation to smoke elicited by other people's smoke is related to outcome, but only as an indicator of a general 'temptation threshold'. Patients who find other people's smoke tempting can be reassured that this reaction will gradually decrease.

Mehringer AM; Pomerleau CS; Snedecor SA; Finkenauer R. Favorite cigarette of the day in a random sample of women smokers. Addictive Behaviors 33(6): 848-852, 2008. (9 refs.)

From a random digit dialing survey of American women, we assessed current smokers (n=371). Respondents were 33.6 +/- 7.6 years old, 49.6% married, and 87.6% White, with an FTND score of 3.9 +/- 2.6. When asked "which cigarette of the day would be the most difficult for you to give up?" 30 women gave uncodable responses and 341 women provided answers subsequently coded into 5 categories: FIRST; 43.7%, MEAL; 29.3%, LAST; 13.8%, ROUTINE; 7.3%, and ENHANCE; 5.9%. Response groups differed significantly on age (p<.01), smoking rate (p <.001), time to first cigarette (p <.001), and self-rated health (p <.05). In post hoc analyses, FIRST were older, smoked more cigarettes/day, and smoked sooner after waking than at least one other group. LAST smoked the fewest cigarettes/day, and ENHANCE rated their health significantly better than did all other groups. The FTND is coded as 1 for "first" and 0 for any other response. Examining more closely the richness contained in that "other" category is a novel approach that may prove useful as a phenotyping tool.

Mendelson JH; Goletiani N; Sholar MB; Siegel AJ; Mello NK. Effects of smoking successive low- and high-nicotine cigarettes on hypothalamic-pituitary-adrenal axis hormones and mood in men. (review). Neuropsychopharmacology 33(4): 749-760, 2008. (101 refs.)

Smoking one cigarette produces rapid nicotine dose-related increases in hypothalamic-pituitary-adrenal (HPA) axis hormones, mood, and heart rate, but relatively little is known about the effects of smoking several cigarettes successively. Twenty-four healthy adult men who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for nicotine dependence provided informed consent. After overnight abstinence from smoking, men smoked three low- or high-nicotine cigarettes for 4 min each at 60 min intervals. Samples for nicotine and hormone analysis, Visual Analog Scale (VAS) ratings of subjective effects and heart rate were collected at 4, 8, 12, 16, 20, 30, 40, and 50 min after each cigarette. After low- nicotine cigarettes, nicotine levels, adrenocorticotropin hormone, and heart rate did not increase significantly, cortisol and dehydroepiandrosterone decreased significantly, and positive VAS ratings were lower but parallel to ratings after high-nicotine cigarette smoking. After high-nicotine cigarettes, peak nicotine levels increased monotonically. HPA axis hormones increased after smoking, but peak levels did not differ significantly after successive high-nicotine cigarettes. Positive VAS ratings and heart rate increased after each high-nicotine cigarette, but peak levels were lower after smoking the second and third cigarette. 'Craving' decreased significantly after smoking both low- and high-nicotine cigarettes, then gradually increased during the 60 min interval between cigarettes. These data are consistent with clinical reports that the first cigarette after overnight nicotine abstinence is most salient. Tolerance to the subjective and cardiovascular effects of nicotine developed rapidly during repeated cigarette smoking, but nicotine-stimulated increases in HPA axis hormones did not change significantly.

Miranda R; Rohsenow DJ; Monti PM; Tidey J; Ray L. Effects of repeated days of smoking cue exposure on urge to smoke and physiological reactivity. Addictive Behaviors 33(2): 347-353, 2008. (10 refs.)

The present study investigated the effects of repeated days of laboratory-based smoking cue exposure on subjective and physiologic cue reactivity. Twenty non-treatment seeking moderate/heavy smokers completed three laboratory sessions approximately 7 days apart, each following a 10-hour nicotine deprivation period. Cue reactivity procedures consisted of a relaxation trial followed by two trials of in vivo cue exposure. Dependent measures included urge to smoke, a withdrawal questionnaire, mean arterial pressure (MAP), and heart rate (HR). A Condition (relaxation vs. cue exposure) by Day (1, 2, or 3) analysis of variance revealed a significant main effect of Condition (greater urge to smoke after cue exposure) but no significant main or interaction effect for Day. Similarly, MAP and HR change scores following cue exposure did not differ across test days. Cue-elicited changes in withdrawal symptoms were only observed on Day 1, but not when the interday interval was covaried. Results suggest that laboratory-based cue-elicited changes in urge to smoke, MAP, and HR are stable over three separate days.

Munafo MR; Johnstone EC. Smoking status moderates the association of the dopamine D4 receptor (DRD4) gene VNTR polymorphism with selective processing of smoking-related cues. Addiction Biology 13(3/4): 435-439, 2008. (25 refs.)

Recently, a variable number of tandem repeats (VNTR) polymorphism in the dopamine D4 receptor (DRD4) gene has been reported to be associated with greater craving and more attention to smoking cues, following a cue-elicited craving procedure. We investigated whether the DRD4 VNTR 7-repeat polymorphism is associated with selective processing of smoking-related stimuli, using a modified Stroop task, and whether smoking status moderates this association. Thirty-one current smokers and 17 ex-smokers attended a single testing session and completed the modified Stroop task. The experimental design included two between-subjects factors of smoking status (current smoker, ex-smoker) and DRD4 genotype (short, long). The DRD4 VNTR polymorphism was associated with selective processing of smoking-related stimuli in ex-smokers but not in current smokers. Our data, therefore, provide partial support for our primary hypothesis and extend on previous work which suggests a role for variation at the DRD4 locus in modulating reactivity to drug-related cues.

Nakama H; Chang L; Cloak C; Jiang C; Alicata D; Haning W. Association between psychiatric symptoms and craving in methamphetamine users. American Journal on Addictions 17(5): 441-446, 2008. (24 refs.)

This study examined the differences in psychiatric symptoms between adult methamphetamine users (n = 46) and control subjects (n = 31), the relationship between psychiatric symptoms and the intensity of methamphetamine craving, and whether psychiatric symptoms were correlated to methamphetamine drug-usage variables (ie, length of abstinence, frequency, duration, and lifetime grams). We found that depressive symptoms on the Center for Epidemiology Studies-Depression (CES-D) and many other psychiatric symptoms on the Symptom Checklist-90 (SCL-90) significantly correlated with craving methamphetamine on the visual analog scale (VAS) for craving. Methamphetamine users had significantly more depressive symptoms (on CES-D) and psychotic symptoms (on SCL-90) compared to controls. There were no significant correlations between psychiatric symptoms and methamphetamine-usage variables. This study provides the first evidence to suggest that depressive symptoms (on CES-D) and psychiatric symptoms (on SCL-90) are strongly associated with the intensity of craving (on VAS) for the drug in methamphetamine users. However, the methamphetamine usage variables had no relationship with psychiatric symptoms. Therefore, methamphetamine users, regardless of their usage patterns, may benefit from treatment of their psychiatric symptoms in order to minimize craving and subsequent relapse to drug use.

Nejtek VA; Avila M; Chen LA; Zielinski T; Djokovic M; Podawiltz A et al. Do atypical antipsychotics effectively treat co-occurring bipolar disorder and stimulant dependence? A randomized, double-blind trial. Journal of Clinical Psychiatry 69(8): 1257-1266, 2008. (41 refs.)

Objectives: The primary objective was to compare the efficacy and tolerability of quetiapine and risperidone in the treatment of mood symptoms, drug cravings, and drug use in outpatients with concurrent DSM-IV-defined bipolar I or If disorder and cocaine or methamphetamine dependence. Method: Men and women of all ethnic origins, 20 to 50 years of age, were eligible to participate. Persons were excluded if they were inpatients, met DSM-IV criteria for substance-induced mood disorder, had any other substance dependence, were euthymic or suicidal, had any life-threatening illnesses, or were currently receiving antipsychotic medications. Duration of the trial was 20 weeks. Study participants attended weekly visits and were evaluated for mood symptoms, drug cravings, drug use, and medication side effects. Treatment outcomes were analyzed using linear mixed models. Fixed-effects terms for medication group, study week, and group-by-study-week were included in the models. The study was conducted between October 2002 and November 2006. Results: Of 124 consenting outpatients, an evaluable sample of 80 patients who attended baseline and at least I follow-up study visit was formed. The mean +/- SD exit dose for quetiapine was 303.6 +/- 151.9 mg/day and 3.1 +/- 1.2 mg/day for risperidone. Both quetiapine (N = 42) and risperidone (N = 38) significantly improved manic and depressive symptoms and reduced drug cravings (p < .0005) compared to baseline. Decreased drug cravings were related to less frequent drug use p = .03). The 2 medications did not significantly differ in their effects on mood symptoms, drug craving, or drug use. Conclusions: Relative to baseline mood and drug-craving status, both quetiapine and risperidone were associated with manic, mixed, and depressive symptom improvement and reduced drug cravings. Both medications were well tolerated. The interpretation of these results is limited by the absence of a placebo control. Trial Registration: clinicaltrials.gov Identifier: NCT00227123.

Nidecker M; DiClemente CC; Bennett ME; Bellack AS. Application of the Transtheoretical Model of change: Psychometric properties of leading measures in patients with co-occurring drug abuse and severe mental illness. Addictive Behaviors 33(8): 1021-1030, 2008. (53 refs.)

People with severe mental illness (SMI) have high rates of substance use disorders. The Transtheoretical Model (TTM) is a framework for understanding behavior change. There are five leading measures associated with the TTM - University of Rhode Island Change Assessment, Processes of Change Scale, Decisional Balance Scale, Abstinence Self-Efficacy Scale, and Temptation to Use Drugs Scale. While these measures have been found to be reliable and valid in primary substance abusers, it is unknown if these measures are relevant in people with co-occurring SMI and substance use disorders (SUD). We evaluated the psychometric properties of these measures in a sample (n = 240) of people with co-occurring disorders. Participants met DSM-IV criteria for schizophrenia/schizoaffective disorder or non-psychotic affective disorder, and current cocaine dependence or cocaine dependence in remission. All subscales showed good reliability and validity in the total sample. Analyses within diagnostic groups showed good reliability and validity in most groups, with some falling off in the affective disorders and remitted cocaine dependence groups. Overall, findings support the use of these measures in people with co-occurring disorders.

O'Connell KA; Schwartz JE; Shiffman S. Do resisted temptations during smoking cessation deplete or augment self-control resources? Psychology of Addictive Behaviors 22(4): 486-495, 2008. (55 refs.)

A resource depletion model of self-control posits that for some period following performance of a task requiring self-control, self-control will be reduced and thus less available for use in a subsequent task. Using 2 substantial data sets collected in real time from individuals who were trying to quit smoking (1,660 and 9,516 temptation episodes collected from 61 and 248 individuals, respectively), we evaluated this model by testing the hypotheses that the number and length of resisted temptations and the intensity of the most recently reported urge during the prior 4 hr predict decreased self-control and increased likelihood of lapsing. Survival and multilevel regression modeling showed that contrary to the hypothesis, the number of recently resisted temptations predicted a lower risk of lapsing in both samples. Duration of resisted temptations had no significant effect in either sample. Intensity of most recently reported urge predicted lapsing in I data set but not in the other. Overall, there was little support for the resource depletion model. The protective effect of successfully resisting temptations was an unexpected but provocative finding.

Oshri A; Tubman JG; Wagner EF; Leon-Morris S; Snyders J. Psychiatric symptom patterns, proximal risk factors, and sexual risk behaviors among youth in outpatient substance abuse treatment. American Journal of Orthopsychiatry 78(4): 430-441, 2008. (91 refs.)

The purpose of the current study was to classify adolescents receiving outpatient treatment for alcohol or other drug, (AOD) problems via self-reports of the Diagnostic and Statistical Manual of Mental Disorders (4th ed. American Psychiatric Association. 1994) psychiatric symptoms, and to identify group differences in measures of proximal risk factors for sexual risk behaviors (SRBs) and self-reported SRBs. Structured interviews were administered to 300 adolescent clients (202 mates. 98 females M = 16.22 years: SD = 1.13) receiving, treatment services as part of a larger National Institute on Alcohol Abuse and Alcoholism (NIAAA)-funded randomized clinical trial. Ward's method cluster analysis (Ward, 1963) was used to classify adolescents into distinct groups based on psychiatric symptom profiles. A multivariate analysis of variance was used to identify significant between-cluster differences in self-reported SRBs and Proximal risk factors for SRB. Substantial heterogeneity in patterns of psychiatric symptoms was documented in this treatment sample. Membership in certain psychiatric symptom clusters was associated with several self-reported SRBs and correlated proximal risk factors. Among youth receiving AOD treatment, interventions to promote HIV/STI risk reduction may need adaptation for those with differing psychiatric profiles.

Parker A; Gilbert D. Brain activity during anticipation of smoking-related and emotionally positive pictures in smokers and nonsmokers: A new measure of cue reactivity. Nicotine & Tobacco Research 10(11): 1627-1631, 2008. (21 refs.)

Previous studies have shown that a brain wave pattern known as stimulus preceding negativity (SPN) can index the anticipation of motivationally relevant events. The present study was the first to use SPN as an index of the motivational significance of smoking-related pictures. Emotionally positive and neutral pictures served as controls. The paradigm involved the following sequence: (a) presentation of a picture (S1) for 500ms, (b) a fixation cross for 3,500ms, (c) a second presentation (S2) of the same picture for 2,000ms, and (d) another fixation cross signifying the beginning of a new S1-S2 trial using a different picture. The participants (N=24, half smokers and half nonsmokers) viewed pictures from three categories (smoking-related, emotionally positive, or emotionally neutral). Consistent with predictions, smokers exhibited significantly greater mean SPN amplitudes in anticipation of smoking-related pictures relative to neutral pictures. Among nonsmokers the SPN was significantly smaller in anticipation of smoking pictures compared with neutral pictures. These findings are consistent with the incentive sensitization theory of addiction and other conditioning and cue-reactivity models.

Piasecki TM; McCarthy DE; Fiore MC; Baker TB. Alcohol consumption, smoking urge, and the reinforcing effects of cigarettes: An ecological study. Psychology of Addictive Behaviors 22(2): 230-239, 2008. (56 refs.)

Smokers (N = 74) who volunteered for a smoking cessation study monitored their daily experiences for up to 6 weeks prior to the quit date. Self-reports from 7,707 diary records were used to examine the associations among alcohol consumption (present in 607 diary records), situational factors, smoking, urge to smoke, and subjective consequences of smoking. Alcohol use, smoking urge, and the subjective effects of smoking were context dependent. Momentary reports of smoking and alcohol consumption were associated with one another. Alcohol use predicted smoking even when contextual factors were covaried. Alcohol use was associated with more frequent reports of urge to smoke. Alcohol was also associated with more frequent reports that the last cigarette produced a rush/buzz, was good tasting, and reduced the urge. However, effects for rush/buzz and urge reduction were qualified by interactions between alcohol use and the latency since smoking. Rush/buzz tended to be associated with alcohol use, regardless of smoking recency. Alcohol was associated with urge reduction only when the cigarette being appraised was smoked more than 15 minutes prior to the diary entry.

Piper ME; Federman EB; McCarthy DE; Bolt DM; Smith SS; Fiore MC et al. Using mediational models to explore the nature of tobacco motivation and tobacco treatment effects. Journal of Abnormal Psychology 117(1): 94-105, 2008. (70 refs.)

Various theories have proposed mechanisms for drug motivation and relapse. For instance, negative reinforcement theories focus on the alleviation of withdrawal. However, other theories and some data cast doubt on the importance of withdrawal as a motivator of addictive drug use. Using data from a randomized double-blind placebo-controlled smoking cessation treatment study (N = 608), this research examined the impact of withdrawal on drug motivation and the ability to maintain abstinence. Withdrawal was experimentally manipulated by randomly assigning participants to receive active bupropion versus placebo. Mediation analyses revealed that active bupropion reduced the amount of withdrawal and craving that individuals reported in the 1st week post quit; modest support was also found for smaller declines in positive affect. These effects, in turn, were all positively associated with posttreatment abstinence. These results implicate withdrawal as an important factor in motivating persistent tobacco use.

Reis AD; Castro LA; Faria R; Laranjeira R. Craving decrease with topiramate in outpatient treatment for cocaine dependence: an open label trial. Revista Brasileira de Psiguiatria 30(2): 132-135, 2008. (14 refs.)

Objective: To evaluate anticraving action and tolerability of topiramate in cocaine user treatment. Method: Male users of inhaled cocaine which met criteria for cocaine dependence (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) were selected for outpatient 12-week, open label trial with topiramate; individual dosage ranged between 25-300 mg/day. Main clinical variables were abstinence rate, craving intensity, frequency and duration, adherence, dropouts, side effects and impulsivity measure through Barratt Impulsivity Scale. Patients received assertive strategic counseling for abstinence assistance and medication monitoring evaluation every two weeks. Comparative analysis was made with intention to treat, missing values were replaced (last observation carried forward), and significance level was 5%. Results: Adherence to treatment was 57% (at least three evaluations), 32% dropped out (one evaluation). There were no severe side effects. Negative test average was 25.4% (31.2). Significant reduction in craving intensity and duration was observed in 25% of the sample. No statistical significant reduction in craving frequency was observed in 7.1%. Increase in frequency was observed in 10.7% and 82.1% did not present any variation. No significant statistical variations in Barratt Impulsivity Scale or in the total score were found in the final evaluation when compared to baseline. Conclusion: More randomized placebo-controlled trials with topiramate for cocaine dependants should be performed to evaluate preliminary evidence.

Sayette MA; Loewenstein G; Griffin KM; Black JJ. Exploring the cold-to-hot empathy gap in smokers. Psychological Science 19(9): 926-932, 2008. (38 refs.)

Many decisions related to cigarette smoking require people in an affectively neutral, or "cold," state to predict how they will feel or behave when in a craving, or "hot," state. Research in other domains has revealed that individuals in cold states often underestimate the impact of being in a hot state on their own future behavior. In a study testing whether this is true of cigarette craving, 98 smokers were assigned to one of three conditions: hot (during a high-craving first session, they made predictions about a high-craving state in a second session), cold (during a low-craving first session, they made predictions about a high-craving state in a second session), and comparison (they experienced a high-craving session only). As predicted, in contrast to smokers in the hot group, smokers in the cold group underpredicted the value they would place on smoking during the second session. Results support the existence of a cold-to-hot empathy gap in smokers and help to explain diverse aspects of tobacco addiction.

Schneider NG; Cortner C; Gould JL; Koury MA; Olmstead RE. Comparison of craving and withdrawal among four combination nicotine treatments. Human Psychopharmacology: Clinical and Experimental 23(6): 513-517, 2008. (19 refs.)

Objective: To assess the appearance of craving and withdrawal among four combination nicotine replacement treatments (NRTs). Methods: In a crossover trial of NRT preferences, 27 smokers tested 4 combinations of nicotine treatments: 2 mg/4 mg gums + 15 mg patch, 2 mg/4 mg lozenges + 15 mg patch, inhalers + 15 mg patch, and 10 + 15 mg double patch (similar to 25 mg). Overnight abstinence was required prior to 1/2 day testing of each combination. Combination NRTs were used for similar to 6 h/day. Subjects resumed smoking each afternoon. For this report, we used the Smoker Anchored Withdrawal Grid to look at craving and withdrawal scores over 5 days of testing (smoking baseline + four treatment days). Results: "Urge to smoke" and "total withdrawal" showed a rise from baseline to NRIF use for the double patch but not for the three acute + patch conditions. Lozenge/patch scores did not rise from baseline for "craving" and "miss a cigarette" but did for gum/patch, inhaler/patch. and double patch. The best relief occurred for NRTs of choice. Conclusion This was a small but suggestive finding regarding the potential of patch plus adjunct ad lib NRT. With little data on relief with NRT combinations, more systematic tests are needed.

Shiffman S. Effect of nicotine lozenges on affective smoking withdrawal symptoms: Secondary analysis of a randomized, double-blind, placebo-controlled clinical trial. Clinical Therapeutics 30(8): 1461-1475, 2008. (57 refs.)

Background: The suggested mechanism for the effects of nicotine replacement medications such as nicotine lozenges on smoking abstinence is reduction in the withdrawal symptoms of emotional distress and craving (the subjective desire to smoke). Objectives: This study assessed the effect of nicotine lozenges on affective withdrawal symptoms (collectively termed emotional distress) and craving over 6 weeks of treatment and the role of emotional distress and craving in mediating the effect of the lozenges on smoking abstinence. Methods: This was a secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of nicotine lozenges. High-dependence smokers (those who smoked their first cigarette of the day within 30 minutes of waking) were assigned to recieve the 4-mg lozenge; low-dependence smokers (those who smoked their first cigarette of the day > 30 minutes after waking) were assigned to receive the 2-mg lozenge. Participants were randomized to receive active or placebo lozenges within these dose and dependence strata. Smokers were to rate their withdrawal symptoms daily during the baseline week (while still smoking) and for 6 weeks after starting treatment. Study analyses included the effect of the active lozenge on affective symptoms (le, anxiety; anger, irritability, or frustration; difficulty concentrating; restlessness; and depressed mood) during weeks 1 through 6 in high- and low-dependence smokers; the prospective associations between these symptoms and craving and subsequent abstinence; and the mediating influence of these symptoms on the lozenge's effect on abstinence. The analyses included smokers who provided symptom data for the baseline period and for at least week after the initiation of treatment. Results: Of 1818 smokers enrolled in the original study, this analysis included data from 1144. The population was predominantly white, had a mean age ranging from 40.65 to 46.01 years, and included slightly more women than men. The 2-mg lozenge did not have consistently significant effects on the withdrawal symptoms of emotional distress among low-dependence smokers; however, in high-dependence smokers, the 4-mg dose was associated with significant reductions versus placebo in overall emotional distress symptoms through week 4 (P < 0.001-P = 0.025), all individual symptoms through week 3 (P < 0.001-P = 0.035), and irritability and anxiety through week 4 (P = 0.002-P 0.049). In the low-dependence group, the 2-mg lozenge was associated with significant reductions versus placebo in craving through week 3 (P = 0.012-P = 0.033), whereas in the high-dependence group, the 4-mg lozenge was associated with significant reductions in craving in each of the first 6 weeks (P < 0.001-P = 0.028). Among high-dependence smokers, both week-1 and week-2 emotional distress scores were associated with a return to smoking by week 6 (P < 0.001); among low-dependence smokers, the association applied only to week-2 symptoms (P = 0.017). Week-1 and week-2 craving was associated with a return to smoking at week 6 in both groups (P < 0.001-P = 0.001). Emotional distress modestly and inconsistently mediated the effects of the lozenges, accounting for 3% to 13% of the treatment effects, whereas craving more strongly (though incompletely) mediated the treatment effects, particularly among high-dependence smokers, in whom it accounted for 29% to 39% of the treatment effects. Conclusions: In high-dependence smokers, the 4-mg nicotine lozenge significantly reduced all affective withdrawal symptoms through the first 4 weeks of treatment. Lozenge-related decreases in craving partially mediated the effect of treatment on abstinence, particularly in high-dependence smokers.

Shiffman S; Ferguson SG. The effect of a nicotine patch on cigarette craving over the course of the day: Results from two randomized clinical trials. Current Medical Research and Opinion 24(10): 2795-2804, 2008. (31 refs.)

Objectives: The objective of this analysis was to assess the efficacy of a 21 mg/24-h nicotine patch for the reduction of craving throughout the waking day, compared both to placebo, and to a 15 mg/16-h patch differing pharmacokinetic profile over the day. The primary end-point was craving during the evening hours, because previous research suggested that smoking relapse was particularly likely at that time. Research design and methods: Data were drawn from two similar randomized clinical trials among nicotine-dependent smokers who were quitting smoking: Study 1 compared the 21 mg/24-h patch to a placebo patch, while Study 2 compared the 21 mg/24-h patch to a 15 mg/16-h nicotine patch. In both studies, subjects (Study 1: n = 102; Study 2: n = 244) were prompted by an electronic diary to rate their craving multiple times per day during a 1 week baseline period, and for up to 2 weeks after quitting. For analysis, the day was divided into five blocks: morning (up to 10:59 a.m.), mid-day (11:00 a.m.-1:59 p.m.), afternoon (2:00 p.m.-4:59 p. m.), evening (5:00 p.m.-8:59 p.m.), and late night (9:00 p.m. onwards). The individual craving ratings were divided into three intervals based on time since quitting: Days 1-3, 4-7, and 8-14. Results: The 21 mg/24-h nicotine patch resulted in significantly lower craving during all post-quit intervals, at each time of day, both compared to placebo (Study 1), and compared to the 15 mg/16-h nicotine patch (Study 2). Study 2 saw a significant treatment by interval interaction: in later time intervals, the difference in craving experience between 24- and 16-h patch conditions shrunk - while remaining significantly different - as overall levels of craving experienced by subjects in the two groups dropped. Adverse events reported in both studies tended to be mild and transient, consistent with the well characterized adverse event profile of nicotine patches. Conclusions: Study 1 demonstrated that a 21 mg/24-h patch was effective in reducing craving throughout the day, including the evening period when relapse risk is heightened. A further study comparing the 21 mg/24-h patch to a 15 mg/16-h nicotine patch found that craving was significantly lower at all times of day for smokers using the 21 mg/24-h patch. The studies were limited in that craving was only monitored for the first 2 weeks of quitting (when craving is most prominent), and cannot elucidate the impact of patch use on craving outside of this time. Also, there was substantial attrition of the sample over time, partly due to relapse in all conditions.

Shippenberg TS; LeFevour A; Chefer VI. Targeting endogenous mu- and delta-opioid receptor systems for the treatment of drug addiction. (review). CNS & Neurological Disorders: Drug Targets 7(5): 442-453, 2008. (195 refs.)

Drug addiction is a chronic, relapsing disorder that is characterized by a compulsion to take drug regardless of the adverse consequences that may ensue. Although the involvement of mesoaccumbal dopamine neurons in the initiation of drug abuse is well-established, neuroadaptations within the limbic cortical-striatopallidal circuit that occur as a consequence of repeated drug use are thought to lead to the behavioral dysregulation that characterizes addiction. Opioid receptors and their endogenous ligands are enriched in brain regions comprising this system and are, thus, strategically located to modulate neurotransmission therein. This article will review data suggesting an important role of mu-opioid receptor (MOPr) and delta opioid receptor (DOPr) systems in mediating the rewarding effects of several classes of abused drugs and that aberrant activity of these opioid systems may not only contribute to the behavioral dysregulation that characterizes addiction but to individual differences in addiction vulnerability.

Shoptaw S; Heinzerling KG; Rotheram-Fuller E; Steward T; Wang J; Swanson AN et al. Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence. Drug and Alcohol Dependence 96(3): 222-232, 2008. (72 refs.)

Objective: To compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA-cravings. A secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. Methods: Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N=36) or placebo (twice daily; N=37) for 12-weeks under double-blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions. Results: There were no statistically significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA-cravings, or on study retention. In a post hoc analysis, there was a statistically significant effect of bupropion treatment on MA use among participants with lighter (0-2 MA-positive urines), but not heavier (3-6 MA-positive urines) MA use during baseline (OR = 2.81, 95% CI = 1.61-4.93, p < 0.001 for MA-free week with bupropion among light users). Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost five cigarettes per day (p = 0.0002). Conclusion: Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light-MA users is warranted.

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

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

Smith AE; Cavallo DA; Dahl T; Wu R; George TP; Krishnan-Sarin S. Effects of acute tobacco abstinence in adolescent smokers compared with nonsmokers. Journal of Adolescent Health 43(1): 46-54, 2008. (37 refs.)

Purpose: Abstinence effects such as nicotine withdrawal and mood changes contribute to the maintenance of cigarette smoking in adult smokers, and emerging reports on adolescent smokers suggest they may experience similar subjective effects when deprived. This study aimed to prospectively document tobacco abstinence-induced changes during the first 48 hours of abstinence in adolescent smokers compared with nonsmokers, to distinguish effects distinct from typical adolescent lability. Methods: Fifty-seven adolescent smokers and 44 adolescent nonsmokers were assessed during a 48-hour inpatient session. Characteristic nicotine withdrawal symptoms, cravings for cigarettes, and mood symptoms were measured at 13 time points following initiation of abstinence. Results: The only abstinence-related effects observed were changes in craving for tobacco and feelings of anger. Tobacco craving increased and peaked quickly following initiation of abstinence and displayed a slight decrease toward the end of the 48-hour abstinence period, while anger symptoms peaked after a more prolonged abstinence. Overall, smokers' symptoms and cravings were positively associated with amount of daily smoking but not with reports of dependence or biological measures of extent of use. Conclusions: We observed that among adolescent smokers, the primary effects associated with abstinence from cigarettes are relatively minimal, and include a heightened and persistent craving to smoke and increases in anger. Although smokers had greater negative mood symptoms compared with nonsmokers, the presence and severity of most of these symptoms appear to be minimally altered by abstinence and not associated with dependency or biological indicators of amount of tobacco use.

Smith MA; Schmidt KT; Lordanou JC; Mustroph ML. Aerobic exercise decreases the positive-reinforcing effects of cocaine. Drug and Alcohol Dependence 98(1/2): 129-135, 2008. (71 refs.)

Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3�mg/kg/infusion) and high (1.0�mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

Thomas MJ; Kalivas PW; Shaham Y. Neuroplasticity in the mesolimbic dopamine system and cocaine addiction. (review). British Journal of Pharmacology 154(2): 327-342, 2008. (169 refs.)

The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking.

Thorndike AN; Regan S; McKool K; Pasternak RC; Swartz S; Torres-Finnerty N. Depressive symptoms and smoking cessation after hospitalization for cardiovascular disease. Archives of Internal Medicine 168(2): 186-191, 2008. (41 refs.)

Background: Although smoking cessation is essential for prevention of secondary cardiovascular disease (CVD), many smokers do not stop smoking after hospitalization. Mild depressive symptoms are common during hospitalization for CVD. We hypothesized that depressive symptoms measured during hospitalization for acute CVD would predict return to smoking after discharge from the hospital. Methods: This was a planned secondary analysis of data from a placebo-controlled, double-blind, randomized trial of bupropion hydrochloride therapy in 245 smokers hospitalized for acute CVD. All subjects received smoking counseling in the hospital and for 12 weeks after discharge. Depressive symptoms were measured during hospitalization with the Beck Depression Inventory (BDI), and smoking cessation was biochemically validated at 2-week, 12-week, and 1-year follow-up. The effect of depressive symptoms on smoking cessation was assessed using multiple logistic regression and survival analyses. Results: Twenty-two percent of smokers had moderate to severe depressive symptoms (BDI >= 16) during hospitalization. These smokers were more likely to resume smoking by 4 weeks after discharge (P=.007 incidence rate ratio, 2.40; 95% confidence interval, 1.48-3.78) than were smokers with lower BDI scores. Smokers with low BDI scores were more likely to remain abstinent than were those with high BDI scores at 3-month follow-up (37% vs 15%; adjusted odds ratio, 3.02; 95% confidence interval, 1.28-7.09) and 1-year follow-up (27% vs 10%; adjusted odds ratio, 3.77; 95% confidence interval, 1.31-10.82). We estimate that 27% of the effect of the BDI score on smoking cessation was mediated by nicotine withdrawal symptoms. Conclusions: Moderate to severe depressive symptoms during hospitalization for acute CVD are independently associated with rapid relapse to smoking after discharge and lower rates of smoking cessation at long-term follow-up. The relationship was mediated in part by the stronger nicotine withdrawal symptoms experienced by smokers with higher depressive symptoms.

Toll BA; Cooney JL; Mckee SA; O'Malley SS; Cooney NL. Correspondence of interactive voice response (IVR) reports of nicotine withdrawal, craving, and negative mood with questionnaire ratings. Nicotine & Tobacco Research 10(6): 1057-1064, 2008. (25 refs.)

This study focuses on comparing reports of nicotine withdrawal, craving, and depressive symptoms obtained using an Interactive Voice Response (IVR) system and several questionnaires. As part of a smoking cessation trial, daily reports of withdrawal, craving, and negative mood were collected using an IVR system for 7 days after participants attempted to quit smoking, and several pencil and paper questionnaires (i.e., the Minnesota Nicotine Withdrawal Scale, the Questionnaire on Smoking Urges, and the Center for Epidemiological Studies-Depression) were completed a week after the target quit date. The sample was composed of 378 daily smokers. Moderate to high correlations were found between the research questionnaires obtained at the end of the week and the corresponding daily IVR reports of nicotine withdrawal, craving, and depressive symptoms. However, the sample size decreased on each day of IVR reporting due to attrition. Thus, an appealing aspect of daily assessment using an IVR system is that it can provide additional data that are not obtained with paper and pencil assessments given once per week, but it will be important for future studies to concentrate on improving adherence with the IVR system in this population.

Traylor AC; Bordnick PS; Carter BL. Assessing craving in young adult smokers using virtual reality. American Journal on Addictions 17(5): 436-440, 2008. (18 refs.)

Cigarette smokers, when confronted with cues associated with smoking, evidence strong reactions, including increased craving. These reactions have not been extensively studied in young adult smokers, a group that research suggests may respond differently than adults or adolescent smokers. We used virtual reality, which presents a complex array of smoking cues that may be particularly salient to young adult smokers, and measured self-report of craving. Young adult smokers responded strongly to these cues and, unlike adults, did not return to a baseline of craving following cue exposure, suggesting young adult smokers differ from other smokers in terms of cue responses.

van der Meer Sanchez Z; Nappo SA. Religious treatments for drug addiction: An exploratory study in Brazil. Social Science & Medicine 67(4): 638-646, 2008. (38 refs.)

The main objective of the present work is to understand the processes used in emerging Catholic and Protestant religious interventions for recovery from drug dependence, from the vantage point of individuals subjected to them. A qualitative method and an intentional sample selected by criteria were adopted for this investigation, which was conducted in Sao Paulo, Brazil. An in-depth semi-structured interview was conducted with 57 predominantly male former drug users who fit the criteria: they had been submitted to non-medical religious treatments to treat dependence and were abstinent for at least 6 months. Crisis was found to be the main reason leading interviewees to seek treatment; this includes, losing family, losing employment, and experiencing severe humiliation. Evangelicals most used religious resources exclusively as treatment, showing strong aversion to the role of doctors and to any type of pharmacological treatment. A common feature of Catholic and Protestant groups is the importance ascribed to praying and talking to God, described by subjects as strongly anxiolytic, and a means to control drug craving. Confession and forgiveness, through faith conversion or penitences, respectively, appeal strongly to the restructuring of life and increase of self-esteem. Religious interventions were considered effective by the individuals who underwent them and were seen as attractive for the humane, respectful treatment they delivered. The key aspects of this type of treatment are social support provided by the receiving group, equal treatment, and instant, judgment-free acceptance. The success of these actions, then, is not only due to some "supernatural" aspect, as might be assumed, but also more to the unconditional dedication of human beings to their peers. Given the difficulty in treating drug dependence, religious interventions could be used as a complementary treatment for conventional therapies.

van Zundert RMP; Engels RCME; Kleinjan M; van den Eijnden RJJM. An integration of parents and best friends smoking, smoking-specific cognitions, and nicotine dependence in relation to readiness to quit smoking: A comparison between adolescents with and without asthma. Journal of Pediatric Psychology 33(8): 821-832, 2008. (52 refs.)

Objective: To study the impact of parents and best friends smoking, nicotine dependence, and craving on smoking-specific cognitions, and readiness to quit in adolescents with and without asthma. Methods: Structural equation analyses were applied to data from a sample of 1,120 daily smoking adolescents, 83 of whom had asthma. Results Adolescents with asthma felt more ready to quit, and cognitions were more strongly related to readiness to quit among adolescents with asthma than among adolescents without asthma. Moreover, best friends smoking seemed more relevant to the cognitions of adolescents with asthma. Nicotine dependence and craving were strongly related to cognitions, and to readiness to quit in both groups. The relation between craving and readiness to quit, however, was stronger among participants with asthma. Conclusions: Reduction of nicotine dependence and craving is essential for both groups. Youth with asthma may benefit even more from cognitive-based cessation services than healthy youth. The finding that adolescents with asthma are relatively more ready to quit, and that their cognitions are more easily affected can be turned into advantages in asthma-specific cessation services.

Verdejo-Garcia A; Bechara A. A somatic marker theory of addiction. (review). Neuropharmacology 56(Supplement 1): 48-62, 2009. (142 refs.)

Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. Growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioral studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of "craving", including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent to which these studies Support a somatic marker theory of addiction. We conclude that there are at least two underlying types of dysfunction where emotional signals (somatic markers) turn in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action.

Weinberger AH; Krishnan-Sarin S; Mazure CM; McKee SA. Relationship of perceived risks of smoking cessation to symptoms of withdrawal, craving, and depression during short-term smoking abstinence. Addictive Behaviors 33(7): 960-963, 2008. (7 refs.)

The current study examined the relationship between perceived risks of quitting smoking and the self-reported experience of risks (e.g., cravings) during short-term abstinence. Participants (n=55) were daily smokers enrolled in a study of contingency management for smoking cessation with biochemically confirmed abstinence for I week. Participants were divided into groups of higher and lower perceived risk of quitting. There were no differences by risk group in demographics or baseline smoking, nicotine dependence, cravings, withdrawal, and depression. Although participants with higher levels of perceived risks reported a similar pattern of cravings and withdrawal symptoms during abstinence, they experienced higher levels of cravings, withdrawal symptoms, and depression than participants with lower risk beliefs. There were no differences in the relationship of risk to withdrawal symptoms by gender. Smokers with higher levels of perceived risk may find it more difficult to quit and remain abstinent due to higher levels of anticipated or experienced withdrawal symptoms and may benefit from targeted behavioral interventions with regard to risk perception and enhanced coping with withdrawal and other effects of smoking cessation.

West O; Roderique-Davies G. Development and initial validation of a Caffeine Craving Questionnaire. Journal of Psychopharmacology 22(1): 80-91, 2008. (74 refs.)

Craving for caffeine has received little empirical attention, despite considerable research into the potential for caffeine dependence. The main aim of this study was to develop, and initially validate, a multi-item, multidimensional instrument to measure cravings for caffeine. Participants were 189 caffeine consumers who completed the Questionnaire of Caffeine Cravings, which was based on the Questionnaire of Smoking Urges (QSU), in one of five naturally occurring periods of abstinence; 1-15 min; 16-120 mins; 3-7 h; 12-48 h and +48 h. Exploratory factor analysis suggested a three-factor solution best described the data; Factor 1 reflected strong desires, intentions and positive reinforcement; Factor 2 reflected mild/general positive and negative reinforcement and Factor 3 reflected functional/mood-based negative reinforcement. Significantly higher Factor 1 and Factor 2 scores were recorded for high frequency users; significantly higher Factor 1 and Factor 3 scores were recorded as a function of increased levels of dependence. Duration of abstinence did not significantly effect cravings across all three factors. Regression analyses suggested level of dependence best predicted both current cravings and frequency of daily use. These findings suggest caffeine cravings may be conceptualized multidimensionally and further validates the use of multidimensional, multi-item instruments. Cravings for caffeine may manifest and be detected across varying levels of dependence and, frequency of use and independently of duration of abstinence.

Wolfling K; Flor H; Grusser SM. Psychophysiological responses to drug-associated stimuli in chronic heavy cannabis use. European Journal of Neuroscience 27(4): 976-983, 2008. (50 refs.)

Due to learning processes originally neutral stimuli become drug-associated and can activate an implicit drug memory, which leads to a conditioned arousing 'drug-seeking' state. This condition is accompanied by specific psychophysiological responses. The goal of the present study was the analysis of changes in cortical and peripheral reactivity to cannabis as well as alcohol-associated pictures compared with emotionally significant drug-unrelated and neutral pictures in long-term heavy cannabis users. Participants were 15 chronic heavy cannabis users and 15 healthy controls. Verbal reports as well as event-related potentials of the electroencephalogram and skin conductance responses were assessed in a cue-reactivity paradigm to determine the psychophysiological effects caused by drug-related visual stimulus material. The evaluation of self-reported craving and emotional processing showed that cannabis stimuli were perceived as more arousing and pleasant and elicited significantly more cannabis craving in cannabis users than in healthy controls. Cannabis users also demonstrated higher cannabis stimulus-induced arousal, as indicated by significantly increased skin conductance and a larger late positivity of the visual event-related brain potential. These findings support the assumption that drug-associated stimuli acquire increased incentive salience in addiction history and induce conditioned physiological patterns, which lead to craving and potentially to drug intake. The potency of visual drug-associated cues to capture attention and to activate drug-specific memory traces and accompanying physiological symptoms embedded in a cycle of abstinence and relapse - even in a 'so-called' soft drug - was assessed for the first time.

Xu JS; Azizian A; Monterosso J; Domier C; Brody A; London E et al. Gender effects on mood and cigarette craving during early abstinence and resumption of smoking. Nicotine & Tobacco Research 10(11): 1653-1661, 2008. (60 refs.)

Women are more likely than men to relapse after initiating abstinence from cigarette smoking. The reasons for this phenomenon are unclear but may relate to negative mood, cigarette craving, or other symptoms of nicotine withdrawal. We addressed this issue in a study of 26 female and 38 male smokers. The Profile of Mood States, Shiffman-Jarvik Withdrawal Scale, and Urge to Smoke Scale were administered twice in each of two test sessions on different days. One session began within 1 hr after smoking ad libitum and the other followed overnight abstinence (13 hr). On each test day, the two assessment blocks were separated by a 5-10-min break, during which each participant smoked one cigarette. In the first test block, both men and women reported higher scores after 13 hr abstinence than after 1 hr abstinence on the tension-anxiety and anger-hostility subscales of the Profile of Mood States, and for the craving and psychological symptoms of the Shiffman-Jarvik Withdrawal Scale. Scores of female subjects showed significantly larger differences between sessions on the tension-anxiety subscale and a trend toward significance (p=.050) on the anger-hostility subscale of Profile of Mood States than those of males. Moreover, on the tension-anxiety subscale, women also reported a greater reduction than men from smoking one cigarette after overnight abstinence. The findings indicate that overnight abstinence produces more negative mood symptoms and cigarette craving in female smokers than in males, and that resumption of smoking produces greater relief from these symptoms in female smokers. These differences may contribute to the greater likelihood of relapse when women try to quit smoking.

Yamamoto RT; Karlsgodt KH; Rott D; Lukas SE; Elman I. Effects of perceived cocaine availability on subjective and objective responses to the drug. Substance Abuse Treatment, Prevention, and Policy 2(e-article 30), 2007. (65 refs.)

Rationale: Several lines of evidence suggest that cocaine expectancy and craving are two related phenomena. The present study assessed this potential link by contrasting reactions to varying degrees of the drug's perceived availability. Method: Non-treatment seeking individuals with cocaine dependence were administered an intravenous bolus of cocaine (0.2 mg/kg) under 100% ('unblinded'; N = 33) and 33% ('blinded'; N = 12) probability conditions for the delivery of drug. Subjective ratings of craving, high, rush and low along with heart rate and blood pressure measurements were collected at baseline and every minute for 20 minutes following the infusions. Results: Compared to the 'blinded' subjects, their 'unblinded' counterparts had similar craving scores on a multidimensional assessment several hours before the infusion, but reported higher craving levels on a more proximal evaluation, immediately prior to the receipt of cocaine. Furthermore, the 'unblinded' subjects displayed a more rapid onset of high and rush cocaine responses along with significantly higher cocaine-induced heart rate elevations. Conclusion: These results support the hypothesis that cocaine expectancy modulates subjective and objective responses to the drug. Provided the important public health policy implications of heavy cocaine use, health policy makers and clinicians alike may favor cocaine craving assessments performed in the settings with access to the drug rather than in more neutral environments as a more meaningful marker of disease staging and assignment to the proper level of care.

Zijlstra F; Veltman DJ; Booij J; van den Brink W; Franken IHA. Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males. Drug and Alcohol Dependence 99(1-3): 183-192, 2009. (73 refs.)

Aim: Drug-related stimuli may induce craving in addicted patients, prompting drug-seeking behaviour. In addition, studies have shown addicted patients to he less sensitive to pleasant, but non-drug-related, stimuli; a condition generally referred to as anhedonia. The neural correlates of cue-induced craving and anhedonia in opioid-dependent patients are, however, not well understood. We studied brain activation patterns following Visual presentation of neutral, pleasant and heroin-related cues. Methods: Detoxified opioid-dependent males (n = 12)and healthy male control subjects (n = 17) Underwent functional magnetic resonance imaging (fMRI) while subjects viewed neutral, pleasant and heroin-related images. In addition, subjective cue-elicited craving (OCDUS and DDQ) and anhedonia (SHAPS) were measured. Results: Opioid-dependent subjects, but not control subjects, showed significant increases in activation in hippocampal region and subcortical limbic structures in response to heroin-related stimuli with a significant group x stimulus interaction effect for the subthalamic nucleus (STN). Control subjects, but not opioid-dependent subjects, showed significant increases in activation of anterior frontal areas and basal ganglia while viewing pleasant images with a significant group X Stimulus interaction effect for bilateral anterior prefrontal cortex. Regression analyses showed a positive association between cue-elicited craving and ventral tegmental area (VTA) activation in response to heroin-related stimuli ill heroin-dependent patients. In addition, a negative correlation was found between self-reported anhedonia and medial prefrontal regions in both groups. Conclusions: Our findings suggest that the VTA is prominently involved ill cue-induced opioid craving for heroin Stimuli, ill addition to mesolimbic and mesocortical pathways as identified in previous research. The present study also provides further evidence for the involvement of the STN in reward processing. Finally, our data support the presence of reduced brain activation in heroin-dependent patients ill response to pleasant (non-drug-related) stimuli.