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.     

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.     

The effects of smoking deprivation and nicotine administration on emotional reactivity.

Although converging lines of evidence suggest that nicotine and mood are related at a fundamental biological level, this link has not been reliably demonstrated in laboratory studies. In this study, startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes associated with motivation. Smokers (N = 115) completed four laboratory sessions crossing deprivation (12-hr deprived vs. nondeprived) with nicotine spray (active vs. placebo). Participants viewed affective pictures (positive, negative, neutral) and pictures involving cigarette cues, while startle probes were administered. Deprivation decreased startle responding to cigarette cues, suggesting an activation of appetitive processes. Nicotine administration suppressed overall startle responding during deprivation. In addition, during deprivation, random exposure to negative stimuli over two blocks of trials resulted in decreased adaptation of the startle response, suggesting that some sensitization to negative emotional cues may take place during nicotine withdrawal. These effects are consistent with formulations of addiction, stressing that withdrawal may both increase the reinforcement salience of smoking stimuli and decrease habituation to negative emotional stimuli.     

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.     

Rate of nicotine onset from nicotine replacement therapy and acute responses in smokers.

The subjective and reinforcing effects of drugs of abuse may depend partly on their rate of onset, with faster acting formulations typically producing stronger effects than slower ones. In this within-subjects study, we examined the acute effects of nicotine replacement therapy via nicotine nasal spray (fast delivery) vs. transdermal nicotine patch (slow delivery) on craving, withdrawal, cardiovascular responses, subjective ratings, and reinforcing effects of smoking. Smokers (N=30) not seeking treatment participated in three sessions, each after overnight smoking abstinence, involving 14-mg nicotine (Nicoderm) or placebo patch, followed 4 hr later by intermittent administration of nicotine (Nicotrol) or placebo nasal spray. Specifically, the three group comparisons were nicotine patch condition (with placebo spray), nicotine spray condition (with placebo patch), and placebo condition (placebo spray and patch). Nicotine patch and nicotine spray were never administered in the same session. Blood nicotine levels were similar between nicotine patch and nicotine spray conditions, by design. Heart rate and systolic blood pressure were higher following nicotine spray vs. the other conditions, as hypothesized. However, other than reductions in craving related to nicotine spray and patch at some points, no differences between conditions were observed in withdrawal, subjective effects of sprays and smoking, or smoking reinforcement assessed by a computer task. Thus, under these acute conditions, the speed of nicotine delivery from nasal spray vs. patch differentially affected cardiovascular responses and perhaps craving but did not influence withdrawal, subjective ratings, and smoking reinforcement.     

The reinforcing effects of nicotine and stimulant medication in the everyday lives of adult smokers with ADHD: A preliminary examination.

Whereas the smoking prevalence rates in the general population are declining, rates among people diagnosed with attention-deficit/hyperactivity disorder (ADHD) continue to be elevated. Previous research has shown that nicotine may improve attention and mood, suggesting that nicotine may help ameliorate the attentional and emotional problems associated with ADHD. The present study examined the effects of nicotine with and without stimulant medication on ADHD symptoms, moods, and arousal in the everyday lives of smokers with ADHD. A total of 10 smokers with ADHD who were being treated with stimulant medication were asked to abstain from smoking while participating in the study. Participants underwent four conditions in randomized order: (a) Nicotine patch+stimulant medication, (b) nicotine patch only, (c) placebo patch+stimulant medication, and (d) placebo patch only. Each condition continued for 2 days, during which self-reports of ADHD symptoms and moods were obtained using electronic diaries. Lightweight ambulatory monitors recorded cardiovascular activity at each diary entry. Smoking abstinence was verified by expired carbon monoxide and salivary cotinine analysis. Results showed that nicotine patches and stimulant medication alone and in combination reduced difficulty concentrating and core ADHD symptoms compared with placebo patch only. Borderline improvement in impatience and self-control was seen with nicotine patch administration primarily on day 1. Nicotine patches also tended to elevate systolic and diastolic blood pressure compared with placebo patch during day 2. The findings suggest that smokers with ADHD experience nicotine-related reductions in ADHD symptoms during their everyday lives.     

Dopamine receptor (DRD2) genotype-dependent effects of nicotine on attention and distraction during rapid visual information processing.

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).     

Acute nicotine fails to alter event-related potential or behavioral performance indices of auditory distraction in cigarette smokers.

Behavioral studies have shown that nicotine enhances performance in sustained attention tasks, but they have not shown convincing support for the effects of nicotine on tasks requiring selective attention or attentional control under conditions of distraction. We investigated distractibility in 14 smokers (7 females) with event-related brain potentials (ERPs) and behavioral performance measures extracted from an auditory discrimination task requiring a choice reaction time response to short- and long-duration tones, both with and without embedded deviants. Nicotine gum (4 mg), administered in a randomized, double-blind, placebo-controlled crossover design, failed to counter deviant-elicited behavioral distraction (i.e., slower reaction times and increased response errors), and it did not influence the distracter-elicited mismatch negativity, the P300a, or the reorienting negativity ERP components reflecting acoustic change detection, involuntary attentional switching, and attentional reorienting, respectively. Results are discussed in relation to a stimulus-filter model of smoking and in relation to future research directions.     

A psychometric evaluation of cigarette stimuli used in a cue reactivity study.

Laboratory studies have demonstrated that cigarette smokers react with significant subjective and autonomic responses (e.g., increased craving and increased heart rate) in the presence of stimuli associated with smoking. Although cue reactivity effects are typically robust, a number of methodological considerations make interpretation and design of cue reactivity studies problematic. Previous research has paid scant attention to the psychometric properties of the cigarette cues presented, and standard cues would enhance comparison and synthesis of studies. In the present study, we evaluated 12 cigarette photos (compared with positive, negative, and neutral photos), used in a separate study, for their ability to evoke self-report of craving in both nicotine-deprived and nondeprived smokers. These photos performed as expected, with cigarette pictures evoking significantly higher craving than neutral pictures and deprived smokers showing a trend toward higher craving than nondeprived smokers. The cigarette picture set was evaluated for internal consistency (Cronbach's alpha = .97) as a 12-item scale and further reduced to multiple 2-item scales with reliability estimates ranging from .70 to .93. A cluster analysis of all pictures showed that, when rated for craving, cigarette pictures clustered together, indicating they had distinct properties compared with positive, negative, and neutral pictures. Effect sizes were calculated for each cigarette picture in both deprived and nondeprived smokers. The craving effect sizes ranged from .57 to .98 for nondeprived smokers, and from .61 to .99 for deprived smokers. The analyses suggest these cigarette pictures have excellent psychometric properties for use in future cue reactivity studies.     

Comparison of the effects of a 24-hour nicotine patch and a 16-hour nicotine patch on smoking urges and sleep.

This randomized, open-label, crossover study was conducted to compare the effects of a 24-hr nicotine patch and a 16-hr nicotine patch on morning smoking urges and sleep quality of dependent smokers during a short period of cigarette abstinence. A total of 20 smokers (9 women and 11 men) smoking at least 20 cigarettes/day completed the two smoke-free study periods. For each period, cigarette abstinence started on the first evening and a nicotine patch was applied the next morning (for 16 or 24 hr), after baseline measures; a second patch was applied the next morning, 1 hr before the end of the experimental period. Smoking urges, mood and behavior self-reports, psychomotor performance, and polysomnographic recordings were compared between the two types of nicotine patch according to changes from baseline. Both patches decreased morning smoking urges, although results were significantly superior for the 24-hr patch. Furthermore, the 24-hr patch was more effective than the 16-hr patch in reducing the positive reinforcing dimension of smoking urges. Regarding polysomnographic recordings, the proportion of slow wave sleep was significantly increased from baseline with the 24-hr patch compared with the 16-hr patch. As for psychomotor performance measured through the critical flicker fusion test, significant improvement in morning alertness was observed in the 24-hr patch group. In conclusion, the 24-hr nicotine patch formulation is more effective than the 16-hr formulation in alleviating morning smoking urges and more specifically the positive reinforcing factor. The present findings do not support the idea that nicotine delivery during bedtime might disturb sleep, but rather it improves restorative sleep and postwaking arousal.     

Sex differences in long-term smoking cessation rates due to nicotine patch

Compared to men, women may be at greater risk for smoking-related diseases and have greater difficulty quitting smoking. Sex differences in medication response could guide treatment for smoking cessation to improve women's quit rates. We conducted a meta-analysis of the 14 placebo-controlled nicotine patch trials (N = 6,250) for which long-term (6 months) clinical outcome results could be determined separately by sex. This analysis updated a meta-analysis of 11 of these trials that found no significant sex differences due to nicotine patch. The increase in quitting due to the nicotine vs. placebo patch was only about half as large in women as in men. Pooled absolute quit rates at 6 months for nicotine and placebo patch, respectively, were 20.1% and 10.8% in men, and 14.7% and 10.1% in women. The odds ratio for quitting due to nicotine vs. placebo patch was lower in women (OR = 1.61) than in men (OR = 2.20), with an interaction odds ratio of 1.40 (95% CI = 1.02-1.93, p = .04). This sex difference did not vary significantly by whether or not formal counseling was provided. Poorer outcomes in women vs. men treated with nicotine patch suggests that increasing the quit rates of women smokers may require supplementing patch treatment or use of other medications.     

Effect of high-dose nicotine patch therapy on tobacco withdrawal symptoms among smokeless tobacco users.

No pharmacotherapies have been shown to increase long-term (> or = 6-month) abstinence rates among smokeless tobacco (ST) users. Available evidence suggests that underdosing may occur with standard-dose nicotine replacement therapy (NRT) in ST users. We investigated the effect of high-dose nicotine therapy on tobacco withdrawal symptoms among ST users in a randomized, controlled clinical pilot study. A total of 42 ST users using at least 3 cans or pouches per week were randomized to nicotine patch doses of 63, 42, or 21 mg/day or placebo for 8 weeks. Multiple daily assessments of tobacco withdrawal and nicotine toxicity were obtained with an electronic diary. During the first week of nicotine patch therapy, we observed a dose-response relationship such that higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.87, p = .009), less negative affect (chi2 = 3.85, p = .05), and less restlessness (chi2 = 3.90, p = .048). During the second week, higher nicotine patch doses were associated with less decreased arousal (chi2 = 6.77, p = .009). Overall, the frequency of nicotine toxicity symptoms did not differ by dose group. Of specific symptoms, nausea was observed to be more frequent in the 63 mg/day dose group compared with placebo (p = .035). In conclusion, high-dose nicotine patch therapy resulted in a greater reduction of tobacco withdrawal symptoms among ST users using at least 3 cans per week. High-dose nicotine patch therapy is safe and well tolerated in this population of tobacco users.     

Nicotine patch and lozenge are effective for women.

It has been hypothesized that women may be less likely to obtain therapeutic benefit from nicotine replacement therapy (NRT). The present study tested this hypothesis, using two different types of NRT medications. A secondary analysis of two randomized clinical trials was performed: One compared active 21-mg nicotine patch with placebo among 193 men and 309 women, and the other compared active 2-mg or 4-mg nicotine lozenge with placebo among 788 men and 1,030 women. Using logistic regression analysis of 6-month continuous abstinence and survival analysis, we assessed the efficacy of patch and lozenge among women and tested for a gender x treatment interaction. Active NRT was more effective than placebo among women, for both patch and lozenge. In the lozenge trial, women were less successful than men. The gender x treatment interaction was not significant in either study, whether assessed by logistic regression or survival analysis. In the lozenge trial, gender moderated the effects of smoking rate and dependence (but not treatment) on outcome: These variables affected success rates only among women. Treatment with nicotine patch or lozenge is effective for women, and the analysis did not reveal significant gender differences in efficacy. Gender differences in outcome may be moderated by nicotine dependence.     

A red code triggers an unintended approach motivation toward sweet ultra-processed foods: Possible implications for front-of-pack labels

Front-of-package labels (FOPL) are recommended to reduce consumer intake of ultra-processed food products (UPP). The multiple traffic-light label is one example of FOPL that indicates the content of target nutrients in products by displaying red (high), amber (medium), and/or green (low) color-coding. The red code may implicitly enhance sweetness perception and approach dispositions toward sweet UPP via cross-modal visual-taste interactions. We conducted two experiments to examine the possibility of contradictory influence of explicitly learned and implicit cross-modal associations on the emotional responses evoked by UPP pictures. In both experiments, we first explicitly associated the color codes with health-related meanings. In Experiment I (n = 78), a psychometric tool estimated the emotional responses (pleasantness and arousal ratings) evoked by UPP pictures when preceded by red, amber, or green color-codes. In Experiment II (n = 24), we recorded participants’ electrocortical brain activity to assess the early posterior negativity (EPN) component as an index of the emotional responses to UPP. The reported pleasantness (Experiment I) and the EPN amplitude (Experiment II) were greater for sweet UPP relative to salty UPP when primed with red codes but not when primed with green or amber. A red code increased positive emotions toward sweet UPP despite its explicit association with increased health-risks. Thus, the use of multiple traffic-lights might lead to an unintended implicit approach behavior toward sweet UPP. Designers, researchers, and policy makers may consider color-taste cross-modal associations when designing, testing, and applying FOPL.     

The discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine as a function of light physical activity.

Smokers often experience the acute effects of cigarette smoking while they are engaged in the light physical activity of routine tasks. However, virtually all laboratory-based research on these effects is conducted under conditions of quiet rest and, thus, may not generalize to effects in the natural environment. We examined changes in the discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine in humans as a function of the level of concurrent physical activity. Men and women smokers (N = 17) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) at rest. Three sessions then followed, in which the generalization of discrimination was tested across a range of doses (0-20 microg/kg) while at rest or engaged in very light or light physical activity (15% and 30% of heart rate reserve, respectively) via bicycle ergometer. Generalization testing involved both two- and three-choice ("novel" option) quantitative procedures. Self-reported mood via the Profile of Mood States and visual analog scales, and cardiovascular measures of heart rate and blood pressure were obtained concurrent with discrimination responding. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure under the same rest or activity conditions. Results showed that physical activity did not significantly alter nicotine discrimination or reinforcement, as no interactions between activity and nicotine were observed. When activity and nicotine influenced the same subjective and cardiovascular responses, they acted in a generally additive fashion. These findings suggest that research on the acute effects of nicotine conducted under typical resting laboratory conditions generally are not altered by light physical activity and so may generalize to the effects of nicotine under conditions common in the natural environment.     

Smokers' expectancies for nicotine replacement therapy vs. cigarettes.

Smokers (N=188) recruited from the local community completed a questionnaire that measured expected outcomes of using cigarettes, nicotine gum, nicotine patch, and nicotine nasal spray. Expectancy questions relating to negative affect, craving, weight, and health risks were derived from the Smoking Consequences Questionnaire-Adult. As predicted, smokers held much greater expectancies that cigarettes help control negative affect, craving, and weight relative to nicotine replacement therapy (NRT). All NRT products were expected to cause fewer health risks than cigarette smoking. As predicted, smokers held strong negative affect reduction expectancies for cigarette smoking. For NRT, although still relatively low, craving reduction was the strongest expectancy. Individuals who had experience using the nicotine patch had greater positive expectancies for NRT. Greater positive expectancies for NRT were correlated with more immediate plans to quit smoking. In summary, cigarette smokers' positive expectancies about cigarettes do not appear to generalize to NRT products, which may limit their use and effectiveness.     

基于PLSR分析常规化学成分对市售卷烟感官品质的影响

为研究常规化学成分对市售卷烟感官品质特征的影响,采用偏最小二乘回归法(partial least square regression,PLSR)分析常规化学指标总糖、还原糖、烟碱、总氮等与卷烟感官品质的相关性。结果表明:总糖、还原糖、糖碱比与舒适感所有指标呈正相关;烟碱、总氮、钾与卷烟的舒适感特性呈负相关;钾氯比与口腔刺激/舌部灼烧和口腔残留/干燥感呈显著正相关。在卷烟的烟气特性中,总糖、还原糖、糖碱比与大部分烟气特性指标呈正相关;烟碱与丰富性呈显著负相关,与劲头呈显著正相关;钾氯比与杂气呈显著正相关。     

Instructions about nicotine dose influence acute responses to nasal spray.

Effects of substance use are typically assumed to be related to pharmacological actions. However, beliefs about the drug content of a substance may strongly influence subjective and reinforcing responses to that substance (i.e., "placebo" effects). We examined the subjective and reinforcing effects of a nasal spray containing no nicotine as a function of instructions about the nicotine content of the spray (Told Nicotine vs. Told No Nicotine). Smokers (n=49) not interested in quitting smoking abstained overnight prior to a single session in which they were randomly assigned to one of three groups, involving one of the two instructional sets or a group that got no spray. Following dose instructions, subjects in the two spray groups were administered one set of four sprays from the spray bottle and then rated them intermittently on items related to "reward" (e.g., "liking", amount they would pay for more) and other effects. At the same time points, they also rated mood, craving, and withdrawal, and had heart rate and blood pressure measured. Reinforcement was then determined by the number of ad libitum sprays they self-administered during a 20-min period. The no-spray group simply rested quietly during the session, while measures were assessed at the same time points as subjects in the other two groups. Those in the Told Nicotine group reported greater spray ratings of "how much nicotine," "liking," "satisfying," "buzz/head rush," and "similar to smoking" compared with the Told No Nicotine group. Craving decreased more for those Told Nicotine versus those Told No Nicotine, but also decreased more for those Told No Nicotine compared with the no spray group. There were no significant differences in amount they would pay for more sprays, withdrawal, mood, cardiovascular responses, or in spray self-administration. These results show that instructions about the nicotine content of a novel delivery device (nasal spray) can influence self-reported spray ratings and reduce craving but are limited with respect to effects on other measures of drug response.     

Smoking cessation in homeless populations: a pilot clinical trial.

This study, which tested two motivational interviewing treatment approaches, assessed the feasibility of conducting a community-based smoking cessation intervention among homeless smokers. Participants (N = 46) were recruited from multiple facilities in the Kansas City area and were randomized to two counseling conditions in which they received five individual motivational interviewing sessions, six group meetings, and their choice of 8 weeks of 21-mg nicotine patch or 4-mg nicotine lozenge. The two counseling conditions consisted of motivational interviewing targeted either to smoking behaviors exclusively (smoking only) or to smoking and other addictions or life events that could affect ability to quit (smoking plus). Group meetings were designed to provide educational information and social support. Measures of feasibility assessed included the proportion of participants who returned for randomization among those eligible, adherence to prescribed nicotine replacement therapies, retention rates at the week 26 final study visit, and biochemically verified 7-day abstinence at week 26. Most participants (69.6%) chose nicotine patches, and 32% of those participants reported using at least four patches per week. Carbon monoxide verified 7-day abstinence rates in the smoking-only and smoking-plus groups were 13.04% and 17.39% (ns), respectively, at week 8 and 8.70% and 17.39% (ns), respectively, at week 26. Participants who used at least four patches per week were more likely to have quit at 8 weeks than were those who used fewer patches (33.3% vs. 10.5%, p = .30). Results support the feasibility of conducting a smoking cessation intervention among homeless smokers. Findings also show promising effects for nicotine replacement therapy and counseling in this population. Developing programs to improve smoking cessation outcomes in underserved populations is an essential step toward achieving national health objectives and for ultimately reducing tobacco-related health disparities.     

Transdermal nicotine use in postmenopausal women: does the treatment efficacy differ in women using and not using hormone replacement therapy?

This study of postmenopausal female smokers (N = 94) asked: During short-term smoking abstinence, do the beneficial effects of transdermal nicotine replacement therapy (NRT) on acute symptomatology (i.e., withdrawal, cigarette craving, smoking urges, mood, depressive symptoms, motor speed, and reaction time) differ in women who use and do not use hormone replacement therapy (HRT)? Participants were recruited according to HRT and non-HRT use (self-selecting), then randomized within strata to active nicotine or placebo nicotine patch. After 1 baseline week of smoking, participants quit smoking for 2 weeks. Women received cessation counseling and were monitored for abstinence. Dependent measures were collected during five clinic visits. Two-way analysis of covariance (ANCOVA) were run on change scores for dependent variables, with nicotine patch group (active/placebo) and HRT group (HRT/non-HRT) as independent variables and age as a covariate. No interactions were found between HRT and patch condition, but both showed specific effects. During the first abstinent week, women on active nicotine patch (compared with placebo) experienced less severe withdrawal, greater reductions in cigarette cravings, and lower (more favorable) Factor 1 scores on the Questionnaire of Smoking Urges. During the second abstinent week, women using HRT (compared with the non-HRT group) exhibited better mood (Profile of Mood States scores) and less depression (Beck Depression Inventory scores). These results suggest the following: First, the efficacy of transdermal nicotine replacement is not adversely modified by women's HRT use; second, ovarian hormones might influence women's responses to smoking cessation, and thus should be considered in developing effective strategies for women to quit smoking.