Effects of nicotine on brain responses to emotional pictures.

Given that nicotine reduces negative affect, one would expect nicotine to have different effects on brain responses to emotionally negative stimuli than it does on responses to emotionally neutral or positive stimuli. However, no studies have assessed this possibility. The present study assessed the effects of nicotine patch versus placebo patch on brain event-related potential (ERP) responses to emotion-inducing negative, positive, and neutral color pictures in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included four experimental sessions. After overnight smoking deprivation (12 hr or more), active nicotine patches were applied to participants during one of the first two sessions and during one of the last two sessions. Placebo patches were applied during the other two sessions. Nicotine reduced frontal ERP processing voltage negativity (from 144-488 ms poststimulus onset) evoked by viewing emotionally negative pictures to a greater extent than it did when emotionally neutral pictures were viewed, whereas it had no effect on processing negativity evoked by positive pictures. Nicotine also enhanced P390 amplitudes evoked by emotionally negative pictures more than it did when emotionally neutral and positive pictures were viewed. Across picture types, nicotine (relative to placebo) reduced N300 amplitude (more at anterior and dorsal sites) and increased P390 amplitude. Overall, nicotine influenced ERPs to emotionally neutral and positive pictures less than it did to negative pictures.     

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.     

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.     

Treating smokers before the quit date: can nicotine patches and denicotinized cigarettes reduce cravings?

The present study investigated whether treatment with the combination of denicotinized cigarettes and 21-mg nicotine patch for 2 weeks before a designated quit date could lessen cravings for smoking, thereby helping smokers abstain from smoking. The study was a randomized controlled clinical trial conducted at Roswell Park Cancer Institute, Buffalo, New York, in 2004 and 2005. Patients included 98 adult heavy smokers (using 20 or more cigarettes/day). Half of the subjects received 2 weeks of combination of denicotinized cigarettes (Quest 3) and 21-mg nicotine patch for 2 weeks before the quit date. The remaining smokers were switched to light cigarettes (Quest 1) during the 2 weeks before the quit date. After the quit date, all subjects received counseling for smoking cessation and were provided nicotine patches for up to 8 weeks after the quit date. Self-reported cravings for smoking, withdrawal symptoms, and smoking abstinence were measured at predetermined intervals using phone-based surveys and in clinical visits. The group that used denicotinized cigarettes and nicotine patch before quitting reported less frequent and less intense cravings for cigarettes in the 2 weeks before and after the designated quit date. Self-reported withdrawal symptoms and quit rates did not differ significantly between the groups. The use of a denicotinized cigarette combined with the nicotine patch appears to lessen cravings to smoke in the immediate postcessation period. A larger, better-powered study is needed to test if this treatment combination has merit for increasing quit rates.     

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.     

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.     

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.     

Adolescent smoking trajectories and nicotine dependence.

The present study correlates empirically constructed prospective adolescent smoking trajectories with indicators of nicotine dependence assessed in adolescence and in adulthood. Excluding individuals who reported no smoking during repeat assessment (nonadopters), we identified five smoking trajectory groups: experimenters (n=116, 48.5%), late increasers (n=39, 16.3%), early increasers (n=37, 15.5%), quitters (n=22, 9.2%), and persistent smokers (n=25, 10.5%). Higher frequency of nicotine dependence symptoms in adolescence occurred in the quitters and persistent smokers groups, who smoked at higher levels relative to the experimenters, late increasers, and early increasers groups, who reported a similar frequency of nicotine dependence symptoms and smoked at low levels. Lifetime nicotine dependence was assessed in adulthood in lifetime daily smokers using the Fagerstr?m Test for Nicotine Dependence (FTND) and the Nicotine Dependence Scale (NDS). Lifetime FTND levels were similar across trajectory groups. Relative to experimenters, all remaining smoking trajectory groups had higher NDS levels that were similar to one another. These results suggest that higher levels of adolescent nicotine dependence were associated with heavier smoking trajectory groups, and that regardless of trajectory group membership, smoking more than a few cigarettes per week throughout adolescence resulted in similar levels of lifetime nicotine dependence as measured by the FTND and NDS.     

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.     

Acceptance of nicotine dependence treatment among currently depressed smokers.

This study reports on baseline characteristics associated with acceptance and refusal of available smoking treatment among currently depressed smokers in a psychiatric outpatient clinic who were enrolled in a larger clinical trial. The sample (N=154) was 68% female and 72% White, with a mean age of 41.4 years and average smoking rate of 17 cigarettes/day. All participants were assigned to a repeated contact experimental condition; received a stage-based expert system program to facilitate treatment acceptance; and were then offered smoking treatment, consisting of behavioral counseling, nicotine patch, and bupropion. Acceptors (n=53) were defined as those accepting behavioral counseling and pharmacological treatment at some point during the 18-month study, whereas refusers (n=101) received only the expert system. The number of days to treatment acceptance was significantly predicted by stage of change, with those in preparation entering treatment more quickly than contemplators or precontemplators. In a logistic regression, the variables most strongly associated with accepting treatment were current use of psychiatric medication and perceived success for quitting. Severity of depressive symptoms, duration of depression history, and history of recurrent depression were not related to treatment acceptance. Findings have implications for the psychiatric assessment and treatment of smokers in clinical settings. Psychiatric medication may play a significant role in smoking cessation treatment acceptance by currently depressed smokers.     

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 relationship between cigarette use, nicotine dependence, and craving in laboratory volunteers.

Data from epidemiological studies suggest that individual differences in cigarettes per day (CPD) and duration of smoking account for only a small portion of the variance in Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) nicotine dependence. However, DSM-IV may be an insensitive measure of nicotine dependence; other measures might better reflect the true nature of the relationship between use and dependence. This paper describes the relationship between cigarettes per day (CPD) and years smoking and the severity of nicotine dependence as measured by the Nicotine Dependence Syndrome Scale (NDSS). Furthermore, we assessed the validity of individual differences in nicotine dependence by determining whether they related to cue-evoked craving during abstinence. Data were pooled from five laboratory studies of 489 regular (i.e., 15+ CPD) smokers. In contrast to previously reported data demonstrating a relatively strong relationship between CPD and dependence in chippers (Shiffman & Sayette, 2005), CPD and years smoking accounted for a statistically significant, but small (<6%), portion of the variance in nicotine dependence in daily smokers. Individual differences in both CPD and years smoking had little or no relationship with craving. However, the magnitude of craving was significantly related to the degree of nicotine dependence even after controlling for use variables and excluding craving-related items on the NDSS. These data suggest that among moderate to heavy daily smokers, meaningful individual differences in nicotine dependence are observed independent of differences in current daily cigarette consumption and duration of smoking. Further research into the sources of this variance is critical to understanding the process of and risk for nicotine dependence.     

Factor structure and validity of the Medication Adherence Questionnaire (MAQ) with cigarette smokers trying to quit.

The Medication Adherence Questionnaire (MAQ) is a scale used to evaluate adherence to medications. The present study assessed the factor structure and validity of the MAQ with cigarette smokers. A principal components analysis was conducted on MAQ scores from a sample of smokers presenting for treatment in a clinical trial of naltrexone and nicotine patch for smoking cessation (N = 385). Indices of convergent and predictive validity were tested using electronic medication caps for naltrexone, nicotine patch counts, plasma drug levels of naltrexone, and treatment outcomes. The principal components analysis revealed two factors. Factor 1, labeled "unintentional nonadherence," measured the extent to which individuals were nonadherent because they were careless or forgot to take their medications. Factor 2, labeled "purposeful nonadherence," assessed nonadherence related to purposefully stopping medication use after feeling better or worse. Only the second factor was shown to have good convergent and predictive validity. Specifically, this factor was related to pill-taking behavior measured with electronic medication caps and drug plasma levels and nicotine patch use based on nicotine patch count data, and it was associated with smoking cessation outcome. Thus the purposeful nonadherence factor of the MAQ may be used as a brief screening tool for medication adherence with cigarette smokers seeking treatment. Information obtained with this questionnaire could be used to counsel patients regarding the importance of medication adherence.     

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.     

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).     

Effect of nicotine on 35% CO2-induced anxiety: A study in healthy volunteers.

Panic disorder and cigarette smoking co-occur at a rate that exceeds what would be expected by chance. Theoretically, cigarette smoking may (a) attenuate panicky symptoms via cognitive factors or pharmacological action, (b) contribute to the development of panic disorder, or (c) share an etiological vulnerability with panic. The present study was aimed at testing whether nicotine has a direct influence on laboratory-elicited panic. In a placebo-controlled, double-blind, randomized, cross-over study, 33 healthy nonsmokers underwent a 35% CO2 challenge after transdermal administration of a nicotine patch on one test day and a placebo patch on another test day. Physiological measures (blood pressure, heart rate) and rating scale scores (Panic Symptom List [PSL], Visual Analog Scale of Anxiety, State-Trait Anxiety Inventory) were assessed. Compared with the placebo condition, nicotine increased diastolic blood pressure (p < .1), heart rate (p < .001), and PSL scores (p < .005) prior to the CO2 challenge but did not affect responding to the CO2 challenge itself. Results are consistent with the notion that nicotine promotes autonomic activation. However, the present study did not provide direct evidence that nicotine elicits panic in healthy volunteers. Replication in a clinical sample is warranted.     

Nicotine, cotinine, withdrawal, and craving patterns during smoking and nicotine nasal spray use: results from a pilot study with African American men.

Nicotine intake via smoking is highly variable. Individualized dosing of nicotine replacement therapy (NRT) may improve product efficacy, but a better understanding of the within-day and within-subject relationships between smoking, NRT use, nicotine and cotinine concentrations in blood, and cravings and withdrawal symptoms is needed to inform dosing algorithms. A pilot study was undertaken to collect data on these relationships and to assess the feasibility of the methods needed for this type of research, including a sophisticated statistical modeling technique (a two-part mixed-effects model with correlated random effects that accounts for clumping at zero). Because nicotine metabolism varies by gender and race, the sample was homogeneous with respect to these characteristics. In a within-subjects study, 27 African American adult male smokers carried a computerized cigarette dispenser for 1 week, capturing the time each cigarette was smoked. Subjects then entered an inpatient setting for 1 day of scheduled smoking (matched to data from the cigarette dispenser to create an ecologically valid schedule) and 4 days of ad libitum nicotine nasal spray use, while tobacco abstinent. Eight times per day, at 2-hour intervals, blood was drawn and ratings of cigarette cravings and withdrawal symptoms were obtained. On average, subjects used less than half of the manufacturer's recommended minimum daily dose of nicotine nasal spray. Large differences in nicotine and cotinine levels were observed between individuals. When predicting nicotine, cotinine, withdrawal, and cravings, we observed significant interactions between route of nicotine intake and a variety of independent variables.     

The serotonin transporter 5-HTTLPR polymorphism and treatment response to nicotine patch: follow-up of a randomized controlled trial.

In this follow-up of a randomized placebo-controlled clinical trial of nicotine replacement transdermal patch for smoking cessation, 741 smokers of European ancestry who were randomized to receive active patch or placebo patch were genotyped for the serotonin transporter gene-linked polymorphic region. The study setting was a primary care research network in Oxfordshire, United Kingdom. The primary outcome measures were biochemically verified sustained abstinence from cigarette smoking at end of treatment and 24-week follow-up. The main effect of genotype was not associated with sustained abstinence from smoking at either end of treatment (SL: p=.33; SS: p=.81) or 24-week follow-up (SL: p=.05; SS: p=.21), and we found no evidence for a genotypextreatment interaction effect. In summary, despite the theoretically important contribution of serotonin neurotransmission to smoking cessation, the serotonin transporter gene was not associated with treatment response to nicotine patch for smoking cessation in this primary care-based trial.     

Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences.

This double-blinded, placebo-controlled trial evaluated the efficacy of naltrexone as an adjunct to standard smoking cessation treatment. Participants (N = 110) were adult male and female nicotine-dependent smokers who expressed interest in quitting smoking. All subjects received six sessions of behavioral counseling (1 hr/session for 6 weeks), and 1 month of the nicotine patch (21 mg for the first 2 weeks, 14 mg the third week, 7 mg the fourth week). Subjects were randomly assigned to the naltrexone or placebo group. The naltrexone group started at 25 mg daily for 3 days prior to the quit date, and increased to 50 mg/day on the quit date and following 8 weeks. At the end of medication treatment, the naltrexone group had better quit rates versus the placebo group (48% quit on naltrexone vs. 41% on placebo), but this difference was not statistically significant. However, men and women differed on several measures: in the placebo group, women had significantly lower quit rates than men (39% vs. 67%, p<.05), but in the naltrexone group, women had quit rates comparable with those of men (58% vs. 62%, p = ns). Further examination revealed that naltrexone significantly reduced men's and women's cessation-related weight gain and selectively reduced women's urge to smoke to relieve negative affect and withdrawal. The results suggest continued examination of naltrexone as an adjunct in smoking cessation, particularly in female smokers, who have historically shown worse outcomes with traditional treatment methods.     

A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation

A randomized double-blind, active controlled, parallel group, multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment (under Investigational Device Exemption 69,185). The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking. Treatment consisted of Quest brand of cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59+/-0.06, 0.3+/-0.05, and less than 0.05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of continuous abstinence (Weeks 7-10), with additional follow-up at 3 and 6 months. Adult men and women smokers (N = 346), motivated to quit, were randomized to one of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and NRT after the quit date), Quest plus placebo patch, or active control plus NRT (conventional cigarette, followed by NRT after quit date). Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT (16.4% vs. 21.9%). No serious adverse events were attributable to the investigational product. Quest plus NRT offers promise as a new smoking cessation treatment.