Endothelial-derived extracellular vesicles associated with electronic cigarette use impair cerebral microvascular cell function.

The aim of this study was to determine the effect of circulating endothelial cell-derived microvesicles (EMVs) isolated from e-cigarette users on human cerebral microvascular endothelial cells (hCMECs) nitric oxide (NO) and endothelin (ET)-1 production and tissue-type plasminogen activator (t-PA) release. Circulating EMVs (CD144-PE) were isolated (flow cytometry) from 27 young adults (19-25 yr): 10 nonsmokers (6 M/4 F), 10 e-cigarette users (6 M/4 F), and 7 tobacco cigarette smokers (4 M/3 F). hCMECs were cultured and treated with isolated EMVs for 24 h. EMVs from e-cigarette users and cigarette smokers induced significantly higher expression of p-eNOS (Thr495; 28.4 ± 4.6 vs. 29.1 ± 2.8 vs. 22.9 ± 3.8 AU), Big ET-1 (138.8 ± 19.0 vs. 141.7 ± 19.1 vs. 90.3 ± 18.8 AU) and endothelin converting enzyme (107.6 ± 10.1 and 113.5 ± 11.8 vs. 86.5 ± 13.2 AU), and significantly lower expression of p-eNOS (Ser1177; 7.4 ± 1.7 vs. 6.5 ± 0.5 vs. 9.7 ± 1.6 AU) in hCMECs than EMVs from nonsmokers. NO production was significantly lower and ET-1 production was significantly higher in hCMECs treated with EMVs from e-cigarette (5.7 ± 0.8 µmol/L; 33.1 ± 2.9 pg/mL) and cigarette smokers (6.3 ± 0.7 µmol/L; 32.1 ± 3.9 pg/mL) than EMVs from nonsmokers (7.6 ± 1.2 µmol/L; 27.9 ± 3.1 pg/mL). t-PA release in response to thrombin was significantly lower in hCMECs treated with EMVs from e-cigarette users (from 38.8 ± 6.3 to 37.4 ± 8.3 pg/mL) and cigarette smokers (31.5 ± 5.5 to 34.6 ± 8.4 pg/mL) than EMVs from nonsmokers (38.9 ± 4.3 to 48.4 ± 7.9 pg/mL). There were no significant differences in NO, ET-1, or t-PA protein expression or production in hCMECs treated with EMVs from e-cigarette users and smokers. Circulating EMVs associated with e-cigarette use adversely affects brain microvascular endothelial cells and may contribute to reported cerebrovascular dysfunction with e-cigarette use.NEW & NOTEWORTHY In the present study, we determined the effect of circulating endothelial cell-derived microvesicles (EMVs) isolated from e-cigarette users on human cerebral microvascular endothelial cells (hCMECs) nitric oxide (NO) and endothelin (ET)-1 production and tissue-type plasminogen activator (t-PA) release. EMVs from e-cigarette users reduced brain microvascular endothelial cell NO production, enhanced ET-1 production, and impaired endothelial t-PA release. EMVs are a potential mediating factor in the increased risk of stroke associated with e-cigarette use.

Feasibility of Using an Armband Optical Heart Rate Sensor in Naturalistic Environment.

Consumer-grade heart rate (HR) sensors including chest straps, wrist-worn watches and rings have become very popular in recent years for tracking individual physiological state, training for sports and even measuring stress levels and emotional changes. While the majority of these consumer sensors are not medical devices, they can still offer insights for consumers and researchers if used correctly taking into account their limitations. Multiple previous studies have been done using a large variety of consumer sensors including Polar® devices, Apple® watches, and Fitbit® wrist bands. The vast majority of prior studies have been done in laboratory settings where collecting data is relatively straightforward. However, using consumer sensors in naturalistic settings that present significant challenges, including noise artefacts and missing data, has not been as extensively investigated. Additionally, the majority of prior studies focused on wrist-worn optical HR sensors. Arm-worn sensors have not been extensively investigated either. In the present study, we validate HR measurements obtained with an arm-worn optical sensor (Polar OH1) against those obtained with a chest-strap electrical sensor (Polar H10) from 16 participants over a 2-week study period in naturalistic settings. We also investigated the impact of physical activity measured with 3-D accelerometers embedded in the H10 chest strap and OH1 armband sensors on the agreement between the two sensors. Overall, we find that the arm-worn optical Polar OH1 sensor provides a good estimate of HR (Pearson r = 0.90, p <0.01). Filtering the signal that corresponds to physical activity further improves the HR estimates but only slightly (Pearson r = 0.91, p <0.01). Based on these preliminary findings, we conclude that the arm-worn Polar OH1 sensor provides usable HR measurements in daily living conditions, with some caveats discussed in the paper.

Effect of restricting menthol flavored cigarettes or E-cigarettes on smoking behavior in menthol smokers.

Bans of menthol characterizing flavor in tobacco products have been enacted in some localities and proposed in the United States for cigarettes. To gather data regarding how restrictions for menthol in cigarettes and e-cigarettes may affect current menthol cigarette smokers, 37 African American menthol smokers participated in a pilot study in which they were asked to abstain (n = 18) or not abstain from menthol cigarettes (n = 19) for 8-weeks. All participants received menthol flavored e-cigarettes for 4 weeks and tobacco flavored e-cigarettes for 4 weeks in random order. Number of cigarettes smoked per day (estimated mean ratio [EMR] = 0.31; 95% CI: 0.13, 0.72) and exhaled CO concentrations (EMR = 0.61; 95% CI: 0.43, 0.88) were lower in the menthol cigarette abstainer group compared to the menthol cigarette non-abstainer group. Those in the menthol cigarette abstainer group reported higher scores on motivation to quit (p = 0.03) and perceived effectiveness of quitting skills (p = 0.02). There were no substantial effects seen in amount smoked or exhaled CO based on flavor of e-cigarettes provided. Higher e-cigarette use (based on reported puffs per day) was reported in the menthol cigarette abstainer (vs. non-abstainer) group (p < 0.01) and also during the 4-week period when provided with menthol (vs. tobacco) e-cigarettes (p < 0.01). These data suggest that the potential of e-cigarettes to reduce tobacco related harm may be enhanced if combined with a ban on menthol flavor in combustible cigarettes. Larger studies are needed to determine the effect of limiting menthol in e-cigarettes on smoking behavior among current menthol smokers.

Effect on Tobacco Use and Subjective Measures of Including E-cigarettes in a Simulated Ban of Menthol in Combustible Cigarettes.

INTRODUCTION: Bans of menthol characterizing flavor in tobacco products have been proposed; however, there is limited data regarding the impact on current menthol cigarette smokers of including e-cigarettes in such bans. METHODS: In this six-week pilot study, 47 menthol smokers were randomized to receive all tobacco products from an experimental marketplace simulating either no menthol ban, a menthol ban for cigarettes but not e-cigarettes, or a ban for both ("total menthol ban"). RESULTS: At the first visit, all but one participant selected cigarettes with e-cigarettes selected by 38%, 69%, and 40% of participants in the no ban, menthol cigarette ban, and total menthol ban groups, respectively. Over the study period, the total menthol ban group smoked more than the menthol cigarette ban group (estimated mean ratio [EMR] in cigarettes per day = 1.38; 95% CI: 1.1, 1.75; p = .006). Compared to the no ban condition, the menthol cigarette ban group smoked slightly fewer (EMR = 0.87; 95% CI: .68, 1.11) and the total menthol ban group smoked slightly more (EMR = 1.20; 95% CI: 1.00, 1.45) although neither difference reached statistical significance. In both menthol ban conditions, ratings were lower (vs. no ban) on several measures of craving and cigarette effects and liking. CONCLUSIONS: Menthol bans that include e-cigarettes may result in different patterns of tobacco use than if only combustible cigarettes are included, although e-cigarettes were not extensively used in any group. Larger studies are needed to determine policies most likely to provide the largest public health benefit. IMPLICATIONS: Bans of menthol characterizing flavor have been proposed, however, the effects on menthol cigarette smokers of including e-cigarettes in such bans are not clear. This study found that smokers randomized to a simulated ban on menthol in both cigarettes and e-cigarettes smoked more cigarettes per day over the 6-week study period than those randomized to a simulated ban on menthol in only cigarettes suggesting that smoking patterns among current menthol smokers differ depending on which products are included in a menthol ban. Larger studies are needed to determine the policies most likely to provide the largest public health benefit.

Knowledge, Attitudes, and Beliefs about Relapse Prevention Research Involving Bupropion among Current and Former Pregnant Individuals Who Smoke.

Introduction: While many individuals quit smoking during pregnancy, most relapse within one year postpartum. Research into methods to decrease smoking relapse postpartum has been hampered by difficulties with recruitment. Method: We conducted individual interviews with pregnant women (N = 22) who were interested in quitting smoking while pregnant about their attitudes regarding smoking and quitting during pregnancy, clinical trial participation, and smoking cessation medication use. Results: Participants were aware of the risks of smoking while pregnant. Many wanted to quit smoking before delivery. Few used empirically supported treatments to quit. While research was viewed positively, interest in taking on new commitments postpartum and taking a medication to prevent relapse was low. Medication concerns were evident among most participants, especially among those planning to breastfeed. Further, several women noted medication was unnecessary, as they did not believe they would relapse postpartum. Financial incentives, childcare, and fewer and/or remote visits were identified as facilitators to participating in research. However, these factors did not outweigh women's concerns about medication use and time commitments. Conclusions: Women are aware that quitting smoking during pregnancy and remaining smoke-free postpartum are important. However, beliefs that personal relapse risk is low and that medications are dangerous reduced enthusiasm for taking medication for postpartum relapse prevention. Future medication trials should educate women about the high likelihood of relapse, prepare to answer detailed questions about risks of cessation medications, and connect with participants' clinicians. For new mothers, studies conducted remotely with few scheduled appointments would reduce barriers to participation.

Effects on Smoking Behavior of Switching Menthol Smokers to Non-menthol Cigarettes.

INTRODUCTION: Bans of menthol characterizing flavor in cigarettes have been implemented in some localities and have been proposed more broadly. One proposed benefit of such a ban is to increase cessation rates among current menthol smokers. There is currently relatively limited data regarding how smoking behavior changes if menthol smokers switch to non-menthol cigarettes. AIMS AND METHODS: African American menthol smokers interested in quitting smoking were randomized to either continue smoking menthol (n = 60) or switch to non-menthol cigarettes (n = 62) for 1 month prior to a cessation attempt. Cessation results were reported previously; this analysis reports the results from the pre-cessation visits at which amount smoked, exhaled carbon monoxide (CO) concentration, urinary cotinine concentrations, and subjective measures were assessed. RESULTS: Over the 4-week study period, those switching to non-menthol (vs. continuing to smoke menthol) cigarettes smoked fewer cigarettes per day (mean ratio: 0.86; 95% confidence interval [CI]: 0.76, 0.98; p = .02), reported lower withdrawal symptom severity (mean difference -1.29; 95% CI: -2.6 to -0.01; p = .05) and higher perceived effectiveness of their skills for quitting smoking (mean difference 0.56; 95% CI: 0.02-1.10; p = .05). No significant differences were found between groups in exhaled CO, urinary cotinine concentrations, or most other subjective effects including support for a ban on menthol characterizing flavor in cigarettes. CONCLUSIONS: These results suggest that were menthol cigarettes no longer available, those that switch to non-menthol cigarettes would not change their smoking behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefit.Clinicaltrials.gov # NCT02342327. IMPLICATIONS: A ban on menthol characterizing flavor in cigarettes has been proposed as a potential means by which to increase smoking cessation rates among current menthol cigarette smokers. This study evaluated how African American menthol cigarette smokers adjusted their smoking behavior after switching to non-menthol cigarettes. Although the overall differences between groups were modest, they were in a direction consistent with decreased smoking suggesting that current smokers would not adjust their behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefits.

Effects on time to lapse of switching menthol smokers to non-menthol cigarettes prior to a cessation attempt: a pilot study.

INTRODUCTION: Menthol smokers (particularly African-Americans) have lower cessation success rates than non-menthol smokers. With bans being considered on characterising menthol flavour in cigarettes, data are needed regarding how switching to non-menthol cigarettes impacts cessation measures. METHODS: In this randomised pilot study, African-American menthol cigarette smokers interested in quitting smoking either continued smoking menthol cigarettes (n=60) or switched to non-menthol cigarettes (n=62) for a 1-month period prior to a cessation attempt. The primary endpoint was time to smoking lapse (ie, time from quitting until any smoking). Additional endpoints included time to smoking relapse (ie, number of days from quitting until the first of seven consecutive smoking days) and difference between groups in subjective measures. RESULTS: After attempting to quit, the non-menthol cigarette group had indications of delayed time to lapse (HR 0.82; 95% CI 0.55 to 1.22; p=0.33) and time to relapse (HR 0.67; 95% CI 0.42 to 1.06; p=0.09), although these were not statistically significant. Post hoc analyses suggest that observed differences were largely due to a smaller proportion of participants in the non-menthol group relapsing within the first day of quitting (21% vs 40%; p=0.05). Values of other measures assessed postcessation were largely similar between groups. CONCLUSIONS: These data suggest that among African-American smokers, a menthol cigarette ban would not undermine short-term cessation measures and may result in some benefits. Future research is needed to assess longer term cessation rates and to identify interventions to maximise cessation success in the event of a menthol ban. TRIAL REGISTRATION NUMBER: NCT02342327.

Using consumer-wearable technology for remote assessment of physiological response to stress in the naturalistic environment.

Psychosocial stress is a major risk factor for morbidity and mortality related to a wide range of health conditions and has a significant negative impact on public health. Quantifying exposure to stress in the naturalistic environment can help to better understand its health effects and identify strategies for timely intervention. The objective of the current project was to develop and test the infrastructure and methods necessary for using wearable technology to quantify individual response to stressful situations and to determine if popular and accessible fitness trackers such as Fitbit® equipped with an optical heart rate (HR) monitor could be used to detect physiological response to psychosocial stress in everyday life. The participants in this study were University of Minnesota students (n = 18) that owned a Fitbit® tracker and had at least one upcoming examination. Continuous HR and activity measurements were obtained during a 7-day observation period containing examinations self-reported by the participants. Participants responded to six ecological momentary assessment surveys per day (~ 2 hour intervals) to indicate occurrence of stressful events. We compared HR during stressful events (e.g., exams) to baseline HR during periods indicated as non-stressful using mixed effects modeling. Our results show that HR was elevated by 8.9 beats per minute during exams and by 3.2 beats per minute during non-exam stressors. These results are consistent with prior laboratory findings and indicate that consumer wearable fitness trackers could serve as a valuable source of information on exposure to psychosocial stressors encountered in the naturalistic environment.

Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.

BACKGROUND: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. METHODS: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis. RESULTS: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. CONCLUSIONS: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. IMPACT: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease.

Effect of nicotine lozenge use prior to smoking cue presentation on craving and withdrawal symptom severity.

BACKGROUND: Smokers are often advised to use nicotine lozenge after cravings or withdrawal symptoms are present, which may be too late to prevent lapses. This study assesses if lozenge use prior to smoking cue exposure attenuates cue-induced increases in symptom severity. METHODS: In this randomized, cross-over study, participants completed three laboratory sessions at which they proceeded through 4 "rooms" in a virtual reality environment. The first and last "rooms" contained neutral cues and the others contained smoking cues. At one session, a 4 mg nicotine lozenge was not given until after cue exposure (to approximate current use: i.e., after craving and withdrawal symptoms occur). At the other two sessions either a nicotine or placebo lozenge was used 15 min before cue exposure procedures. Craving and withdrawal symptoms were measured throughout each laboratory session. RESULTS: Of 58 participants randomized; 40 completed all 3 labs. Absolute levels of craving and withdrawal symptom severity during cue exposure were lower when placebo or active lozenge was used prior to cue presentation procedures vs. no treatment until after cue presentation procedures (all p-values <0.05). There were no differences among conditions in the magnitude of symptom severity increase occurring between the first neutral room and the cue rooms. CONCLUSIONS: Lozenge use prior to cue exposure may minimize cue induced symptom severity but when taken 15 min prior to cues the decrease is not different than placebo. Research is needed to determine if another time-frame relative to cue exposure would be more effective.

Effects of Very Low Nicotine Content Cigarettes on Smoking Behavior and Biomarkers of Exposure in Menthol and Non-menthol Smokers.

INTRODUCTION: Because 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy. METHODS: In a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence. RESULTS: At baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (-6.4 vs. -9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (-4.5 vs. -7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition. CONCLUSIONS: Although menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers. IMPLICATIONS: Results of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes.

Effects of smoking and paroxetine on stress-induced craving and withdrawal symptoms.

BACKGROUND: When smokers relapse, many cite stressful circumstances as the cause. Most smoking cessation medications do not prevent stress induced increases in craving and withdrawal symptom severity; however the effect of smoking prior to stress exposure on symptom severity is unclear. METHODS: We examined how smoking a cigarette immediately prior to a stressful task affects craving and withdrawal symptom severity by analyzing data from a double-blind, crossover study assessing paroxetine's effects on the physiological response to the combination of stress and smoking. Measures were obtained prior to and following smoking / stress exposure and following a subsequent 30 minute period at two laboratory sessions (i.e., after one month each of paroxetine and placebo). RESULTS: Among study completers (n=63), severity of craving decreased from the beginning of the session to immediately following the smoking / stress exposure (p<0.01) and severity of smoking urges decreased from the beginning to the end of the laboratory session (p<0.001). Withdrawal symptoms were less severe while taking paroxetine vs. placebo (p<0.05) but no treatment x time effects were observed. CONCLUSIONS: Additional research is needed to identify interventions that could similarly decrease stress induced craving in order to determine if smoking cessation rates can be increased.

Sex differences in physiological response to the combination of stress and smoking.

Stressful situations are among the most commonly cited smoking triggers. Smoking and stress exposure each individually increase cardiovascular and hypothalamic-pituitary-adrenal measures with larger increases occurring when stress and smoking are combined. In this analysis, sex differences in the physiological response to the combination of stress and smoking are examined. Smokers (36 males; 34 females) completed a laboratory session in which systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), plasma epinephrine (Epi), norepinephrine and cortisol concentrations were measured at rest, while smoking a cigarette, during a speech task occurring immediately after smoking and at several time-points following the stressor. Significant period by sex effects were observed for HR, SBP, DBP and Epi but not for cortisol or norepinephrine concentrations. For SBP (p=0.002), the increase between resting and speech were larger in men than in women, primarily due to a larger increase between smoking and speech occurring in men. A similar pattern was observed for DBP and Epi with a significantly larger Epi increase from smoking to speech observed in men than in women (p=0.016). A different pattern emerged for HR - the total increase was larger in women (p<0.001), due to a larger rest to smoking increase (p<0.001). In most measures therefore, overall increases were greater in men than women, primarily due to larger smoking to speech increases. Additional research is needed to determine the clinical implications of these results as they apply to sex difference in smoking cessation success rates and in the cardiovascular risks of smoking.

Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

INTRODUCTION: Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. METHODS: Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). RESULTS: Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (p<0.03) and for factor 1 of the QSU when lozenge was used 10min prior to the stressor (p=0.028). Absolute levels of post-stressor withdrawal symptom and urge to smoke severity were lower when lozenge was given prior to versus after a stressor. CONCLUSIONS: Administering the nicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963.

Use of an automated mobile application to assess effects of nicotine withdrawal on verbal fluency: A pilot study.

Mild-to-moderate impairment in frontally mediated functions such as sustained attention, working memory, and inhibition have been found to occur during tobacco withdrawal and may present a barrier to successful cessation. These findings have led to studies evaluating cessation treatments that target nicotine withdrawal related cognitive impairment. The instruments currently used to assess cognitive function provide detailed and specific information but have limitations including being time consuming, cumbersome, anxiety provoking, and having poor ecological validity. The authors examined the feasibility of using a mobile computer application to test verbal fluency (VF) as a quick, easy-to-administer, and more ecologically valid method of measuring the effects of short-term smoking abstinence on frontally mediated cognitive functions. Thirty participants completed 2 assessments-1 during ad lib smoking and 1 after overnight abstinence. At each assessment, semantic and phonemic VF tests were administered using a mobile application and nicotine craving and withdrawal symptom severity was assessed. In repeated assessments, performance on both semantic and phonemic VF tests is expected to improve due to practice effects; however, significant improvements were observed only in semantic (p = .012) but not phonemic (p = .154) VF. In addition, the change between assessments in phonemic (but not semantic) score was significantly associated with withdrawal (p = .006) and craving (p = .037) severity measured postabstinence. This study demonstrates that nicotine withdrawal has differential effects on semantic versus phonemic VF suggesting impairments of working memory, attention, and inhibition. These effects were measured using methods easily used in large groups of participants, potentially with remote test administration and automated scoring. (PsycINFO Database Record

Effect of paroxetine on physiological response to stress and smoking.

OBJECTIVE: Smokers often smoke during stressful events, which leads to large increases in cardiovascular measures such as blood pressure (BP) and heart rate (HR). Because exaggerated cardiovascular response to stress is associated with cardiovascular disease risk, this study examined paroxetine's effect on the physiological response to combining stress and smoking. METHODS: Sixty-two participants completed this randomized, double-blind, crossover study in which BP, HR, plasma epinephrine, norepinephrine, and cortisol concentrations were measured at rest, while smoking, and during a speech and math task. Laboratory sessions occurred after 1 month of paroxetine and after 1 month of placebo. RESULTS: Significant increases occurred for all measures (except cortisol) during smoking, with further increases occurring during the speech task (time effect, p < .001). After 1 month of paroxetine, norepinephrine and HR values were lower and cortisol values were higher (versus placebo) throughout the laboratory session (treatment effect, p < .001). Treatment × time effects were observed for BP and HR (all, p < .01). For systolic and diastolic BP, a smaller increase (from baseline to measures during speech) was observed after paroxetine compared with placebo (both, p < .006). In both measures, the increase in response to smoking was similar for both treatments; however, the further increase during the speech was smaller when taking paroxetine (versus placebo). CONCLUSIONS: This study suggests that paroxetine affects physiological response to stress in smokers. Further research is needed to determine the impact of these results on cardiovascular health. Trial Registration clinicaltrials.gov Identifier: NCT00218439.

Menstrual phase and depressive symptoms differences in physiological response to nicotine following acute smoking abstinence.

INTRODUCTION: Accumulating evidence has linked depressive symptoms and sex hormones to risk for relapse; however, the specific mechanisms involved in these associations remain unknown. This randomized crossover study assessed physiological response to nicotine by menstrual phase in female smokers with and without depressive symptoms following acute smoking abstinence. METHODS: Females, ages 18-40 years with regular menstrual cycles, not on exogenous hormones or psychotropic medications, who reported smoking ≥ 5 cigarettes/day were enrolled. Participants were stratified into 2 groups: no depressive symptoms (NDS; n = 23) and depressive symptoms (DS; n = 24). After 4 days of biochemically verified smoking abstinence, participants completed 2 laboratory sessions in the follicular (F) and luteal (L) phases. Participants used nicotine nasal spray at Time 0, and blood pressure, heart rate, and serum nicotine were measured at Time -1, 5, 10, 20, 30, 45, 60, and 90 min. RESULTS: Participants (n = 47) were 29.1 ± 6.8 years old and smoked an average of 12.5 ± 5.1 cigarettes/day. The NDS group had more pronounced menstrual phase differences (F > L) in diastolic blood pressure, heart rate, and maximum concentrations of nicotine compared with the DS group (p < .05). CONCLUSIONS: This study observed an interaction between sex hormones and depressive symptoms such that those without depressive symptoms had a greater menstrual phase difference in the physiological response to nicotine. These data offer additional support for the role of sex hormones in the physiological response to nicotine, which may play a role in menstrual phase effects on smoking cessation.

Effect of stress and bupropion on craving, withdrawal symptoms, and mood in smokers.

INTRODUCTION: Studies suggest that in smokers attempting to quit smoking, the occurrence of stressful events is associated with smoking relapse. The purpose of this study was to determine the effect of bupropion (an agent known to increase smoking cessation rates) on the craving, withdrawal, and mood response to stressful tasks administered in a laboratory setting. METHODS: Response to three tasks (a speech, math, and cold pressor task) was measured in 65 smokers during ad libitum smoking. Smokers were then randomized to either bupropion or placebo. Fourteen days after starting medication, 43 subjects (28 receiving bupropion and 15 receiving placebo) quit smoking and laboratory procedures were repeated on the third day of abstinence. RESULTS: Prior to cessation, stressors presented in a laboratory setting increased craving, nicotine withdrawal symptoms, and subjective distress but decreased positive affect. Thirty minutes of relaxation after the stressors did not result in these measures returning to prestress levels. During the nicotine withdrawal period, stress-induced responses were generally smaller than during the precessation period. Bupropion (relative to placebo) reduced overall levels of craving and withdrawal symptoms but did not have significant effects on response to stress during the nicotine withdrawal period. CONCLUSIONS: This study demonstrates that stress results in sustained increases in craving and withdrawal symptoms and changes in mood symptoms and that bupropion affects overall levels of these symptoms. Further research is needed to determine if modifying response to stress is predictive of an effective treatment for facilitating smoking cessation.

Effect of oral snus and medicinal nicotine in smokers on toxicant exposure and withdrawal symptoms: a feasibility study.

BACKGROUND: Smokeless, spitless tobacco products are being introduced and marketed as cigarette substitutes. Data are needed regarding how smokers interested in cessation would use these products, the levels of resultant toxicant exposure, and the feasibility of using these products as aids for tobacco cessation. METHODS: Smokers were randomized to receive Camel Snus (n = 51), Taboka (n = 52), or medicinal nicotine (n = 27) and required to quit smoking for 4 weeks. Measures of toxicant exposure and symptoms of craving and withdrawal were assessed prior to and during product use. RESULTS: Concentrations of exhaled carbon monoxide, urinary cotinine, urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and urinary N'-nitrosonornicotine and its glucuronide (total NNN) were significantly (P values <0.05) lower at the end of treatment in each group except for total NNN in those receiving Camel Snus (P = 0.066). A significant group × time effect was observed for total NNAL concentrations (P = 0.002) with the decrease greatest in the medicinal nicotine group and smallest decrease in the Camel Snus group. No significant differences between groups were found in craving and withdrawal symptoms. CONCLUSIONS: Enrolling smokers into a cessation study utilizing newer smokeless tobacco products is feasible. Camel Snus and Taboka use was not found to be superior to medicinal nicotine in reducing withdrawal symptoms but decreases in NNAL were smaller in users of Camel Snus. IMPACT: This study demonstrates the feasibility of conducting a smoking cessation study utilizing these newer tobacco products. An appropriately powered study is needed to assess smoking cessation rates using these newer products compared with established, safer products such as medicinal nicotine.

Reduced nicotine content cigarettes: effects on toxicant exposure, dependence and cessation.

AIMS: To examine the effects of reduced nicotine cigarettes on smoking behavior, toxicant exposure, dependence and abstinence. DESIGN: Randomized, parallel arm, semi-blinded study. Setting University of Minnesota Tobacco Use Research Center. INTERVENTIONS: Six weeks of: (i) 0.05 mg nicotine yield cigarettes; (ii) 0.3 mg nicotine yield cigarettes; or (iii) 4 mg nicotine lozenge; 6 weeks of follow-up. Measurements Compensatory smoking behavior, biomarkers of exposure, tobacco dependence, tobacco withdrawal and abstinence rate. FINDINGS: Unlike the 0.3 mg cigarettes, 0.05 mg cigarettes were not associated with compensatory smoking behaviors. Furthermore, the 0.05 mg cigarettes and nicotine lozenge were associated with reduced carcinogen exposure, nicotine dependence and product withdrawal scores. The 0.05 mg cigarette was associated with greater relief of withdrawal from usual brand cigarettes than the nicotine lozenge. The 0.05 mg cigarette led to a significantly higher rate of cessation than the 0.3 mg cigarette and a similar rate as nicotine lozenge. CONCLUSION: The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.