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RationaleGiven that tetrahydrocannabinol (THC) and nicotine have similar effects on negative affect (NA), we hypothesized that a 7-mg nicotine patch (NP) would reduce NA-related cannabis (CAN) withdrawal symptoms in cannabis-dependent (CD) individuals who were not nicotine dependent.ObjectiveWe sought to determine whether NP reduces NA across 15 days of CAN abstinence in two groups: non-tobacco smokers (NTS) and light tobacco smokers (LTS).MethodsCD participants (N = 127; aged 18–35) who used CAN at least 5 times/week for the past 12 + months were randomized to (1) NP or (2) a placebo patch (PP) and received $300 for sustained biochemically verified CAN abstinence. Of those randomly assigned, 52 of 63 NP, and 56 of 64 PP maintained biochemically verified CAN abstinence and 51 NP and 50 PP participants complied with all aspects of the study. Affect and other withdrawal symptoms were measured every 48 h across 15 days of CAN abstinence.ResultsAfter controlling for age, tobacco use, baseline THC concentration, and baseline measurements of the dependent variable, NP reduced NA symptoms across the 15-day treatment relative to PP. Differences in NA and CAN withdrawal symptoms were not moderated by tobacco user status.ConclusionsThe findings provide the first evidence that NP may be able to attenuate NA-related withdrawal symptoms in individuals with cannabis use disorder who are not heavy users of tobacco or nicotine.Clinical trials registryNCT01400243 http://www.clinicaltrials.gov

RationaleThere is strong evidence that nicotine can enhance cognitive functions and growing evidence that this effect may be larger in young healthy APOE ε4 carriers. However, the moderating effects of the APOE ε4 allele on cognitive impairments caused by nicotine deprivation in chronic smokers have not yet been studied with brain indices.ObjectiveWe sought to determine whether young female carriers of the APOE ε4 allele, relative to noncarriers, would exhibit larger abstinence-induced decreases in P3b amplitude during a two-stimulus auditory oddball task.MethodsWe compared parietal P3bs in female chronic smokers with either APOE ε3/ε3 (n = 54) or ε3/ε4 (n = 20) genotype under nicotine-sated conditions and after 12–17-h nicotine deprivation.ResultsNicotine deprivation significantly reduced P3b amplitudes in APOE ε4 carriers, but not in APOE-ε3/ε3 individuals, such that the difference seen prior to nicotine deprivation was eliminated.ConclusionsThe results suggest that subjects with the APOE ε4 allele are more sensitive to nicotine, which could influence smoking patterns, the risk for nicotine dependence, and the cognitive effects of nicotine use in these individuals.

Objective This study aimed to examine the associations of individual trajectories of three types of negative affect (NA: anxiety, depression, and anger) and craving during a 44-day period of incentivized smoking abstinence period with cessation outcome at 3 months and at 1 year. Methods Adult smokers ( N  = 140) completed questionnaire assessments of NA and craving during pre-quit baseline sessions and 15 postquit sessions over the 45 days of biochemically verified abstinence while on nicotine or placebo patch treatment. Growth curve and logistic regression analyses were used to examine the associations of trajectory parameters of the individual NA states and craving with the abstinence outcomes at 3 months and 1 year postquit. Results Greater declines in anxiety, depression, and anger symptoms over the first 44 days of smoking cessation were predictive of higher odds of abstinence at both 3 months and 1 year. Moreover, the greater declines in anxiety and anger remained as significant predictors of abstinence at both time points, independent of the predictive ability of the trajectory profiles of craving. Conclusions The findings suggest that slower dissipation of NA, especially anxiety and anger, represents a greater risk for relapse to smoking beyond that predicted by craving during early abstinence. Thus, temporal profiles of the affective symptoms convey unique motivational significance in relapse. Reduction in NA during early abstinence may be a valid target for interventions to increase long-term cessation success rates particularly among individuals with refractory affective symptoms.

Much research testing positive psychological interventions (PPIs) has focused primarily on emotional states, while research testing the effects of positive attention bias modification (PABM) has tended to focus primarily on attentional deployment. Evidence is sparse and inconsistent on attentional deployment (i.e., a process of emotion regulation) in PPIs, changes in emotional states (i.e., an outcome of emotion regulation) in PABM programs, and the combined effects of the two types of interventions on attentional deployment and emotional states. In the current study, we found that the gratitude letter increased positive affect immediately after completion and the PABM biased attention immediately after completion; however, the effects of the gratitude letter on affect were only maintained throughout the study when paired together with the PABM program. Further, we found evidence that the gratitude letter and the gratitude letter with the PABM program increases initial viewing away and late viewing towards emotional stimuli. Thus, the gratitude letter may produce positive effects on affect by increasing the salience of emotional stimuli, potentially helping individuals notice positive sitmuli in their enviroment to maintain their mood and negative stimuli in their enviornment to reduce emotional avoidance. The results suggest that combining the gratitude letter with a PABM program can produce strong effects on both attentional deployment and emotional states. We discuss the implications for clinical practice and future research.

Aversive and smoking-related stimuli are related to smoking urges and relapse and can be potent distractors of selective attention. It has been suggested that the beneficial effect of nicotine replacement therapy may be mediated partly by the ability of nicotine to reduce distraction by such stimuli and thereby to facilitate attention to task-relevant stimuli. The present study tested the hypothesis that nicotine reduces distraction by aversive and smoking-related stimuli as indexed by the parietal P3b brain response to a task-relevant target digit. We assessed the effect of nicotine on distraction by emotionally negative, positive, neutral, and smoking-related pictures immediately preceding target digits during a rapid visual information processing task in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included two experimental sessions. After overnight smoking deprivation (12+hr), active nicotine patches were applied to participants during one of the sessions and placebo patches were applied during the other session. Nicotine enhanced P3b responses associated with target digits immediately subsequent to negative emotional pictures bilaterally and subsequent to smoking-related pictures only in the right hemisphere. No effects of nicotine were observed for P3bs subsequent to positive and neutral distractor pictures. Another measure of attention, contingent negative variation amplitude in anticipation of the target digits also was increased by nicotine, especially in the left hemisphere and at posterior sites. Together, these findings suggest that nicotine reduces the distraction by emotionally negative and smoking-related stimuli and promotes attention to task-related stimuli by modulating somewhat lateralized and task-specific neural networks.

Introduction: TaqIA polymorphism, a genetic variant associated with the expression level of dopamine D2 receptors in the brain, has been linked to various aspects of smoking behavior, including smoking prevalence, affective withdrawal symptoms, and smoking cessation outcome. However, its involvement in motivation to smoke cigarettes has not been elucidated. Methods: The present study examined the possible differences in self-reported reasons to smoke and craving for smoking in 160 smokers participating in a clinical trial. Results: Individuals with at least one A1 allele of the TaqIA polymorphism were more likely to report smoking for stimulating effects and to reduce negative affect compared with those lacking an A1 allele. The association of the A1 genotype with a higher probability and stronger motive to smoker to enhance cognitive functioning was evident in female but not in male smokers. Female A1 carriers also expected a greater likelihood of smoking for pleasure than those without an A1 allele. A1 subjects reported stronger craving for cigarettes during early days and the last phase of a 6-week abstinence period. Discussion: These results support the idea that dopaminergic transmission plays an important role in the neurobiological basis of reasons for smoking and that the TaqIA variant is one of the genetic factors underlying individual differences in these aspects. These findings also have implications for improving treatment strategies to help individuals quit smoking by controlling their motivation to continue cigarette consumption.

The present study examined the hypothesis that nicotine is associated with reduced attentional bias to affective and smoking-related stimuli in a modified Stroop task. A total of 56 habitual smokers were each tested on 4 days with 14 mg nicotine patches and placebo patches, counterbalanced, as a within-subjects factor in a double-blind design. A modified Stroop using negative-affect words, smoking words, color words, and neutral words was presented via computer in blocked format. As predicted, nicotine, relative to placebo, was associated with decreased attentional bias to negative words. Nicotine speeded performance during smoking-word and color-word blocks to the same degree as during neutral words and thus appeared to also have a nonspecific performance-enhancing effect. In an exploratory analysis, nicotine-attention effects occurred only in the initial presentation of pairs of blocked word pages. Nicotine also was associated with improved mood. The results are discussed in terms of affect-attention and smoking literatures.

The Situation × Trait Adaptive Response (STAR) model hypothesizes that nicotine reduces negative and enhances positive affect to a greater degree in situations involving internally driven attention, as when stressor stimuli are distal (past or future), thereby allowing nicotine-primed biasing of attentional processing away from negative and toward positive stimuli. To test this hypothesis, the effects of nicotine were assessed in 64 smokers and 64 never-smokers, half of whom viewed emotionally negative pictures in a no-choice picture attention task that required them to focus on the picture stressors. The other half viewed the same stimuli in a two-choice picture attention task that presented stressor pictures in one visual field and simultaneously presented positive or neutral pictures in the other visual field. Participants received a nicotine patch during one session and a placebo patch during the other session. Nicotine modulated affect only in smokers. In smokers, compared with placebo, nicotine patch reduced negative affect more during the distal periods (between stressors) than during actual stressor exposure and in women reduced negative affect more when the proportion of negative stimuli was low. Nicotine also enhanced positive affect more during distal than proximal stressors. Nicotine tended to reduce eye-gaze at negative pictures, especially when the alternative picture was positive. The overall findings are consistent with the view that nicotine biases attention away from negative stimuli when equally salient positive or benign stimuli are present.

The effects of nicotine, distractor type, and dopamine type-2 receptor (DRD2) genotype on rapid visual information processing (RVIP) task performance were assessed in habitual smokers. Four RVIP tasks differed in terms of distractor location (central vs. peripheral) and distractor type (numeric vs. emotional). Each participant performed each of the tasks on two different days, once while wearing an active nicotine patch and once while wearing a placebo patch. Overall, the nicotine patch produced more accurate detection of and faster reaction times to target sequences; however, these effects varied with distractor type and genotype. Nicotine speeded reaction time more with left-visual-field (LVF) than right-visual-field (RVF) emotional distractors but speeded reaction time more with RVF than LVF numeric distractors, especially when the distractor digit matched the target sequence in terms of numeric oddness or evenness. Nicotine tended to facilitate performance more in individuals with at least one A1 allele than in homozygous A2A2 individuals, especially with numeric distractors presented to the left hemisphere. Nicotine tended to reduce distraction by negative stimuli more than other types of stimuli. Few gender differences were observed. The overall pattern of results was consistent with the view that nicotine modulates selective attention or subsequent information processing in a manner that depends partly on the emotional versus numeric nature of task distractors, DRD2 genotype, and the brain hemisphere that initially processes the distractors (visual field of distractor).

Background: A growing number of studies have assessed the effects of acute nicotine on affect, cognition, and brain activity in never-established smokers in attempts to identify mechanisms by which nicotine promotes progression to dependence. However, these acute administration studies have not adequately addressed the problem of potential adverse side effects due to lack of tolerance, such as nausea, feelings of sickness, lightheadedness, and general negative affect and malaise - a term referred to as nicotine overdose events (NODEs). Thus, we report the first study to carefully characterize the prevalence, intensity, and effects of NODEs in never-established-smokers after acute nicotine administration. Methods: We compared the subjective effects of two different 7 mg nicotine patches that have different pharmacokinetics on never-established smokers ( n = 67). One patch produces gradual increases in blood nicotine and the other produces more rapid increases in blood nicotine. Results: The findings suggest that in never-smokers, the lowest dose (7 mg) of rapid blood nicotine-rise patches are associated with a high prevalence of NODEs (45.83%) and decreased positive affect (PA) (54.17%) compared to a placebo patch (8.34% for NODEs and 33.34% for PA). The slow-rise patch did not significantly affect nicotine overdose symptoms or PA. Conclusions: Fast blood-rise nicotine patches may not be an ecologically valid method of nicotine delivery to never-smokers, while slow-rise nicotine patches, lower dose, and self-paced dosing may be more appropriate in this population. Findings also highlight the importance of the careful assessment of NODES in this population.