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.

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'.

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.

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.

Nicotine Intake in Pregnant Smokers and a General Population of Smokers.

OBJECTIVE: The purpose of this study was to assess whether pregnant smokers have the same nicotine intake from cigarettes as a general population of smokers and whether the known lower daily cigarette consumption among pregnant smokers is associated with higher nicotine intake among pregnant smokers. METHOD: The study was a cross-sectional comparison of pregnant smokers and a general population of smokers in smoking cessation clinics. Participants were treatment-seeking pregnant (n = 476), nonpregnant female (n = 116), and male (n = 195) smokers who participated in two independent smoking cessation trials. Nicotine intake was measured as saliva cotinine/ cigarette/kg body weight ratio. RESULTS: The mean saliva cotinine (µg/L)/ cigarette/kg body weight (0.21, SD = 0.15) of pregnant smokers was similar to that of nonpregnant female smokers (0.24, SD = 0.14) and higher than that of male smokers (0.18, SD = 0.12, p = .002) despite a substantially lower number of cigarettes per day (pregnant smokers: 12, SD = 6; nonpregnant female smokers: 26.6, SD = 11.7; male smokers: 23.5, SD = 9.5, p < .001). Among pregnant smokers, saliva cotinine, as expected, increased in parallel with the number of cigarettes per day, but nicotine intake (cotinine/cigarette/kg body weight) was inversely associated with daily cigarette consumption (p < .001). No association between cigarettes per day and nicotine intake was observed in male and nonpregnant female smokers (p = .43). CONCLUSIONS: This secondary analysis showed that pregnant smokers' nicotine intake was similar to that of a general population of smokers despite a lower cigarette consumption rate. Among pregnant smokers, lower daily cigarette consumption was associated with higher nicotine intake from cigarettes, suggesting compensatory smoking.

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.

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.

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.

Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-Pregnant Smokers.

Although pregnant smokers are aware of the negative peri- and postnatal health consequences of smoking, the cessation rate in pregnancy is low, raising the question of why pregnant smokers have difficulty quitting. Reasons might be that pregnant smokers experience more intense craving and withdrawal symptoms than non-pregnant smokers. We compared craving and withdrawal in 306 pregnant smokers versus 93 non-pregnant women using data from two smoking cessation trials. Complete data were analyzed using pre-quit and post-quit (2 weeks after quit date) craving and withdrawal measured by the 12-item French Tobacco Craving Questionnaire (FTCQ-12) and French Minnesota Nicotine Withdrawal Scale (FMNWS). Pregnant smokers started smoking and smoked regularly earlier and succeeded far less at quitting smoking by week 2 than the general population of smokers (11% versus 43%). Post-quit date FTCQ-12 general score was higher in pregnant smokers compared to comparison groups, and was driven by elevated emotionality and expectancy. FMNWS decreased significantly less among pregnant smokers than among non-pregnant smokers. Insufficient reduction of craving and withdrawal symptoms in response to a quit attempt may partially explain why pregnant smokers may have more difficulty quitting than non-pregnant smokers. Because this was a historical comparison, findings are preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms in pregnant versus non-pregnant smokers.

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.

Cross validation of the prognostic and diagnostic utility of tobacco craving in a general and a pregnant sample of treatment-seeking smokers.

BACKGROUND: Valid and reliable brief measures of tobacco craving are necessary for research and clinical purposes. However, comparisons of the utility of single-item and brief multidimensional craving measures are scarce. METHODS: We analyzed two tobacco craving measures, the French versions of the 12-item Tobacco Craving Questionnaire (FTCQ-12) and the single craving item on the Minnesota Nicotine Withdrawal Scale, in pregnant and non-pregnant (females and males) French smokers from two independent smoking cessation trials. Using data from pregnant smokers, we estimated first a prognostic model for each measure and compared their ability to predict relapse from one visit to the next. We next used cutoff values for both measures to determine how well craving distinguished current smokers from abstainers. For cross-validation, we tested how well the same cut-off values generalized to non-pregnant smokers. RESULTS: Two FTCQ-12 factors (Expectancy and Purposefulness) predicted smoking status; scores were higher in pregnant non-abstainers than abstainers. The sum of these two factors, FTCQ-12 risk score (RS), yielded higher sensitivity both in prognostic and diagnostic models than single-item MNWS craving. FTCQ-12 RS had higher sensitivity among pregnant than non-pregnant smokers. Specificity of both tobacco craving measures was similar among pregnant smokers, but higher with MNWS craving than with FTCQ-12 RS in non-pregnant smokers. CONCLUSIONS: FTCQ-12 RS and MNWS craving can be used together in clinical practice to rapidly predict smoking status. Interventions targeting Expectancy and Purposefulness may result in higher likelihood of abstinence, especially among pregnant smokers.

Subjective response to nicotine by menstrual phase.

INTRODUCTION: The luteal menstrual phase might be a favorable time for smoking cessation when non-nicotine interventions (e.g. counseling, bupropion) are used, whereas the follicular menstrual phase appears favorable when nicotine interventions are used. Thus, there may be an interaction between menstrual phase and response to nicotine. We sought to examine the role of menstrual phase on response to nicotine during acute smoking abstinence. METHODS: In this controlled cross-over trial, women completed two identical experimental sessions (follicular [F] vs. luteal [L] phase) after four days of biochemically-verified smoking abstinence. During the sessions, nicotine nasal spray was administered, and participants provided a series of subjective assessments. RESULTS: Participants (n=140) were 29.7±6.6years old and smoked 12.6±5.8 cigarettes per day. Compared to the F phase, the L phase was associated with a greater increase in stimulation (7.2±2.2 vs. 14.4±2.3, p=0.01, respectively) and greater decrease in urge to smoke (-13.6±2.3 vs. -21.1±2.5, p=0.02, respectively) after the first dose of nicotine. No other significant differences were observed. CONCLUSIONS: Out of 13 total measures examined at two different time points, we observed only two significant menstrual phase differences in the subjective response to nicotine. Therefore, these data do not provide strong evidence for a menstrual phase difference in the subjective response to nicotine. Additional research is needed to confirm this relationship and explore how non-nicotine smoking reinforcements (such as sensory sensations) may vary by menstrual phase.

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.

Mu Opioid Receptor Binding Correlates with Nicotine Dependence and Reward in Smokers.

The rewarding effects of nicotine are associated with activation of nicotine receptors. However, there is increasing evidence that the endogenous opioid system is involved in nicotine's rewarding effects. We employed PET imaging with [11C]carfentanil to test the hypotheses that acute cigarette smoking increases release of endogenous opioids in the human brain and that smokers have an upregulation of mu opioid receptors (MORs) when compared to nonsmokers. We found no significant changes in binding potential (BPND) of [11C]carfentanil between the placebo and the active cigarette sessions, nor did we observe differences in MOR binding between smokers and nonsmokers. Interestingly, we showed that in smokers MOR availability in bilateral superior temporal cortices during the placebo condition was negatively correlated with scores on the Fagerström Test for Nicotine Dependence (FTND). Also in smokers, smoking-induced decreases in [11C]carfentanil binding in frontal cortical regions were associated with self-reports of cigarette liking and wanting. Although we did not show differences between smokers and nonsmokers, the negative correlation with FTND corroborates the role of MORs in superior temporal cortices in nicotine addiction and provides preliminary evidence of a role of endogenous opioid signaling in frontal cortex in nicotine reward.

The acute tobacco withdrawal syndrome among black smokers.

Black smokers have greater difficulty quitting tobacco than White smokers, but the mechanisms underlying between-race differences in smoking cessation are not clear. One possibility is that Black smokers experience greater acute withdrawal than Whites. We investigated whether Black (n = 104) and White smokers (n = 99) differed in abstinence-induced changes in self-report, physiological, and cognitive performance measures. Smokers not wishing to quit completed two counterbalanced experimental sessions. Before one session, they abstained from smoking for at least 12 hr. They smoked normally before the other session. Black smokers reported smaller abstinence-induced changes on a number of subjective measures including the total score of the 10-item Questionnaire for Smoking Urges (QSU) and the total score of the Wisconsin Smoking Withdrawal Scale (WSWS). However, on most subjective measures, and on all objective measures, there were no between-race differences in abstinence-induced change scores. Moreover, Black participants did not report lower QSU and WSWS ratings at the abstinent session, but they did experience significantly higher QSU and WSWS ratings at the nonabstinent session. Abstinence-induced changes in subjective, physiological, and cognitive measures in White smokers were similar for smokers of nonflavored and menthol-flavored cigarettes. There was no evidence that Black smokers experienced greater acute tobacco withdrawal than Whites. To the contrary, Black participants experienced smaller abstinence-induced changes in self-reported craving and withdrawal on some measures. Racial differences in smoking cessation are unlikely to be explained by acute withdrawal.

Motivations to quit cannabis use in an adult non-treatment sample: are they related to relapse?

BACKGROUND: The majority of cannabis smokers who quit do so without formal treatment, suggesting that motivations to quit are an important part of cessation process. However, little is known about how motivations relate to successful quitting. METHOD: A convenience sample of 385 non-treatment-seeking adult cannabis smokers (58% male, age 16-64years at start of quit attempt) who made a "serious" (self-defined) quit attempt without formal treatment while not in a controlled environment were administered the 176-item Marijuana Quit Questionnaire (MJQQ) to assess their motivations to quit and outcome of the quit attempt. Exploratory factor analysis was performed to identify significant motivational factors. Subgroup comparisons used t-tests and ANOVA. Cox proportional hazard regression and the General Linear Model were performed to evaluate the influence of motivational factors, gender, and age on relapse status at time of interview and risk of relapse over time, with time between quit attempt and interview as a covariate. RESULTS: Exploratory factor analysis identified 6 motivational factors with eigenvalues >1 which accounted for 58.4% of the total variance: self-image and self-control, health concerns, interpersonal relationship concerns, legal concerns, social acceptability concerns, and self-efficacy. Women were more likely than men to be motivated by self-image/self-control, health concerns, and social acceptability concerns. Older individuals were more likely to be motivated by health concerns. At the time of interview, 339 subjects had relapsed. Self-image and self-control, health concerns, interpersonal relationship concerns, and social acceptability concerns were associated with greater likelihood of abstinence at the study interview. Legal concerns and social acceptability concerns were associated with significantly lower hazard ratios (0.88, 0.83) for relapse during the abstinent period. CONCLUSION: These findings show gender and age differences in motivations to quit cannabis smoking and that adult cannabis smokers have motivations to quite similar to those of adolescent cannabis smokers and of adults who quit alcohol and tobacco use without formal treatment. The findings suggest areas of focus to improve secondary prevention and psychosocial treatment efforts.

Predicting smoking relapse with a multidimensional versus a single-item tobacco craving measure.

BACKGROUND: Research suggests that craving is a predictor of smoking relapse. Craving can be assessed by multiple item or multifactorial scales or by single items. However, no systematic comparisons of their prognostic validity or accuracy have been published. METHODS: The French versions of the 12-item Tobacco Craving Questionnaire (FTCQ-12) and the single craving item on the Minnesota Nicotine Withdrawal Scale (MNWS) are brief, valid, and reliable self-report measures of tobacco craving. In this secondary study, we analyzed data from French smokers with health-related problems enrolled in the Adjustment of DOses of NIcotine in Smoking (ADONIS) cessation trial. We estimated prediction models for each measure and compared their ability to distinguish correctly participants who relapsed from those who did not at 1-8 weeks after their quit date. RESULTS: Adjusted for all potential confounders FTCQ-12 risk score (RS; Factor 2, Expectancy plus Factor 4, Purposefulness) and MNWS craving were valid predictors of smoking relapse at endpoints measured 1-7 weeks apart. Prognostic accuracy of FTCQ-12 RS was greatest at 1-2 weeks follow-up compared to only 1 week for MNWS craving. Sensitivity for FTCQ-12 RS and MNWS craving was 85% and 53%, respectively. CONCLUSIONS: FTCQ-12 RS suggests a relapse process involving urges and desires in anticipation of the positive benefits of smoking linked with intent and planning to smoke. Findings also suggest that FTCQ-12 RS may be a better predictor instrument for smoking relapse than MNWS craving.

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.