Nicotine encourages oxidative stress and impairment of rats' brain mitigated by Spirulina platensis lipopolysaccharides and low-dose ionizing radiation.

Nicotine is a psychoactive alkaloid of tobacco, which is ingested during cigarettes or electronic cigarette smoking. Extensive consumption of nicotine induced oxidative stress. Accordingly, it is implicated in many pathophysiology brain disorders and triggers neurodegeneration. In this study, we investigated the protective role of Spirulina platensis-lipopolysaccharides (S.LPS) and the low dose-ionizing radiation (LD-IR) against the induced neurotoxicity in the rats' brain due to the prolonged administration of high nicotine levels. Rats treated with nicotine for two months showed alterations in the oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG)), antioxidant enzymes (superoxide dismutase (SOD), catalase (Cat), glutathione enzymes (GPx and GST)) as well as several pro-inflammatory markers (Tumor Necrosis Factor-alpha (TNF-α), Interleukin-17 (IL-17), and Nuclear Factor-kappa B (NF-κB)), and induced apoptosis through Caspase-3 activity. Nicotine also upregulated the mRNA gene expression of cytochrome P450 enzymes (CYP2B1 and CYP2E1), Cyclin-dependent kinase 5 (CDK5), Toll-Like Receptor 4 (TLR4), and phospho-Tau (p-Tau) protein expression. Besides, it downregulated the alpha-7 nicotinic receptor (α7nAChR) mRNA gene expression accompanied by a decline in the calcium (Ca2+) level. S.LPS exhibited antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective activities, which counteracting the detrimental effects of chronic nicotine administration. LD-IR demonstrated comparable effects to S.LPS. Exposure of rats to LD-IR enhanced the neuroprotective effects of S.LPS against nicotine toxicity. The light microscopic examination of the brain tissues was in agreement with the biochemical investigations. These findings display that S.LPS and LD-IR mitigated the oxidative stress and the impairment of rats' brain induced by nicotine, due to regulation of the mRNA gene expression of cytochrome P450 enzymes (CYP2B1 and CYP2E1) and the signaling pathway of Tau protein phosphorylation.

Nicotine Use Disorders in Adolescents.

Rates of certain tobacco products have decreased over the past decade, but nicotine use disorder is still prevalent among adolescents. New trends in tobacco use, such as in the use of electronic cigarettes, are creating alarm. This article reviews nicotine addiction and measurement in adolescents, along with potential health risks and comorbidities. Various psychosocial and pharmacologic interventions are reviewed along with novel interventions that show promise for reducing tobacco use in this vulnerable population.

Nicotine impairs intra-substance tendon healing after full thickness injury in a rat model.

Nicotine is harmful to many bodily systems; however, the effects of nicotine on intra-substance tendon healing remain largely unexplored. The purpose of this study was to examine the functional, structural, and biomechanical effects of nicotine on the healing of Achilles tendons in rats after an acute full-thickness injury. Sixty Sprague-Dawley rats were enrolled in this study. Half were exposed to 0.9% saline and half to 61 ng/mL of nicotine for 3 months via subcutaneous osmotic pumps. At 3 months, all rats underwent blunt full thickness transection of the left Achilles tendon and were immobilized for one week in plantarflexion. In-vivo assays were conducted prior to injury, at 21 days, and at 42 days post-injury and included the following: Functional limb assessment, passive joint mechanics, and vascular evaluation. Rats were sacrificed at 21 and 42 days for biomechanical testing and histologic evaluation. Rats exposed to nicotine demonstrated decreased vascularity, greater alteration in gait mechanics, and increased passive ROM of the ankle joint. Biomechanically, the nicotine tendons failed at lower maximum loads, were less stiff, had smaller cross-sectional areas and had altered viscoelastic properties. Histologically, nicotine tendons demonstrated decreased vessel density at the injury site. This study demonstrates that nicotine leads to worse functional outcomes and biomechanical properties in tendons. The decreased vascularity in the nicotine group may suggest an underlying mechanism for inferior tendon healing. Patients should be counseled that using nicotine products increase their risk of poor tendon healing and may predispose them to tendon re-rupture. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats.

We tested the hypothesis that nicotine exposure in utero and after birth [developmental nicotine exposure (DNE)] disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brain stem slices from 1- to 5-day-old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine (ACh) receptors with nicotine (i.e., an acute nicotine challenge). Under baseline conditions, there were no significant effects of DNE on the amplitude or frequency of either sIPSCs or mIPSCs. In addition, DNE did not alter the magnitude of the whole cell current evoked by bath application of glycine, consistent with an absence of change in postsynaptic glycine-mediated conductance. An acute nicotine challenge (bath application of 0.5 µM nicotine) increased sIPSC frequency in the DNE cells, but not control cells. In contrast, nicotine challenge did not change mIPSC frequency in either control or DNE cells. In addition, there were no significant changes in the amplitude of either sIPSCs or mIPSCs in response to nicotine challenge. The increased frequency of sIPSCs in response to an acute nicotine challenge in DNE cells reflects an enhancement of action potential-mediated input from glycinergic interneurons to hypoglossal motoneurons. This could lead to more intense inhibition of hypoglossal motoneurons in response to exogenous nicotine or endogenous ACh. The former would occur with smoking or e-cigarette use while the latter occurs with changes in sleep state and with hypercapnia. NEW & NOTEWORTHY Here we show that perinatal nicotine exposure does not impact baseline glycinergic neurotransmission to hypoglossal motoneurons but enhances glycinergic inputs to hypoglossal motoneurons in response to activation of nicotinic acetylcholine (ACh) receptors with acute nicotine. Given that ACh is the endogenous ligand for nicotinic ACh receptors, the latter reveals a potential mechanism whereby perinatal nicotine exposure alters motor function under conditions where ACh release increases, such as the transition from non-rapid-eye movement to rapid-eye movement sleep, and during hypercapnia.

The Effect of Electronic Cigarettes on Hand Microcirculation.

PURPOSE: Smoking conventional cigarettes reduces peripheral microcirculation leading to worse outcomes after hand surgery. Patients are increasingly using electronic cigarettes (eCigarettes); however, there is no published research investigating the effects of eCigarettes on hand microcirculation. METHODS: Fifteen healthy subjects with a median age of 26 years were recruited: 7 smokers and 8 nonsmokers. A noninvasive O2C laser Doppler probe measured a baseline control reading at deep (7-mm) and superficial (3-mm) levels. Participants commenced a 5-minute smoking protocol of nonnicotine (0-mg) eCigarettes with continuous microcirculation measurements during smoking and for 20 minutes afterward. This was repeated with nicotine (24-mg) eCigarettes. Readings were averaged over 5-minute periods and standardized as a percentage of baseline. A linear mixed-effects model with an unstructured covariance structure was used to analyze the data. RESULTS: Smokers had a statistically significant reduction in hand microcirculation during and up to 20 minutes after smoking a 24-mg eCigarette. There was a maximum reduction of 77% in superficial flow and 29% in deep flow. After smoking a 0-mg eCigarette, smokers demonstrated an increase in superficial flow of up to 70% with no change in deep flow. Nonsmokers had no statistically significant change in superficial or deep flow after smoking either eCigarette. CONCLUSIONS: A 24-mg eCigarette significantly reduced smokers' hand microcirculation during and after smoking. Microcirculation increased in smokers after inhalation of a 0-mg eCigarette. CLINICAL RELEVANCE: We advise smokers undergoing hand surgery to avoid high-dose eCigarettes and, if necessary, to use 0-mg eCigarettes as an alternative.

Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents.

BACKGROUND: Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans. METHODS AND RESULTS: Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures. CONCLUSIONS: The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure.

Commonly used stimulants: Sleep problems, dependence and psychological distress.

BACKGROUND: Caffeine and nicotine are commonly used stimulants that enhance alertness and mood. Discontinuation of both stimulants is associated with withdrawal symptoms including sleep and mood disturbances, which may differ in males and females. The present study examines changes in sleep quality, daytime sleepiness and psychological distress associated with use and dependence on caffeine and nicotine. METHODS: An online survey comprising validated tools to assess sleep quality, excessive daytime sleepiness and psychological distress was completed by 166 participants (74 males, 96 females) with a mean age of 28 years. Participants completed the study in their own time, and were not offered any inducements to participate. RESULTS: Sleep quality was poorer in those dependent upon caffeine or nicotine, and there were also significant interaction effects with gender whereby females reported poorer sleep despite males reporting higher use of both stimulants. Caffeine dependence was associated with poorer sleep quality, increased daytime dysfunction, and increased levels of night time disturbance, while nicotine dependence was associated with poorer sleep quality and increased use of sleep medication and sleep disturbances. There were strong links between poor sleep and diminished affect, with psychological distress found to co-occur in the context of disturbed sleep. CONCLUSIONS: Stimulants are widely used to promote vigilance and mood; however, dependence on commonly used drugs including caffeine and nicotine is associated with decrements in sleep quality and increased psychological distress, which may be compounded in female dependent users.

Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates.

OBJECTIVE: We previously demonstrated that prenatal nicotine exposure decreases neonatal pulmonary function in nonhuman primates, and maternal vitamin C supplementation attenuates these deleterious effects. However, the effect of nicotine on placental perfusion and development is not fully understood. This study utilizes noninvasive imaging techniques and histological analysis in a nonhuman primate model to test the hypothesis that prenatal nicotine exposure adversely effects placental hemodynamics and development but is ameliorated by vitamin C. STUDY DESIGN: Time-mated macaques (n = 27) were divided into 4 treatment groups: control (n = 5), nicotine only (n = 4), vitamin C only (n = 9), and nicotine plus vitamin C (n = 9). Nicotine animals received 2 mg/kg per day of nicotine bitartrate (approximately 0.7 mg/kg per day free nicotine levels in pregnant human smokers) from days 26 to 160 (term, 168 days). Vitamin C groups received ascorbic acid at 50, 100, or 250 mg/kg per day with or without nicotine. All underwent placental dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at 135-140 days and Doppler ultrasound at 155 days to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. Animals were delivered by cesarean delivery at 160 days. A novel DCE-MRI protocol was utilized to calculate placental perfusion from maternal spiral arteries. Placental tissue was processed for histopathology. RESULTS: Placental volume blood flow was significantly reduced in nicotine-only animals compared with controls and nicotine plus vitamin C groups (P = .03). Maternal placental blood flow was not different between experimental groups by DCE-MRI, ranging from 0.75 to 1.94 mL/mL per minute (P = .93). Placental histology showed increased numbers of villous cytotrophoblast cell islands (P < .05) and increased syncytiotrophoblast sprouting (P < .001) in nicotine-only animals, which was mitigated by vitamin C. CONCLUSION: Prenatal nicotine exposure significantly decreased fetal blood supply via reduced placental volume blood flow, which corresponded with placental histological findings previously associated with cigarette smoking. Vitamin C supplementation mitigated the harmful effects of prenatal nicotine exposure on placental hemodynamics and development, suggesting that its use may limit some of the adverse effects associated with smoking during pregnancy.

Smoking and plastic surgery, part I. Pathophysiological aspects: update and proposed recommendations.

OBJECTIVES: Smoking patients undergoing a plastic surgery intervention are exposed to increased risk of perioperative and postoperative complications. It seemed useful to us to establish an update about the negative impact of smoking, especially on wound healing, and also about the indisputable benefits of quitting. We wish to propose a minimum time lapse of withdrawal in the preoperative and postoperative period in order to reduce the risks and maximize the results of the intervention. METHODS: A literature review of documents from 1972 to 2014 was carried out by searching five different databases (Medline, PubMed Central, Cochrane library, Pascal and Web of Science). RESULTS: Cigarette smoke has a diffuse and multifactorial impact in the body. Hypoxia, tissue ischemia and immune disorders induced by tobacco consumption cause alterations of the healing process. Some of these effects are reversible by quitting. Data from the literature recommend a preoperative smoking cessation period lasting between 3 and 8 weeks and up until 4 weeks postoperatively. Use of nicotine replacement therapies doubles the abstinence rate in the short term. When a patient is heavily dependent, the surgeon should be helped by a tobacco specialist. CONCLUSIONS: Total smoking cessation of 4 weeks preoperatively and lasting until primary healing of the operative site (2 weeks) appears to optimize surgical conditions without heightening anesthetic risk. Tobacco withdrawal assistance, both human and drug-based, is highly recommended.

The effect of TENS on random pattern flap survival in nicotinized rats.

The adverse effects of cigarettes, due to their nicotine content, may cause important ischemic complications in flaps. Electrical stimulation increases blood flow in ischemic tissues, the level of vascular endothelial growth factor, capillary density, and angiogenesis while decreasing oxygen tension in tissues. Electrical stimulation is also known to increase survival rate in flaps. In this study, which tests the hypothesis that TENS (a type of electrical stimulation) contributes to enhancement of flap viability by eliminating the adverse effects of nicotine, 40 rats were divided into 4 groups of 10 rats. Nicotinization was achieved by subcutaneous administration of 2 mg/kg per day to the rats, other than those in the Control group, for 4 weeks. The rats in one of the nicotinized groups received 20 mA, 80 Hz TENS (TENS1 group) for 1 hour daily throughout the last week before McFarlane flaps of random pattern were made in the backs of all the rats. Another nicotinized group was subjected to TENS in a similar dose after flap elevation (TENS2 group). Flap blood flow was measured before and 48 hours after their construction, and their fluorescein perfusion was measured immediately after the flap elevation. The comparison of the survival rates of the flaps revealed that, although the blood flow in the Nicotine group was significantly lower than in the Control group, it was significantly higher in the TENS1 group than in both the Control and Nicotine groups. The proportion of the area stained with fluorescein, immediately after the elevation of flaps, was significantly reduced in the Nicotine group compared to the Control group. In the TENS1 group, however, it was greater than in the nicotine and TENS2 groups. Flap viability rates decreased significantly in the Nicotine group compared with the Control group. In the TENS2 group, however, an increase was observed compared with the Nicotine group.These findings suggest that although TENS performed before flap elevation does not contribute to flap survival, despite causing a rise in blood flow, it enhances flap survival when applied postoperatively. Given the practicality and low cost of TENS, it can be concluded that it may be possible to use it in the management of ischemic complications in flap operations in smokers.

Snus (Swedish smokeless tobacco) use and risk of stroke: pooled analyses of incidence and survival.

BACKGROUND: Snus is a moist smokeless tobacco product with high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear. OBJECTIVE: The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes. METHODS: Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively. RESULTS: No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) amongst users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61). CONCLUSION: Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared with nonusers, but further studies are needed to determine any possible causal mechanisms.

Trait differences in response to chronic nicotine and nicotine withdrawal in rats.

INTRODUCTION: Understanding an individual's vulnerability to drug addiction has important implications for the development of effective personal treatment plans. Although theories acknowledge impulsive behaviour as a key component of drug addiction, little is known about the influence of trait impulsivity on an individual's susceptibility to the effects of psychostimulants on impulsivity at critical phases of the addiction cycle. METHODS: This study investigated the short and longer-term effects of chronic nicotine administration on impulsive choice in rats selected for high (HI) and low impulsivity (LI) on a delay discounting task. Rats prepared with subcutaneously osmotic mini-pumps received either nicotine (3.16 mg/kg/day [freebase]) or saline for 7 days. Performance was assessed during chronic treatment, early and late withdrawal, and in response to acute nicotine challenges following prolonged abstinence. RESULTS: Chronic nicotine increased impulsive choice in LI but not HI animals. Spontaneous withdrawal was associated with a nicotine abstinence syndrome, the early stages of which were characterised by opposing effects on impulsive choice in HI and LI animals. A transient decrease in impulsivity was observed in HI animals whilst the LI group remained more impulsive for up to 1 week following drug termination. Following normalisation of behaviour, acute nicotine challenges (0.125, 0.25, 0.5 mg/kg, SC) markedly increased impulsive choice regardless of trait impulsivity and drug history. CONCLUSION: The results indicate that only LI individuals are vulnerable to chronic drug- and withdrawal-induced impairments in self-control which may increase the likelihood of the transition to, and maintenance of, nicotine dependence.

Handling relapse in smoking cessation: strategies and recommendations.

Once established, smoking is a very difficult addiction to break. Many smokers persist in tobacco use for several years and typically cycle through multiple periods of remission and relapse. Smoking cessation is not a single event but a process, and relapse is an ordinary component of this process. While international guidelines place great emphasis on relapse prevention, very little can be found about managing smokers who have relapsed. This article is intended to address the challenge of managing smokers who relapse in the course of a smoking cessation program. This knowledge may lead to an improved smoking cessation outcomes.

The effect of hyperbaric oxygen treatment on the healing of burn wounds in nicotinized and nonnicotinized rats.

The importance of oxygen in wound healing and the negative effects of cigarette smoking have been demonstrated in various studies. In this study, our aim was to investigate the effect of hyperbaric oxygen (HBO2) treatment on wound healing in nicotinized and nonnicotinized rats. The study was conducted on 32 Sprague Dawley rats. The rats were divided into four groups, with eight rats in each: group 1, nonnicotinized rats; group 2, nonnicotinized rats treated with HBO2; group 3, nicotinized rats; and group 4, nicotinized rats treated with HBO2. To prepare the nicotinized groups, the rats were given nicotine for 28 days. At the end of day 28, standard, deep, second-degree to third-degree burns were created on the rats. The HBO2-treated groups underwent HBO2 treatment once a day for 7 days after the creation of the burn damage. All rats were killed 21 days after injury, and the burns were subjected to macroscopic, histopathological, and microbiological evaluation. During this evaluation, the smallest necrotic areas and the lowest rate of fibrosis were observed in group 2. The largest necrotic areas and the highest inflammation and fibrosis rates were observed in the nicotine-treated group 3. When the nicotinized and nonnicotinized groups were compared separately, there was a significant difference in favor of the groups treated with HBO2. Bacterial growth was the highest in the nicotinized group 3, whereas no statistically significant difference was observed among the other groups. We conclude that HBO treatment accelerates the recovery of burn wounds and provides more effective healing by reducing the development of scars both in nicotinized and nonnicotinized rats.

Short- and long-term consequences of nicotine exposure during adolescence for prefrontal cortex neuronal network function.

More than 70% of adolescents report to have smoked a cigarette at least once. At the adolescent stage the brain has not completed its maturation. The prefrontal cortex (PFC), the brain area responsible for executive functions and attention performance, is one of the last brain areas to mature and is still developing during adolescence. Smoking during adolescence increases the risk of developing psychiatric disorders and cognitive impairment in later life. In addition, adolescent smokers suffer from attention deficits, which aggravate with the years of smoking. Recent studies in rodents reveal the molecular changes induced by adolescent nicotine exposure that alter the functioning of synapses in the PFC and that underlie the lasting effects on cognitive function. Here we provide an overview of these recent findings.

Effect of nicotine on growth and metabolism of Streptococcus mutans.

Streptococcus mutans is a key contributor to dental caries. Smokers have a higher number of caries-affected teeth than do nonsmokers, but the association among tobacco, nicotine, caries, and S. mutans growth has not been investigated in detail. Seven S. mutans strains--UA159, UA130, 10449, A32-2, NG8, LM7, and OMZ175--were used in the present study. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), planktonic cell growth, biofilm formation, metabolism, and structure (determined using scanning electron microscopy) of the seven strains treated with different concentrations of nicotine (0-32 mg ml(-1)) were investigated. The MIC, MBC, and MBIC were 16 mg ml(-1) (0.1 M), 32 mg ml(-1) (0.2 M), and 16 mg ml(-1) (0.1 M), respectively, for most of the S. mutans strains. Growth of planktonic S. mutans cells was significantly repressed by 2.0-8.0 mg ml(-1) of nicotine. Biofilm formation and metabolic activity of S. mutans was increased in a nicotine-dependent manner up to 16.0 mg ml(-1) of nicotine. Scanning electron microscopy revealed that S. mutans treated with a high concentration of nicotine a had thicker biofilm and more spherical bacterial cells. In summary, nicotine enhances S. mutans biofilm formation and biofilm metabolic activity. These results suggest that smoking can increase the development of caries by fostering increased formation of S. mutans biofilm on tooth surfaces.

Prenatal exposure to cigarette smoke or alcohol and cerebellum volume in attention-deficit/hyperactivity disorder and typical development.

Prenatal exposure to teratogenic substances, such as nicotine or alcohol, increases the risk of developing attention-deficit/hyperactivity disorder (ADHD). To date, studies examining this relationship have used symptom scales as outcome measures to assess the effect of prenatal exposure, and have not investigated the neurobiological pathways involved. This study explores the effect of prenatal exposure to cigarettes or alcohol on brain volume in children with ADHD and typically developing controls. Children with ADHD who had been exposed prenatally to either substance were individually matched to children with and without ADHD who had not been. Controls who had been exposed prenatally were also individually matched to controls who had not been. For prenatal exposure to both smoking and alcohol, we found a pattern where subjects with ADHD who had been exposed had the smallest brain volumes and unexposed controls had the largest, with intermediate volumes for unexposed subjects with ADHD. This effect was most pronounced for cerebellum. A similar reduction fell short of significance for controls who had been exposed to cigarettes, but not alcohol. Our results are consistent with an additive effect of prenatal exposure and ADHD on brain volume, with the effects most pronounced for cerebellum.

Predictors of risk for smoking relapse in men and women: a prospective examination.

The current study examined whether prequit trait negative mood and smoking motives have different predictive patterns of smoking relapse in men and women. Thirty-three female (mean age±SEM: 34.9±2.5) and 38 male (mean age±SEM: 37.1±2.3) smokers interested in smoking cessation completed forms on smoking history, negative mood (i.e., depression, anxiety, and anger), stress, and smoking motives. Participants also provided samples for measurement of cotinine and carbon monoxide. Then, they set a quit date and were required to abstain from smoking at least for 24 hours. Participants were followed up for 12 months postcessation to measure their smoking status. Cox proportional hazard models revealed that motivation to reduce craving was a unique predictor of smoking relapse in men, while depressive mood, anxiety, anger, and perceived stress were predictive of time to relapse among women. These findings remained significant after statistically controlling for smoking-related variables, providing preliminary evidence that different factors may be associated with nicotine withdrawal and smoking relapse in men and women.