Facilitated extinction of conditioned fear responses by delta 9-tetrahyrdrocannabidol in humans: a pilot study.

OBJECTIVE: We sought to determine whether acute delta 9-tetrahyrdrocannabidol (THC) administration would facilitate fear extinction in young occasional cannabis users, given that animal models indicate THC facilitates extinction learning, and recent studies indicate THC administration may also enhance threat memory extinction in humans. METHODS: On each of the 2 days, 24+ hour THC-deprived participants were conditioned to fear visual stimuli in a delay conditioning and extinction paradigm. Both CS+ and CS- were faces of negative emotional valence, with the CS+ paired with mild electric shock. Throughout both conditioning and extinction paradigms, EEG was measured to quantify event-related potentials for these learning processes. Following conditioning, individuals, in a randomized and counter-balanced order, smoked either an active THC cigarette (26.25 mg/2.7% THC) or a placebo marijuana cigarette (0.002% THC) on 1 day and the opposite cigarette on the second day. After smoking, CS+ and CS- were presented without shock, resulting in extinction of conditioned fear. RESULTS: Relative to placebo, THC facilitated extinction of the conditioned response to the CS+, as reflected by reductions in late positive potential amplitude during extinction learning. CONCLUSIONS: The results indicate that acute THC administration may facilitate extinction of the conditioned fear response in humans.

Effects of Cannabis-Delivered THC on mood and negative attentional bias in the context of positive vs. neutral Alternatives-a pilot study.

OBJECTIVE: To assess: (1) the acute effects of smoked marijuana (MJ) on negative attentional bias (NAB), (2) moderation of these effects by positive versus neutral alternatives, and (3) the associations of tetrahydrocannabinol (THC)-induced changes in NAB with changes in affect. METHODS: Fourteen MJ users (1-4 uses/wk) smoked a THC cigarette on 1 day and a placebo cigarette on the other counterbalanced day. After smoking, participants freely gazed back and forth at a series of two side-by-side pictures pairs presented for 3000 ms (one negative, while the other was either positive or neutral) while eye gaze was tracked. RESULTS: The effects of THC relative to placebo varied across time such that THC increased NAB during the early temporal component of threatening picture viewing, 333-858 ms after dual-picture onset, regardless of alternative picture valance. However, contrary to the attentional bias-causes affect hypothesis, during the early viewing phase THC-enhanced positive affect (PA) correlated positively with THC-induced NAB. In contrast, during the late phase (891-3000 ms) THC-enhanced PA did not correlate significantly with NAB, though THC-induced negative affect (NA) change did correlate positively with THC-induced change in NAB in the positive alternative condition. CONCLUSIONS: We replicated findings of others showing that THC can enhance NAB during the early stages of threatening picture viewing. We extended previous results by demonstrating the THC-induced NAB is associated with increased PA during initial threat viewing, but with increased NA during later processing if positive alternatives are present.

Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers.

INTRODUCTION: Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine. METHODS: Light smokers (n = 116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence 'risk' allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured. RESULTS: Across the sample, reward responsiveness was greater following nicotine compared to placebo (p = 0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received placebo first (p = 0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p < 0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p = 0.010) and were associated with blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine. CONCLUSION: These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine's effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population. IMPLICATIONS: Individuals carrying genetic risk factors associated with nicotine dependence(rs16969968 A-allele carriers) and those with higher levels of depressive personality traits, showmore pronounced increases in reward learning following acute nicotine exposure. These findingssuggest that genetic and personality factors may drive individual differences in smoking trajectoriesin young light smokers by altering the degree to which nicotine enhances reward processing. CLINICAL TRIAL REGISTRATION: NCT02129387 (pre-registered hypothesis: www.clinicaltrials.gov).

Effects of nicotine patches on early and late attentional bias to smoking cues: We may know less than we think.

In contrast to overnight deprivation versus satiety studies, a small number of placebo-controlled studies have failed to find that nicotine administration reduces attentional bias (AB) to smoking cues. To assess the reliability of this failure and to address the duration and salience of AB in smokers versus never-smokers, we used a longer-than-typical (i.e., 3,000 ms) smoking cue-presentation time in a placebo-controlled trial of smokers and never-smokers. We aimed to assess whether a nicotine patch (i.e., active vs. placebo) attenuates continuously assessed eye gaze-measured AB to smoking cues across 3,000 ms in 32 habitual, overnight-deprived smokers and smoker-nonsmoker differences compared to 32 never-smokers. We presented a series of picture pairs (i.e., one smoking-related and one affectively neutral control picture) simultaneously to assess AB. Participants attended a 14 mg nicotine patch and a placebo patch session in a randomized order. The habitual smokers were 12-18 hr nicotine-deprived during both sessions. Smokers demonstrated a stronger AB toward smoking cues than never-smokers across the entire 3,000 ms cue-presentation time. Nicotine did not significantly reduce the AB to smoking cues but the AB was strongly and positively related to deprivation-associated cravings in smokers. Patch-delivered nicotine did not reduce AB to smoking cues presented for up to 3,000 ms, even though smoker-nonsmoker differences in bias remained. Assessments of longer cue presentations and more subtle cues may provide nuance not currently captured by existing studies, because of potential demand effects in designs that contrast overnight versus sated state effects on AB. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

APOE genotype influences P3b amplitude and response to smoking abstinence in young adults.

RATIONALE: There 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. OBJECTIVE: We 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. METHODS: We 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. RESULTS: Nicotine 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. CONCLUSIONS: The 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.

Nicotine patch for cannabis withdrawal symptom relief: a randomized controlled trial.

RATIONALE: Given 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. OBJECTIVE: We 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). METHODS: CD 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. RESULTS: After 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. CONCLUSIONS: The 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 REGISTRY: NCT01400243 http://www.clinicaltrials.gov.

DRD2-related TaqIA polymorphism modulates motivation to smoke.

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.

Serotonin transporter genotype and depressive symptoms moderate effects of nicotine on spatial working memory.

Smokers may use nicotine to self-medicate for situation-specific or person-specific cognitive or affective deficits. Although evidence suggests that nicotine replacement therapy (NRT), relative to placebo, enhances spatial working memory (SWM) in smoking-abstinent smokers with schizophrenia, the extent to which NRT may be helpful in attenuating abstinence-related SWM in other groups with deficits in SWM is unknown. Depressive symptoms are associated with both tobacco smoking and deficits in SWM. Previous studies have found that smoking abstinence increases depressive affect and depression-related hemispheric asymmetries in brain activation. Although the serotonin neurotransmitter system is closely associated with depression and the effects of nicotine, the authors are not aware of any studies that have evaluated the possible role of individual differences in serotonin transporter (5-HTT) genotype and depressive symptoms as moderators of the effects of NRT on SWM. Thus, the current study assessed the effects of NRT (nicotine patch) on SWM in relation to: (1) depressive traits and (2) 5-HTT genotype. Smoking-deprived habitual smokers (N = 64) completed the dot recall test of SWM during counterbalanced and double-blind nicotine and placebo testing sessions. There was a marginal overall effect of NRT on SWM. More importantly, NRT enhanced SWM in 5-HTT short allele carriers, relative to those with two long alleles, and this enhancement in short-allele carriers was greater for individuals with higher levels of depressive symptoms.

Smoking abstinence symptoms across 67 days compared with randomized controls-Moderation by nicotine replacement therapy, bupropion, and negative-affect traits.

Accurate knowledge of negative affect (NA)-related smoking abstinence symptoms (SAS) severity and duration and their moderation by pharmacotherapy and NA-related personality traits is critical for efficacious treatments given that elevated state and trait NA are predictors of relapse. However, SAS severity, duration, and moderation are not well characterized. To date, the longest randomized controlled trial (RCT) of NA-related SAS using randomized delayed-quit smoking controls only examined symptoms across 45 days, despite clinical evidence that SAS may last longer. The present RCT assessed SAS across 67 days in dependent smokers (N = 95) who were randomized either to quit or to delay quitting for the course of the trial. The quit group was further randomized to receive either nicotine replacement therapy (NRT), bupropion (BUP), or placebo. Abstinence-related increases in anger-irritability, depressive, anxiety, and general NA symptoms did not resolve relative to the delayed quit group (DQG) levels across the 67 days in any of the 3 quit groups, though craving fell to below DQG and prequit levels. While NRT attenuated Day 3 SAS relative to BUP and placebo, BUP and NRT generally did not reduce SAS. High scores on trait measures of NA/neuroticism predicted greater increases in and duration of NA-related SAS, potentially indicating that smoking abstinence unmasks affective symptoms. Positive affect was not impacted by abstinence or treatment. The results support the views that (a) prequit baseline values are not a valid index of NA SAS recovery, and (b) on average, NA-related SAS take longer than 67 days to resolve. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Emotional stimuli and context moderate effects of nicotine on specific but not global affects.

The authors tested the hypothesis that the effects of nicotine on affect are moderated by the presence or absence of emotionally positive and negative stimuli and by attentional choice to avoid attending to emotionally negative stimuli. Thirty-two habitual smokers were assigned to tasks allowing attentional freedom to look back and forth at 2 simultaneously presented pictures, whereas another 32 habitual smokers viewed single pictures without attentional choice. Picture contents in both tasks were 1 of 4 combinations: emotionally negative + neutral, negative + positive, positive + neutral, or neutral + neutral. Participants wore a nicotine patch on 1 day and placebo patch on another day. Nicotine reduced anxiety most when negative pictures were presented in combination with neutral pictures, but it had no effect on anxiety when negative pictures were presented in combination with positive pictures and when negative pictures were not presented. In contrast, nicotine only reduced depressive affect when the participant had attentional choice between positive and negative pictures. Nicotine also enhanced positive affect and reduced negative affect as measured by the Positive and Negative Affect Schedule, but these effects were not moderated by task manipulations. Overall, the findings support the view that nicotine's ability to reduce specific negative affects is moderated by emotional context and attentional freedom. Nicotine tended to enhance eye-gaze orientation to emotional pictures versus neutral pictures in women, but it had no significant effect on eye-gaze in men.

Effects of nicotine and depressive traits on affective priming of lateralized emotional word identification.

Based on evidence suggesting that depressive traits, emotional information processing, and the effects of nicotine may be mediated by lateralized brain mechanisms, analyses assessed the influence of depressive traits and nicotine patch on emotional priming of lateralized emotional word identification in 61 habitual smokers. Consistent with hypotheses, nicotine as compared to placebo patch enhanced right visual field (RVF) emotional word identification while decreasing performance of emotional word identification in the left visual field (LVF). Nicotine also enhanced positive affect and decreased negative affect. Consistent with the Heller model of depression, scoring high in depressive traits was associated with a general decrease in LVF emotional word identification. Additionally, this general LVF deficit was especially pronounced for positive word identification in individuals scoring high in trait depression. Positive primes facilitated positive target identification in the RVF and negative primes facilitated negative target identification in the LVF. Thus, nicotine promoted a LVF word-identification deficit similar to that observed in those with depressive traits. However, nicotine also enhanced RVF processing and reduced negative affect, whereas it enhanced positive affect.

Negative affect subtypes and craving differentially predict long-term cessation success among smokers achieving initial abstinence.

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.

Effects of bupropion sustained release on task-related EEG alpha activity in smokers: Individual differences in drug response.

The mechanisms underlying bupropion's efficacy as an antidepressant and a smoking cessation aid are far from being fully characterized. The present study is the first to examine the effects of bupropion on visuospatial task-related parietal EEG alpha power asymmetry-an asymmetry that has previously been found to be associated with severity of depressive symptoms (i.e., the more depressive symptoms, the greater alpha power in the right vs. left parietal area [Henriques & Davidson, 1997; Rabe, Debener, Brocke, & Beauducel, 2005]). Participants, all of whom were smokers and none of whom were clinically depressed, were randomly assigned to the Placebo group (n = 79) or Bupropion group (n = 31) in a double-blind study. EEG during the performance of the visuospatial task was collected before and after 14 days on placebo or bupropion sustained-release capsules. Relative to the Placebo group, the Bupropion group (especially, the Bupropion subgroup who had a positive right versus left parietal alpha power asymmetry at pretreatment) had a reduction in the parietal alpha asymmetry (driven largely by a decrease in right parietal alpha power). These findings support the hypothesis that bupropion can induce changes in parietal EEG asymmetry that have been shown in previous literature to be associated with a reduction in depressive states and traits. (PsycINFO Database Record

Moderation of nicotine effects on covert orienting of attention tasks by poor placebo performance and cue validity.

INTRODUCTION AND RATIONALE: Given baseline-dependent effects of nicotine on other forms of attention, there is reason to believe that inconsistent findings for the effects of nicotine on attentional orienting may be partly due to individual differences in baseline (abstinence state) functioning. Individuals with low baseline attention may benefit more from nicotine replacement. METHOD: The effects of nicotine as a function of baseline performance (bottom, middle, and top third of mean reaction times during placebo) were assessed in 52 habitual abstinent smokers (26 females/26 males) utilizing an arrow-cued covert orienting of attention task. RESULTS: Compared to a placebo patch, a 14mg nicotine patch produced faster overall reaction times (RTs). In addition, individuals with slower RTs during the placebo condition benefitted more from nicotine on cued trials than did those who had shorter (faster) RTs during placebo. Nicotine also enhanced the validity effect (shorter RTs to validly vs. invalidly cued targets), but this nicotine benefit did not differ as a function of overall placebo-baseline performance. CONCLUSIONS: These findings support the view that nicotine enhances cued spatial attentional orienting in individuals who have slower RTs during placebo (nicotine-free) conditions; however, baseline-dependent effects may not generalize to all aspects of spatial attention. These findings are consistent with findings indicating that nicotine's effects vary as a function of task parameters rather than simple RT speeding or cognitive enhancement.

Mood disturbance fails to resolve across 31 days of cigarette abstinence in women.

Smoking abstinence responses were characterized in 96 female smokers. Participants completed subjective state measures twice per week for 5 weeks and were then randomly assigned to a group required to abstain for 31 days or a control group that continued to smoke. Financial incentives for biochemically verified abstinence resulted in an 81% completion rate. Abstinence-related increases in depression, tension, anger, irritability, and appetite showed little tendency to return to prequit levels and remained significantly elevated above smoke-group levels. In contrast to psychological components of anxiety, physical components decreased to smoke group levels by the 2nd week of abstinence. Trait depression and neuroticism predicted larger increased abstinence-associated negative affect. The Big Five personality dimensions predicted variance not associated with depressive traits.

Effects of nicotine on emotional distraction of attentional orienting: evidence of possible moderation by dopamine type 2 receptor genotype.

INTRODUCTION: Growing evidence suggests that attentional bias to, and distraction by, emotional stimuli may moderate affective states and motivation for nicotine and other drug use. METHODS: The present study assessed the effects of nicotine and dopamine receptor genotype on distraction by emotional pictures, during a modified spatial attention task, in 46 overnight-deprived smokers. RESULTS: Relative to placebo, 14mg nicotine patch produced shorter overall reaction times (RTs) and individuals with two dopamine type 2 receptor (DRD2) A2 alleles exhibited the greatest RT benefit from nicotine following emotionally negative pictures after the longest cue-target delay (800ms), but benefitted least from nicotine following positive pictures after the shortest delay (400ms). In contrast, at the shortest delay, A1 carriers did not benefit from nicotine following emotionally negative pictures but did following positive ones. CONCLUSIONS: These genetic differences in the effects of nicotine on attention immediately following emotionally positive versus negative stimuli may reflect differential excitatory and inhibitory transmitter processes related to approach (reward) and avoidance (punishment) sensitivities of dopamine-related neural networks that support positive and negative affect.

Neurotransmission-related genetic polymorphisms, negative affectivity traits, and gender predict tobacco abstinence symptoms across 44 days with and without nicotine patch.

Genetic and personality trait moderators of tobacco abstinence-symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms and personality traits related to negative affect (NA). Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with 1 or 2 short alleles of 5-HTTLPR (S carriers) experienced larger increases in NA symptoms than did those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the 1st 2 weeks of treatment (when on the 21-mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes.

Effects of nicotine on affect are moderated by stressor proximity and frequency, positive alternatives, and smoker status.

The Situation x 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.

Nicotine decreases attentional bias to negative-affect-related Stroop words among smokers.

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.

Brain indices of nicotine's effects on attentional bias to smoking and emotional pictures and to task-relevant targets.

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.