Significant association of nicotine reinforcement and cue reactivity: a translational study in humans and rats.

Relapse is common amongst smokers attempting to quit and tobacco cue-induced craving is an important relapse mechanism. Preclinical studies commonly use cue-induced reinstatement of nicotine seeking to investigate relapse neurobiology. Previous research suggests dependence severity and nicotine intake history affect smoking resumption and cue-induced reinstatement of nicotine seeking. However, behavioural data may be interpreted in terms of nicotine reinforcement. This translational study investigated if individual differences in objectively assessed nicotine reinforcement strength were associated with cue-reactivity in both rats and human smokers, which to our knowledge has not been investigated before. Rats (n = 16) were trained to self-administer nicotine and were tested on a progressive ratio schedule of nicotine reinforcement, to assess reinforcer strength, and on a test of cue-induced reinstatement of nicotine seeking. Nicotine reinforcement strength was assessed in human smokers (n = 104) using a forced choice task (nicotine containing vs. denicotinised cigarettes) and self-reported cue-induced craving was assessed following exposure to smoking and neutral cues. Responding for nicotine under progressive ratio was strongly positively correlated with cue-induced reinstatement of nicotine seeking in rats. Nicotine choices in human smokers were significantly associated with cue-induced craving controlling for dependence severity, years of smoking, and urge to smoke following neutral cues. Findings suggest nicotine reinforcement strength is associated with both types of cue-induced behaviour, implying some translational commonality between cue-induced craving in human smokers and cue-induced reinstatement of nicotine seeking in rats. Findings are discussed in relation to clinical implications and whether these laboratory tasks assess drug 'wanting'.

Impact of CYP2A6 Activity on Nicotine Reinforcement and Cue-Reactivity in Daily Smokers.

INTRODUCTION: Variation in CYP2A6, the primary enzyme responsible for nicotine metabolism, is associated with nicotine dependence, cigarette consumption, and abstinence outcomes in smokers. The impact of CYP2A6 activity on nicotine reinforcement and tobacco cue-reactivity, mechanisms that may contribute to these previous associations, has not been fully evaluated. AIMS AND METHODS: CYP2A6 activity was indexed using 3 genetic approaches in 104 daily smokers completing forced-choice and cue-induced craving tasks assessing nicotine reinforcement and tobacco cue-reactivity, respectively. First, smokers were stratified by the presence or absence of reduced/loss-of-function CYP2A6 gene variants (normal vs. reduced metabolizers). As nicotine metabolite ratio (NMR) is a reliable biomarker of CYP2A6 activity, our second and third approaches used additional genetic variants identified in genome-wide association studies of NMR to create a weighted genetic risk score (wGRS) to stratify smokers (fast vs. slow metabolizers) and calculate a wGRS-derived NMR. RESULTS: Controlling for race and sex, normal metabolizers (vs. reduced) selected a greater proportion of puffs from nicotine-containing cigarettes (vs. denicotinized) on the forced-choice task (p = .031). In confirmatory analyses, wGRS-based stratification (fast vs. slow metabolizers) produced similar findings. Additionally, wGRS-derived NMR, which correlated with actual NMR assessed in a subset of participants (n = 55), was positively associated with the proportion of puffs from nicotine-containing cigarettes controlling for race and sex (p = .015). None of the CYP2A6 indices were associated with tobacco cue-reactivity in minimally deprived smokers. CONCLUSIONS: Findings suggest increased nicotine reinforcement is exhibited by smokers with high CYP2A6 activity, which may contribute to heavier smoking and poorer cessation outcomes previously reported in faster metabolizers. IMPLICATIONS: CYP2A6 activity is a key determinant of smoking behavior and outcomes. Therefore, these findings support the targeting of CYP2A6 activity, either therapeutically or as a clinically relevant biomarker in a precision medicine approach, for tobacco use disorder treatment.

Cigarette Smoking During Pregnancy: Do Complete Abstinence and Low Level Cigarette Smoking Have Similar Impact on Birth Weight?

OBJECTIVES: Despite awareness of negative health outcomes associated with smoking, pregnant smokers might reduce their tobacco consumption thinking that a low smoking rate reduces smoking-related negative birth outcomes. We aimed to assess in a clinical sample whether there is a smoking rate that would not impact on birth weight (BW). METHODS: Pregnant smokers ≥18 years, gestational age of 9-20 weeks of amenorrhea, motivated to quit smoking, smoking ≥5 cigarettes/day (cpd) and their newborns (381 singleton, live births) were included in this secondary analysis of a French smoking cessation trial. RESULTS: The mean BW when the mother quit smoking was 3417 g (95 % CI: 3098-3738 g); when smoking >0<5 cpd, 3081g (3003-3159 g); when smoking 5-9 cpd, 3043 g (2930-3157 g); and when smoking ≥10 cpd, 2831 g (2596-3157 g) (p = .006). The corresponding effect sizes ranged from medium to large (Cohen's d for BW: 0.54, 0.57 and 0.85) compared to BW when the mother quit. In the multivariable analysis, adjusted for all significant confounders, when the mother smoked on average >0<5 cpd, the loss in BW was 228 g; when smoking 5-9 cpd, 251 g; and when smoking ≥10 cpd, 262 g (all p ≤ .02) compared to newborns' BW of mothers who stopped smoking since quit date. CONCLUSIONS: Even low cigarette consumption during pregnancy is associated with BW loss. All efforts should be made to help pregnant smokers quit completely during their pregnancy. IMPLICATIONS: As an alternative to quitting smoking, pregnant smokers reduce their smoking rate thinking that this diminishes smoking-related negative health outcomes. No study has established whether low smoking rate (more than 0 but less than 5 cpd) during pregnancy impacts BW compared to abstinence from smoking. Among treatment-seeking pregnant smokers BW of newborns of mothers who smoked even less than 5 cpd was significantly lower than of those whose mothers quit; effect sizes of different consumption levels on BW ranged from moderate (>0<5 cpd) to large (≥10 cpd). Even low smoking rate is associated with reduced BW compared to complete maternal smoking abstinence.

Predictors of the Perception of Smoking Health Risks in Smokers With or Without Schizophrenia.

OBJECTIVE: This study sought to examine the predictors of health risk perception in smokers with or without schizophrenia. METHODS: The health risk subscale from the Smoking Consequences Questionnaire was dichotomized and used to measure health risk perception in smokers with (n = 67) and without schizophrenia (n = 100). A backward stepwise logistic regression was conducted using variables associated at the bivariate level to determine multivariate predictors. RESULTS: Overall, 62.5% of smokers without schizophrenia and 40.3% of smokers with schizophrenia completely recognize the health risks of smoking (p ≤ .01). Multivariate predictors for smokers without schizophrenia included: sex (Exp (B) = .3; p < .05), Smoking Consequences Questionnaire state enhancement (Exp (B) = .69; p < .01), and craving relief (Exp (B) = 1.8; p < .01). Among smokers with schizophrenia, predictors were education (Exp (B) = .7; p < .05), nicotine dependence (Exp (B) = .5; p < .01), motivation to quit (Exp (B) = 1.8; p < .01), and Smoking Consequences Questionnaire craving relief (Exp (B) = 1.8; p < .01). CONCLUSIONS: There was overlap and differences between predictors in smokers with and without schizophrenia. Commonly used techniques for education on the health consequences of cigarettes may work in smokers with schizophrenia, but intervention efforts specifically tailored to smokers with schizophrenia might be more efficacious.

Antipsychotic Treatment and Tobacco Craving in People With Schizophrenia.

OBJECTIVE: Nicotine dependence is high in schizophrenia, and craving is known to impact relapse during quit attempts. METHODS: We compared tobacco craving in smokers with schizophrenia treated with different antipsychotics. RESULTS: Mean craving scores were lowest in participants receiving first-generation antipsychotics, although these differences were not statistically significant. Craving with clozapine was not lower than with other antipsychotics. CONCLUSIONS: Further research is needed to determine whether differences in craving exist between antipsychotic classes.

A Comparison of the Fagerström Test for Cigarette Dependence and Cigarette Dependence Scale in a Treatment-Seeking Sample of Pregnant Smokers.

INTRODUCTION: Valid and reliable brief measures of cigarette dependence are essential for research purposes and effective clinical care. Two widely-used brief measures of cigarette dependence are the six-item Fagerström Test for Cigarette Dependence (FTCD) and five-item Cigarette Dependence Scale (CDS-5). Their respective metric characteristics among pregnant smokers have not yet been studied. METHODS: This was a secondary analysis of data of pregnant smokers (N = 476) enrolled in a smoking cessation study. We assessed internal consistency, reliability, and examined correlations between the instruments and smoking-related behaviors for construct validity. We evaluated predictive validity by testing how well the measures predict abstinence 2 weeks after quit date. RESULTS: Cronbach's alpha coefficient for the CDS-5 was 0.62 and for the FTCD 0.55. Measures were strongly correlated with each other, although FTCD, but not CDS-5, was associated with saliva cotinine concentration. The FTCD, CDS-5, craving to smoke, and withdrawal symptoms failed to predict smoking status 2 weeks following the quit date. CONCLUSIONS: Suboptimal reliability estimates and failure to predict short-term smoking call into question the value of including either of the brief measures in studies that aim to explain the obstacles to smoking cessation during pregnancy.

Black Cigarette Smokers Report More Attention to Smoking Cues Than White Smokers: Implications for Smoking Cessation.

INTRODUCTION: Black cigarette smokers have lower rates of smoking cessation compared with Whites. However, the mechanisms underlying these differences are not clear. Many Blacks live in communities saturated by tobacco advertisements. These cue-rich environments may undermine cessation attempts by provoking smoking. Moreover, attentional bias to smoking cues (attention capture by smoking cues) has been linked to lower cessation outcomes. Cessation attempts among Blacks may be compromised by attentional bias to smoking cues and a cue-rich environment. METHOD: Attention to smoking cues in Black and White smokers was examined in 2 studies. In both studies, assessments were completed during 2 laboratory visits: a nonabstinent session and an abstinent session. In study 1, nontreatment-seeking smokers (99 Whites, 104 Blacks) completed the Subjective Attentional Bias Questionnaire (SABQ; a self-report measure of attention to cues) and the Smoking Stroop task (a reaction time measure of attentional bias to smoking cues). In study 2, 110 White and 74 Black treatment-seeking smokers completed these assessments and attempted to quit. RESULTS: In study 1, Blacks reported higher ratings than Whites on the SABQ (p = .005). In study 2, Blacks also reported higher ratings than Whites on the SABQ (p = .003). In study 2, Blacks had lower biochemical-verified point prevalence abstinence than Whites, and the between-race difference in outcome was partially mediated by SABQ ratings. CONCLUSION: Blacks reported greater attention to smoking cues than Whites, possibly due to between-race differences in environments. Greater attention to smoking cues may undermine cessation attempts.

Validation of the French version of the marijuana craving questionnaire (MCQ) generates a two-factor model.

BACKGROUND: Craving is a major issue in drug addiction, and a target for drug treatment. The Marijuana Craving Questionnaire-Short Form (MCQ-SF) is a useful tool for assessing cannabis craving in clinical and research settings. OBJECTIVE: To validate the French version of the MCQ-SF (FMCQ-SF). METHODS: Young adult cannabis users not seeking treatment (n = 679) completed the FMCQ-SF and questionnaires assessing their frequency of cannabis use and craving, cannabis use disorder criteria, and alcohol use. RESULTS: Confirmatory factor analysis of the four-factor FMCQ-SF model did not fit the data well. Exploratory factor analysis suggested a two-factor solution ("pleasure", characterized by planning and expectation of positive effects, and "release of tension", characterized by relief from anxiety, nervousness, or tension) with good psychometric properties. This two-factor model showed good internal and convergent validity and correlated with cannabis abuse and dependence and with frequency of cannabis use and craving. CONCLUSION: Validation of the FMCQ-SF generated a two-factor model, different from the four-factor solution generated in English language studies. Considering that craving plays an important role in withdrawal and relapse, this questionnaire should be useful for French-language addiction professionals.

Nicotine enhances alerting, but not executive, attention in smokers and nonsmokers.

INTRODUCTION: Difficulty concentrating is a symptom of nicotine withdrawal that can contribute to relapse in individuals trying to quit smoking. The purpose of this study was to determine the effects of nicotine on executive and alerting attention in smokers and nonsmokers. METHODS: Thirty daily smokers who were not tobacco deprived and 30 nonsmokers participated in the study. Participants received a single dose of intranasal nicotine (0, 0.5, or 1.5 mg) at each of 3 experimental sessions on separate days. Participants completed subjective ratings and 3 attention tasks before and after nicotine administration. RESULTS: Nicotine had no effect on executive attention as assessed by a Rapid Serial Visual Presentation (RSVP) task or the Attention Network Test in smokers and nonsmokers. In contrast, nicotine enhanced alerting attention by decreasing errors on a Continuous Performance Test (CPT) in nonsmokers and improving the correct identification of target words on the RSVP task in smokers. Nonsmokers were more sensitive than smokers to the subjective, but not the cardiovascular, effects of nicotine. CONCLUSIONS: The acute administration of intranasal nicotine improved alerting attention in nonsmokers as measured by the CPT, and in smokers as measured by the RSVP. Understanding the elements of attention enhanced by nicotine might guide the development of novel medications for tobacco dependence.

Dose-response effects of spectrum research cigarettes.

INTRODUCTION: Experimental cigarettes are needed to conduct studies examining the effects of varying doses of nicotine content on smoking behavior. The National Institute on Drug Abuse contracted with Research Triangle Institute to make such cigarettes available to researchers. The goal of this study was to determine whether cigarettes that vary in nicotine content produce an expected dose-response effect. METHOD: Two studies were conducted. The first study recruited subjects from 3 sites and consisted of a single, within-subject laboratory session. Subjects first smoked 4 puffs on their usual-brand cigarette and then in double-blind, random-order, smoked 4 puffs on each experimental cigarette that contained either low nicotine (LN, 0.4 mg/g), intermediate nicotine (IN, 5.7-5.8 mg/g), or high nicotine (HN, 11.4-12.8 mg/g). Each puffing bout was separated by a 30-min interval. Subjects completed questionnaires and were assessed for vital signs after each cigarette. The second study involved 1 site and used a between-subject design in which subjects were assigned to 1 of the 3 experimental cigarettes for 1 week. Subjective responses and biomarkers of exposure were assessed. RESULTS: In the first study, significant dose-response effects were observed, particularly between the LN and HN cigarettes. The second study showed decreases in cigarette smoking and exposure biomarkers predominantly in the LN group, with no changes in the HN cigarette group. CONCLUSIONS: These results are similar to those observed in prior literature, confirming that these experimental cigarettes can be used safely and with the expected pharmacological effects.

Effects of the cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study.

Weight gain is a major adverse effect of several second-generation antipsychotic medications. Rimonabant is a cannabinoid-1 receptor antagonist that promotes weight loss in the general population. We conducted a 16-week, double-blind, placebo-controlled study of rimonabant (20 mg/d) in people with schizophrenia or schizoaffective disorder, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, who were clinically stable on second-generation antipsychotics. Participants had a body mass index of 27 kg/m or higher with hyperlipidemia or body mass index of 30 kg/m or higher, and no current substance abuse/dependence (except nicotine), more than weekly cannabis use, or recent depressive symptoms/suicidality. An exercise and dietary counseling group was offered weekly. Target enrollment was 60; the trial was terminated early because of withdrawal of rimonabant from the European market. Fifteen participants were randomized (7 rimonabant, 8 placebo); 5 completed in each group. Rimonabant was associated with a greater reduction in Brief Psychiatric Rating Scale total score versus placebo (mean ± SE difference, -1.9 ± 0.8, P = 0.02), driven by differences in the Brief Psychiatric Rating Scale anxiety/depression (-1.4 ± 0.35, P = 0.0004) and hostility (-0.7 ± 0.3, P = 0.02) factors. Group differences were not significant for the Calgary Depression Scale total score (P = 0.24), Scale for the Assessment of Negative Symptoms total score (P = 0.13), weight, blood pressure, or fasting lipids or glucose. Rimonabant was well tolerated with no significant adverse events. No significant weight loss, metabolic effects, or adverse psychiatric effects were associated with the cannabinoid-1 receptor antagonist rimonabant in this small sample of people with schizophrenia. The endocannabinoid system remains a promising target for pharmacotherapy of schizophrenia and obesity.

Oral fluid nicotine markers to assess smoking status and recency of use.

INTRODUCTION: Oral fluid collection is noninvasive and easily observed making it an attractive matrix for objectively determining smoking status. Despite large intersubject variability, cotinine oral fluid concentrations correlate with cigarettes smoked per day (CPD). Few studies, however, assessed nicotine markers in oral fluid other than cotinine; other markers might improve smoking status assessment and/or time of last cigarette. MATERIALS AND METHODS: Smoking histories and oral fluid specimens were collected from nontreatment-seeking light (1-10 CPD) and heavy smokers (greater than 10 CPD) and from environmentally exposed and nonexposed nonsmokers who provided written informed consent for this Institutional Review Board-approved study. Nicotine, cotinine, hydroxycotinine (OH-cotinine), and norcotinine oral fluid concentrations were quantified by liquid chromatography tandem mass spectrometry. RESULTS: Comparison of 1, 3, and 10 ng/mL oral fluid liquid chromatography tandem mass spectrometry cutoffs demonstrated that 10-ng/mL cutoffs performed optimally for cotinine, OH-cotinine, nicotine, and norcotinine identifying 98%, 97%, 88%, and 15% of self-reported smokers; 1% nonsmokers had greater than 10 ng/mL cotinine. No self-reported nonsmoker had greater than 10 ng/mL OH-cotinine, nicotine, or norcotinine. Norcotinine was only identified in smokers' oral fluid. Oral fluid nicotine, cotinine, and nicotine/cotinine ratios were correlated with time of last smoking (r = -0.53, -0.23, and -0.51; P < 0.05) and CPD (r = 0.35, 0.26, and 0.33; P < 0.01), respectively. DISCUSSION AND CONCLUSION: OH-cotinine performed slightly better than cotinine for distinguishing smokers from nonsmokers and should be considered as an additional oral fluid smoking indicator. Further research is required to determine if oral fluid norcotinine is a marker for distinguishing light and heavy smokers. Moderate correlations suggest nicotine, cotinine, and nicotine/cotinine ratios may be useful for determining smoking recency in "spot samples" collected during nicotine cessation treatment.

The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers.

INTRODUCTION: The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse-like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. METHODS: The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue-elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue-reactivity procedure measured cue-elicited craving. RESULTS: These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue-elicited craving, suggesting a lack of influence in cue reactivity. CONCLUSION: Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes.

Validity of the 12-item French version of the Tobacco Craving Questionnaire in treatment-seeking smokers.

INTRODUCTION: The French version of the Tobacco Craving Questionnaire (FTCQ) is a valid and reliable 47-item self-report instrument that assesses tobacco craving in four factors: emotionality, expectancy, compulsivity, and purposefulness. For use in research and clinical settings, we constructed a 12-item version of the FTCQ (FTCQ-12). METHOD: The FTCQ-12 was administered to treatment-seeking French smokers (n = 310) enrolled in the Adjustment of DOses of NIcotine in Smoking Cessation (ADONIS) trial. We conducted confirmatory factor analysis (CFA) and examined congruence in factor loadings between the FTCQ and FTCQ-12 to determine the validity and reliability of the FTCQ-12. Measures of tobacco craving, withdrawal, smoking patterns, and smoking history were included to explore the concurrent validity of the FTCQ-12. We used craving scores to distinguish participants who were highly dependent on nicotine from those less dependent on nicotine. RESULTS: CFA indicated excellent fit for a four-factor model, with congruence coefficients indicating moderate similarity in factor patterns and loadings between the FTCQ and FTCQ-12. Individual factors of the FTCQ-12 correlated positively with smoking history and withdrawal variables. Participants who were highly dependent on nicotine were nearly six times more likely to score >5 on the General Craving Score (maximum: 7) than those less dependent on nicotine. DISCUSSION: Findings suggest that the FTCQ-12 measures the same four factors as the FTCQ and TCQ, and these four constructs have unique properties. The FTCQ-12 yields valid and reliable indices of tobacco craving and has potential clinical utility for rapid assessment of tobacco craving in smokers seeking treatment.

Puffing behavior during the smoking of a single cigarette in tobacco-dependent adolescents.

INTRODUCTION: Adult and adolescent smokers regulate their nicotine and smoke intake by smoking low-yield cigarettes more intensely than high-yield cigarettes. One likely mechanism of nicotine regulation is altered puffing topography, which has been demonstrated in adult smokers. The purpose of this study was to examine the pattern of puffing behavior during the smoking of a single cigarette in adolescents. METHODS: Tobacco-dependent adolescents (n = 89) were enrolled in a treatment trial testing the efficacy of nicotine replacement therapy. About 1 week before their quit date, participants smoked ad libitum one of their usual brand of cigarettes during a laboratory session. Smoking topography measures included puff volume, puff duration, puff velocity, and interpuff interval. RESULTS: Controlling for sex, race, and number of puffs, puff volume and puff duration decreased 12.8% and 24.5%, respectively, from the first 3 to the last 3 puffs. Puff velocity and interpuff interval increased 14.8% and 13.5%, respectively. Puff volume was positively correlated with puff duration and puff velocity, whereas puff duration and puff velocity were negatively correlated. However, none of the topography measures were correlated with smoking history variables. DISCUSSION: These results suggest that adolescent smokers, like adults, are able to regulate smoke and nicotine intake on a puff-by-puff basis, therefore indicating that this aspect of smoking control is acquired early in the tobacco-dependence process.

Breath carbon monoxide and semiquantitative saliva cotinine as biomarkers for smoking.

OBJECTIVE: As a biomarker of smoking, semiquantitative analysis of cotinine (NicAlert) offers several advantages over breath carbon monoxide (CO) and quantitative analysis of cotinine. Recent studies have used urine NicAlert and breath CO in combination to verify abstinence. However, no studies have evaluated the performance of saliva NicAlert against or in combination with breath CO. METHOD: Breath CO, saliva NicAlert, and smoking history were compared in an urban population of daily smokers (n = 24) and nonsmokers (n = 25). RESULTS: Saliva NicAlert predicted self-reported smoking with 100% sensitivity and 96% specificity. At a cutoff of > 5 ppm, breath CO had 100% sensitivity and 100% specificity in predicting self-reported smoking. Breath CO was positively correlated with saliva NicAlert and negatively correlated with minutes since last cigarette. CONCLUSION: Saliva NicAlert had high sensitivity and specificity in identifying daily smokers. Compared to saliva NicAlert, breath CO level was more indicative of recent smoking. Future treatment studies should evaluate the performance of saliva NicAlert as an alternative to the urine test.

Sociodemographic characteristics of cannabis smokers and the experience of cannabis withdrawal.

BACKGROUND: Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. OBJECTIVES: Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. METHODS: Retrospective self-report of a "serious" cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionnaire. RESULTS: Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99-10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence.

Exploring the role of the Ser9Gly (rs6280) Dopamine D3 receptor polymorphism in nicotine reinforcement and cue-elicited craving.

Preclinical studies show that the dopamine D3 receptor (D3R) is involved in the reinstatement of drug seeking and motivation for drugs of abuse. A D3R gene variant, Ser9Gly (rs6280) has been linked to nicotine dependence, yet the mechanisms underlying its involvement in nicotine dependence is unclear. This study investigated the relationship between the Ser9Gly variant and measures of both nicotine reinforcement and cue-elicited craving. Phenotypes of smoking behaviors were assessed in genetically grouped (Glycine vs. No Glycine carriers) current smokers (n = 104, ≥ 10 cigarettes per day). Laboratory measures included a forced choice session (to measure reinforcement of nicotine containing vs. denicotinized cigarettes), and a cue-reactivity session (to measure smoking cues vs. neutral cues elicited craving). The forced choice procedure revealed that subjective ratings were significantly higher in response to nicotinized compared to denicotinized cigarettes; however the Ser9Gly variant did not influence this effect. By comparison, smoking cues elicited greater craving over time compared to neutral cues, and Glycine carriers of the Ser9Gly D3R variant seem to experience a significant blunted cue-elicited craving effect. Results support D3R involvement in nicotine cue reactivity. However, more research is needed to reveal how this gene variant modulates various aspects of nicotine dependence.

Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray.

The discovery of the role of nicotinic receptors in attention and memory has led to the testing of nicotinic analogs as cognitive enhancing agents in patient populations. Empirical information about nicotine's ability to enhance elements of attention and memory in normal individuals might guide development of therapeutic uses of nicotine in cognitively impaired populations. The purpose of this study was to determine the effect of nicotine on continuous attention, working memory, and computational processing in tobacco-deprived and nondeprived smokers. A total of 28 smokers (14 men, 14 women) participated in a double-blind, placebo-controlled, within-subject study, in which they were overnight (12 h) tobacco deprived at one session and smoked ad libitum before the other session. At each session, participants received 0, 1, and 2 mg nicotine via nasal spray in random order at 90 min intervals. Before and after each dose, a battery of cognitive, subjective, and physiological measures was administered, and blood samples were taken for plasma nicotine concentration. Overnight tobacco deprivation resulted in impaired functioning on all cognitive tests and increased self-reports of tobacco craving and negative mood; nicotine normalized these deficits. In the nondeprived condition, nicotine enhanced performance on the continuous performance test (CPT) and an arithmetic test in a dose-related manner, but had no effect on working memory. In general, women were more sensitive than men to the subjective effects of nicotine. These results provide an unequivocal determination that nicotine enhanced attentional and computational abilities in nondeprived smokers and suggest these cognitive domains as substrates for novel therapeutic indications.

Divided versus selective attention: evidence for common processing mechanisms.

The current study revisited the question of whether there are brain mechanisms specific to divided attention that differ from those used in selective attention. Increased neuronal activity required to simultaneously process two stimulus dimensions as compared with each separate dimension has often been observed, but rarely has activity induced by a divided attention condition exceeded the sum of activity induced by the component tasks. Healthy participants performed a selective-divided attention paradigm while undergoing functional Magnetic Resonance Imaging (fMRI). The task required participants to make a same-different judgment about either one of two simultaneously presented stimulus dimensions, or about both dimensions. Performance accuracy was equated between tasks by dynamically adjusting the stimulus display time. Blood Oxygenation Level Dependent (BOLD) signal differences between tasks were identified by whole-brain voxel-wise comparisons and by region-specific analyses of all areas modulated by the divided attention task (DIV). No region displayed greater activation or deactivation by DIV than the sum of signal change by the two selective attention tasks. Instead, regional activity followed the tasks' processing demands as reflected by reaction time. Only a left cerebellar region displayed a correlation between participants' BOLD signal intensity and reaction time that was selective for DIV. The correlation was positive, reflecting slower responding with greater activation. Overall, the findings do not support the existence of functional brain activity specific to DIV. Increased activity appears to reflect additional processing demands by introducing a secondary task, but those demands do not appear to qualitatively differ from processes of selective attention.