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Aim: Much research has been conducted on the acute effects of nicotine on human cognitive performance, demonstrating both enhancing and impairing cognitive effects. With the relatively recent introduction of electronic cigarettes ('e-cigarettes') as a smoking cessation device, little is known about the cognitive effects of e-cigarettes specifically, either as a nicotine replacement device or in the absence of nicotine. The purpose of this review was to present an overview of evidence from empirical studies on the effect of e-cigarettes on cognitive function. Approach: Guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines (PRISMA-ScR), SCOPUS, PubMed, and EBSCOhost were searched from 2006, the year e-cigarettes were introduced, to June 2023 for relevant papers, along with reference lists checked for additional papers. Key findings: Seven experimental and four cross-sectional survey studies were identified and included. The majority of the studies only include regular and current cigarette smokers and primarily assessed the acute cognitive effect of e-cigarettes relative to nicotine. While the findings primarily suggest either no or positive effect of e-cigarettes on cognition in cigarette smokers, associations between e-cigarettes and cognitive impairments in memory, concentration and decision making were reported in both cigarette smokers and never-smokers. Implications and conclusions: The acute cognitive effect of e-cigarettes on regular cigarette smokers appears minimal. However, long-term cognitive effect and their effects on never-smokers are unclear. Given that the increased numbers of e-cigarette users are non-smokers and/or adolescents, research with those naïve to nicotine and a developmentally vulnerable adolescent population on its long-term effect is needed. [ABSTRACT FROM AUTHOR]

Tobacco-free nicotine pouches are new nicotine products for oral consumption. They can contain very high nicotine amounts that have not been addressed with clinical studies yet. Thus, nicotine delivery, effects on craving, and side effects were assessed using pouches with up to 30 mg nicotine. In this single-center, five-arm, crossover study, 15 regular cigarette smokers consumed tobacco-free nicotine pouches from different brands with 6, 20, and 30 mg for 20 min. Comparators were nicotine-free pouches and tobacco cigarettes. At baseline and predefined time points over a study period of 240 min, plasma nicotine concentrations, effects on cigarette craving, and side effects were assessed. Cardiovascular parameters including arterial stiffness were measured using a MobilOGraph. Consumption of 30 mg nicotine pouches has led to a higher nicotine uptake compared with the cigarette (Cmax: 29.4 vs 15.2 ng/mL; AUC: 45.7 vs 22.1 ng/mL × h). Nicotine uptake in the acute phase was rapid during use of the 30 mg pouch and cigarette. Extraction rate of nicotine differed between pouches. Use of all products has reduced acute cigarette craving, even the nicotine-free pouch. During consumption of the cigarette and the pouches with 20 and 30 mg, heart rate increased about 27, 12, and 25 bpm, respectively. Parameters for arterial stiffness were elevated and all pouches have induced mouth irritations. The pouches with 30 mg nicotine had overall the strongest side effects and may induce addiction. As craving was also reduced by products with less nicotine, it is questionable whether such high nicotine contents should be allowed on the market. A limit of nicotine content is warranted. The nicotine release rate varies across products and needs to be known to estimate the nicotine delivery. [ABSTRACT FROM AUTHOR]

Rationale: Nicotine is a principal psychoactive agent in tobacco, contributing to tobacco's addictive potential. Preclinical studies on the effects of voluntary nicotine intake typically use self-administration procedures that provide continuous nicotine access during each self-administration session. However, many smokers consume cigarettes intermittently rather than continuously throughout each day. For drugs including cocaine and opioids, research in laboratory rats shows that intermittent intake can be more effective than continuous intake in producing patterns of drug use relevant to addiction. Objective: We determined how intermittent versus continuous nicotine self-administration influences nicotine seeking and taking behaviours. Methods: Female and male rats had continuous (i.e., Long Access; LgA, 6 h/day) or intermittent (IntA; 12 min ON, 60 min OFF, for 6 h/day) access to intravenous nicotine (15 µg/kg/infusion), for 12 daily sessions. We then assessed intake, responding for nicotine under a progressive ratio schedule of drug reinforcement and cue- and nicotine-induced reinstatement of drug seeking. We also estimated nicotine pharmacokinetic parameters during LgA and IntA self-administration. Results: Overall, LgA rats took twice more nicotine than did IntA rats, yielding more sustained increases in estimated brain concentrations of the drug. However, the two groups showed similar motivation to seek and take nicotine, as measured using reinstatement and progressive ratio procedures, respectively. Conclusions: Intermittent nicotine use is just as effective as continuous use in producing addiction-relevant behaviours, despite significantly less nicotine exposure. This has implications for modeling nicotine self-administration patterns in human smokers and resulting effects on brain and behaviour. [ABSTRACT FROM AUTHOR]

Background: Insular subdivisions show distinct patterns of resting state functional connectivity with specific brain regions, each with different functional significance in chronic cigarette smokers. This study aimed to explore the altered dynamic functional connectivity (dFC) of distinct insular subdivisions in smokers. Methods: Resting-state BOLD data of 31 smokers with nicotine dependence and 27 age-matched non-smokers were collected. Three bilateral insular regions of interest (dorsal, ventral, and posterior) were set as seeds for analyses. Sliding windows method was used to acquire the dFC metrics of different insular seeds. Support vector machine based on abnormal insular dFC was applied to classify smokers from non-smokers. Results: We found that smokers showed lower dFC variance between the left ventral anterior insula and both the right superior parietal cortex and the left inferior parietal cortex, as well as greater dFC variance the right ventral anterior insula with the right middle cingulum cortex relative to non-smokers. Moreover, compared to non-smokers, it is found that smokers demonstrated altered dFC variance of the right dorsal insula and the right middle temporal gyrus. Correlation analysis showed the higher dFC between the right dorsal insula and the right middle temporal gyrus was associated with longer years of smoking. The altered insular subdivision dFC can classify smokers from non-smokers with an accuracy of 89.66%, a sensitivity of 96.30% and a specify of 83.87%. Conclusions: Our findings highlighted the abnormal patterns of fluctuating connectivity of insular subdivision circuits in smokers and suggested that these abnormalities may play a significant role in the mechanisms underlying nicotine addiction and could potentially serve as a neural biomarker for addiction treatment. [ABSTRACT FROM AUTHOR]

Introduction IQOS was authorized by the U.S. Food and Drug Administration (FDA) as a modified-risk tobacco product. We conducted a pharmacokinetic study evaluating the nicotine delivery and subjective effects of IQOS use among current menthol cigarette smokers to better understand if IQOS is an acceptable cigarette alternative in light of the proposed menthol cigarette ban. Aims and Methods Participants were adult smokers of >4 menthol cigarettes per day. After 14-hour nicotine abstinence, participants were provided an IQOS device and menthol heatstick to puff every 20 seconds for a total of 14 puffs. Blood samples were collected at baseline and during active use to calculate nicotine boost from baseline to peak concentration. Nicotine withdrawal symptoms were collected before and after IQOS use. In addition, a modified Product Evaluation Scale for IQOS was collected after use. Results Participants (n = 8) were a mean age of 43.9 years, 63% were female, 88% identified as White, and they smoked a mean of 17.1 menthol cigarettes per day. After IQOS use, the mean nicotine boost obtained was 15.96 ng/mL (SD = 6.91) (range 9.31 to 30.55 ng/mL). Most (75%) participants reported enjoying use of the product "a lot" or greater and more than half (62.5%) reported reduced cigarette cravings. Most participants reported no side effects after use; however, two experienced dry mouth, three experienced dizziness, one experienced throat irritation, and one experienced headache. Conclusion We found that directed use (14 puffs) of menthol IQOS delivered a mean nicotine boost of 15.96 ng/mL which reduced craving for a cigarette. The majority of participants enjoyed use of IQOS and reported mild side effects. Implications Menthol IQOS delivered a sufficient dose of nicotine perceived as satisfying by menthol cigarette smokers and it reduced craving with mild side effects. Menthol IQOS has potential to serve as a less harmful alternative for menthol cigarette smokers. The availability of modified risk products like IQOS should be considered by FDA's Comprehensive Plan for Tobacco and Nicotine Regulation. [ABSTRACT FROM AUTHOR]

Introduction: Consumer preferences should be important factors that are considered when developing health policies and interventions. This paper examines the prevalence of, and factors associated with, consumer preferences regarding smoking behaviour 1 to 2 years in the future. Methods: At least weekly cigarette smokers in the 2020 wave of the International Tobacco Control Four Country Smoking and Vaping Survey (USA, Canada, England and Australia) (N = 8642) were asked if they preferred to continue to smoke or to quit with or without an alternative nicotine product (ANP) over the next 1–2 years. Results: Country‐specific weighted data showed 21.5% preferred to continue smoking and 8.0% were uncertain, leaving 70.6% preferring to quit: 13.7% using an ANP and 56.9% completely quitting nicotine. Apart from interest in quitting, the main predictors of preferring to quit were history of vaping, being aged 55 and over, smoking weekly, worrying about smoking harms, regretting starting and believing vaping is less harmful relative to smoking. Among those preferring to quit, preferring to use ANPs in future was very strongly associated with current vaping (especially daily), being younger, living in England, reporting strong urges to smoke, believing vaping is much less harmful than smoking, and not strongly regretting starting to smoke, and not wanting to quit. Discussion and Conclusions: A significant minority of smokers preferred not to quit, at least in the next year or two. Both interest in quitting and preference for ANPs over complete cessation were associated with similar covariates, including interest in vaping. [ABSTRACT FROM AUTHOR]

Background: Smoking is a major preventable risk factor for cardiovascular morbidity and mortality. Tobacco smoking induces atherosclerosis, ischemic heart diseases, and arrhythmias. The impact of electronic cigarettes on cardiovascular health is still controversial. This study aimed to evaluate the electrocardiographic parameters in chronic electronic cigarette users compared to chronic conventional cigarette smokers and a non-smoker control group of matched age and gender. Results: The study involved 105 volunteers with no history of chronic or cardiovascular diseases or cardioactive drug use. Participants were assigned into three study groups, chronic e-cigarette users, conventional cigarette smokers, and non-smokers, each consisting of 35 participants. Demographic data, smoking history, vital signs, and 12-lead electrocardiogram (ECG) were evaluated. Demographic data were insignificantly different among all study groups. The mean heart rate was significantly higher in chronic electronic cigarette users and conventional cigarette smokers compared to non-smokers (p < 0.001).QRS complex duration was significantly shorter in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). Prolonged QT and QTc intervals duration were recorded in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). All the ventricular repolarization indices (T wave—peak to T-end (Tpe) interval, TPe/QT ratio, and TPe/QTc ratio were significantly prolonged in chronic e-cigarette users, and conventional smokers compared to non-smokers (p < 0.001). Mean systolic, diastolic blood pressure, P wave amplitude and duration, and PR interval were insignificantly different between all groups (P > 0.05). Conclusions: Chronic e-cigarette use is associated with higher heart rates, shorter QRS complex, prolonged QT, QTc duration, and prolonged ventricular repolarization indices compared to non-smokers of matched age and gender. Conclusively, e-cigarette use is associated with negative cardiovascular effects like conventional cigarette smoking. [ABSTRACT FROM AUTHOR]

Aims: Cigarette smoking is a preventable risk factor for various diseases such as cancer, ischemic stroke, cardiac stroke, and chronic obstructive pulmonary disease. Smoking cessation is of great importance not only for individual smokers but also for social health. Regarding current cessation therapies, the effectiveness of nicotine replacement is limited, and the cost of varenicline medication is considerable. Thus, a method for screening smokers who are responsive to cessation therapy based on the therapeutic effectiveness is required. Peripheral biomarkers reflecting smoking dependence status are necessary to establish a method for achieving effective cessation therapy. Methods: Methylation status of smokers' blood DNA was evaluated focusing on SHATI/NAT8L, an addiction‐related gene. Eight CpG sites in SHATI/NAT8L were quantified by pyrosequencing. Results: There was no difference in the methylation status of this gene between smokers (n = 129) and non‐smokers (n = 129) at all CpG sites. No correlations between the methylation status of SHATI/NAT8L and indicators of smoking dependence were found. Conclusions: Although the present study found no significance in the DNA methylation of SHATI/NAT8L among smokers, the exploration of predictable peripheral biomarkers for the effectiveness of smoking cessation therapy is required. [ABSTRACT FROM AUTHOR]

Background: Oral nicotine pouches (ONPs) are novel products, gaining popularity and marketed as "tobacco-free" alternatives to cigarettes and smokeless tobacco (SLT), but their public health impact is unknown. This study qualitatively examined ONP appeal and perceptions among cigarette smokers and SLT users from Ohio Appalachia. Methods: In 2022, we conducted 10 virtual focus groups with smokers (n = 19) and smokeless tobacco users (n = 18) from Appalachia Ohio aged ≥21 to examine perceptions of risks and benefits, substitutability for cigarettes and SLT, and ONP marketing. We transcribed focus groups verbatim, thematically coded transcripts, and analyzed coded data for prominent themes. Results: Participants perceived ONPs to have similar or less risk than cigarettes/SLT but prominently discussed gastrointestinal and cardiovascular risks. Addiction risk was thought to be comparable to cigarettes/SLT, citing "nicotine is nicotine." Participants viewed ONPs to be situational rather than complete substitutes for cigarettes/SLT, viewing them as "cleaner," more socially acceptable, and discrete. Despite appealing features of ONP marketing, participants surmised ads would appeal to youth, new users, tobacco users seeking to cut down/quit, or to "high class," "white-collar" demographics. Conclusions: Participants' perceptions of ONPs and their marketing suggest ONPs are more likely to be used as situational versus complete substitutes for cigarettes and SLT. While situational substitution could exacerbate disparities in Appalachia by facilitating more frequent tobacco/nicotine use, complete substitution could reduce disparities. Research is needed to understand how perceptions, the appeal of ONP marketing, and novel product features translate to patterns of use to understand ONPs' potential impact. [ABSTRACT FROM AUTHOR]

Background: Nicotine is the addictive substance present in tobacco which makes quitting tobacco difficult. Objective: This study was done to assess nicotine dependence and stage of readiness to change among tobacco users visiting the Tobacco Cessation Clinic (TCC) Lucknow. Materials and Methods: A cross-sectional study was performed in the TCC of a Government Dental College. The data were recorded in the tobacco cessation registration forms of tobacco users and then analyzed through statistical software using the Chi-square test. Results: The number of tobacco users was more in males (88%) than in females (12%) with a preference for smokeless type (63.4%) of tobacco usage. Most of the tobacco users were of 25–34 years of age group (34.9%). It was also observed that the maximum number of tobacco users was married (68.3%) and had graduate/postgraduate degree (62.3%). It was also seen that usually, the monthly expense on tobacco products by either gender was Rs. 1000–2400. More than 50% of the tobacco users had tried quitting before because of health issues and craving was the main reason for relapse. We also observed that the highest level of nicotine dependence was amongst the smokeless tobacco users with a history of 5–10 years of tobacco use (43.3%). Conclusion: It was found that most of the patients who attended the TCC had medium level of dependence on nicotine and where in the preparation phase to quit the habit. [ABSTRACT FROM AUTHOR]

Introduction: In the quest of articulating customized tobacco cessation strategies, evaluation of the level of nicotine dependence among participants is quintessential. Objective: This study was conducted to assess the levels of nicotine dependence and its association with age and socioeconomic status among patients seeking oral health care at a teaching dental institution in coastal Andhra Pradesh. Materials and Methods: This cross-sectional study was done among 199 participants with the habit of cigarette smoking who participated in the study. Nicotine dependence scores were assessed using Fagerström Test for Nicotine Dependence (FTND). IBM SPSS version 20 software was used for data analysis. The Chi-square tests and Kruskal–Wallis analyses of variance were done to analyze the study data. P ≤0.05 was considered statistically significant. Results: The mean FTND score was 4.52 ± 2.1. Significant differences in the mean nicotine dependence score were found between different age groups (P < 0.001) and participants belonging to different socioeconomic strata (P < 0.001). While a positive correlation was observed between age and FTND score, an inverse relation was noted between FTND score and socioeconomic status with participants from lower socioeconomic status demonstrating higher FTND scores. The majority of the participants reported smoking <10 cigarettes per day. Conclusion: The study participants demonstrated moderate nicotine dependence. The assessment of nicotine dependence scores as a preliminary step in tobacco cessation counseling is essential to effectively articulate customized cessation strategies. [ABSTRACT FROM AUTHOR]

Monoamine oxidase (MAO) activity is reduced in cigarette smokers and this may promote the reinforcing actions of nicotine, thereby enhancing the addictive properties of cigarettes. At present, it is unclear how cigarette smoking leads to MAO inhibition, but preclinical studies in rodents show that MAO inhibition increases nicotine self-administration, especially at low doses of nicotine. This effect of MAO inhibition develops slowly, likely due to plasticity of brain monoamine systems; studies relying on acute MAO inhibition are unlikely to replicate what happens with smoking. Given that MAO inhibition may reduce the threshold level at which nicotine becomes reinforcing, it is important to consider this in the context of very low nicotine content (VLNC) cigarettes and potential tobacco product regulation. It is also important to consider how this interaction between MAO inhibition and the reinforcing actions of nicotine may be modified in populations that are particularly vulnerable to nicotine dependence. In the context of these issues, we show that the MAO-inhibiting action of cigarette smoke extract (CSE) is similar in VLNC cigarettes and cigarettes with a standard nicotine content. In addition, we present evidence that in a rodent model of schizophrenia the effect of MAO inhibition to enhance nicotine self-administration is absent, and speculate how this may relate to brain serotonin systems. These issues are relevant to the MAO-inhibiting effect of cigarette smoking and its implications to tobacco product regulation. [ABSTRACT FROM AUTHOR]

Background: Novel nicotine delivery devices (NNDDs) are a safer alternative to combustible tobacco smoking. Understanding what factors can facilitate people who smoke to use NNDDs can inform intervention design and public health messaging. This study aims to explore the facilitators and barriers to NNDD use from the perspective of smokers without prior use, after trialling two NNDDs. Method: UK adults who smoke combustible cigarettes (n = 11) were recruited from a larger quantitative study after trialling two NNDDs, an electronic cigarette and a heated tobacco product (order randomly allocated). Semi-structured interviews were conducted, transcribed and thematically analysed, using the COM-B model of behaviour and NVivo12 pro software. Results: Five main themes were identified: health knowledge, availability of and accessibility to NNDD products, cost, social acceptance, and NNDD use experience. There was curiosity and interest in the uptake and use of NNDDs, but the absence of centralised product information was identified as a barrier. Other themes were related to the design and functionality of the NNDD products. For example, the e-cigarette with its low maintenance was seen as easier to use than the heated tobacco product, which offered too short a single use duration and was described as 'cumbersome'. Throat discomfort and high anticipated cost were among additional barriers identified for both product types. Conclusion: This study highlights the need for reliable objective information on the health effects of NNDDs compared with combustible cigarettes, which could facilitate their regular use. Product adjustment such as single use duration alignment with combustible cigarette smoking duration may encourage uptake. Interventions offering opportunity for experience of NNDD use and knowledge dissemination of NNDDs could increase motivation to adopt harm reducing behaviours as demonstrated in this study. [ABSTRACT FROM AUTHOR]

Objectives: Midwakh is a popular form of smoking in the Middle East. This study aimed to assess the predictors of nicotine dependence among cigarette or midwakh smokers in the United Arab Emirates (UAE). Methods: This cross-sectional study was conducted from September to December 2015 in Ajman, UAE. A convenience sampling strategy was implemented to recruit adult male smokers aged =18 years who exclusively smoked either cigarettes or midwakh. A validated self-administered questionnaire was used to collect data from the participants, with nicotine dependence assessed using the Modified Fagerström Test for Nicotine Dependence. In addition, the levels of salivary cotinine and exhaled breath carbon monoxide (CO) were measured. Results: Of the 88 adult male smokers included in the study, 40 (45.5%) were cigarette smokers and 48 (54.5%) smoked midwakh. The majority of participants were 26-35 years of age (48.9%), followed by 18-25 years (30.7%) and >35 years (20.5%). Midwakh use was associated with more than a three-fold increase in the risk of moderate-to-high nicotine dependence compared to cigarette smoking. Moreover, for each unit increase in CO level, there was a 10% increase in the risk of nicotine dependency. There was also a significant association between nicotine dependence level and depth of inhalation (P = 0.023). Conclusion: Type of smoking and CO level were found to be significant predictors of nicotine dependence among adult male smokers. In particular, greater dependency was observed among midwakh smokers than cigarette smokers. [ABSTRACT FROM AUTHOR]

Introduction: Heated tobacco products (HTP) have diversified global tobacco markets, and user characteristics remain understudied. This study evaluated sociodemographic characteristics, nicotine-related perceptions, and behaviors of current HTP users within a sample of adult (18+ years) nicotine users across four countries.Aims and Methods: Data were from current smokers or nicotine vaping product (NVP; known as "e-cigarettes") users from Canada, England, the United States, and Australia (n = 11 421) who participated in the 2018 ITC Four Country Smoking and Vaping Survey. Current (at-least-monthly) HTP users were characterized (n = 441), and weighted multivariable logistic regressions examined correlates of HTP use.Results: Compared to nonusers, current HTP users were younger (mean age: 44.4 vs 31.0 years; p < .001) and had higher socioeconomic status (p < .001). A majority of current HTP users used HTPs nondaily (daily: 40.3% vs nondaily: 59.7%). Most HTP users concurrently used both cigarettes and NVPs (90.5%). Among concurrent cigarette-HTP-NVP users, 36.2% used all three products daily. Use of other combusted tobacco products (cigars, cigarillos, pipe, waterpipe/hookah), cannabis, and binge drinking were each associated with current HTP use. HTP use was more common among smokers intending to quit within 6 months or reporting a quit attempt in the past 18 months, and vapers who had experienced negative side effects.Conclusion: HTP users in this sample tended to be younger and more affluent. Most reported concurrent use of multiple nicotine products and other substances. Those cigarette smokers who used HTPs appeared more interested in smoking cessation, while some characteristics of concurrent HTP-NVP users were suggestive of dissatisfaction with NVPs.Implications: Few studies have scrutinized characteristics of HTP early adopters in emerging markets. Our results indicate that in 2018, characteristics of established nicotine users who adopted HTP use in four high-income Western countries mirror those of HTP users in East Asian markets (South Korea and Japan) where HTPs are popular. HTP users reported high levels of concurrent use of noncigarette-combusted tobacco products (e.g., cigars, pipe tobacco). These findings point to the need for future longitudinal studies of HTP use given the implications of those use patterns on the harm reduction potential of HTPs. HTP user characteristics may yield important information to consider in regulation of these products. [ABSTRACT FROM AUTHOR]

Background:Cigarette smoking is a complicated, psychic, motor and pharmacological act.Cigarette has been reported to contain 500 agents, out of which nicotine present in the tobacco smoking has been thought to be the most offending one. Many of the pharmacological affects of nicotine are known to be the result of complex interactions at different levels of the central nervous system.But damaging effects only become measurable several years or even decades after the start of smoking. Therefore study is required to know the effects ofshort term cigarette smoking on cognitive performances whichcan be measured in terms of response times. Objectives: 1.To study the response times to visual, auditory and cutaneous stimuli in short term cigarette smokers, 2. To study the immediate effect of smoking of one cigarette among smokers on response times.Material and Methods:Thirty male healthy cigarette smokers of age group 20-30 years, drawn from population of Hubli were studied for visual, auditory and cutaneous response times. The results were compared with equal number of age and sex-matched controls. Response times were measured by an instrument called Response analyser.Results:1.The difference in the response times between control group and shortsmoker group, (before smoking) is not statistically significant, 2.Among smokers, smoking a cigarette significantly [statistically]shortens response times, 3.The response times after smokinga cigarette, are also significantly [statistically]shorter than the control values.Conclusion:1)Although response times are shorter in the smokers before smoking than control subjects, the difference is not statistically significant, 2)However, immediately after smoking a cigarette, the response times (R.T) are significantly shortened among smokers. [ABSTRACT FROM AUTHOR]

Many harmful and potentially harmful constituents are present in tobacco products. Cigarette smoke is known to cause different forms of cancer and trigger the development of chronic diseases. In the last decade, electronic cigarettes have emerged as a healthier alternative associated to less harmful effects in comparison to traditional tobacco. However, the lack of standardization of electronic cigarettes products makes it difficult to establish and compare the real effects on health of products from different manufacturers. To better understand the impact of smoking and vaping, the volatomic composition of urine samples from traditional tobacco smokers and electronic cigarette users was established and compared with nonsmokers (control group), using headspace solid‐phase microextraction combined with gas chromatography–mass spectrometry. A total of 45 urinary volatile organic metabolites belonging to different chemical families were identified in the urine of the studied groups. Benzene derivatives, terpenes, and aromatics were the chemical families that contributed the most to the urinary profile of smokers. The vapers urinary volatomic pattern was also dominated by terpenes and aromatics, in addition to alcohols. The orthogonal partial least squares‐discriminant analysis of the data obtained indicated that the urinary profile of vapers is more closely related to the control group, reinforcing the hypothesis of the lowest harmfulness of electronic cigarettes. Further studies recruiting a higher number of subjects are therefore necessary to consolidate the data obtained. [ABSTRACT FROM AUTHOR]

Background and Aims: For electronic cigarettes (e‐cigarettes) to be a viable substitute for combustible cigarettes, it is likely that they must be rewarding enough for regular use, indicated by factors such as craving and dependence, important aspects of reinforcement. This study aimed to understand short‐term changes in measures of nicotine dependence between groups differing by use trajectory in a switching trial, and within group changes of these measures. Design Secondary data analysis of one arm of an e‐cigarette randomized clinical trial. Setting: San Diego, California and Kansas City, Missouri, United States. Participants: 114 African American (n = 60) and Latinx (n = 54) smokers (58.8% male) attempting to switch to nicotine salt pod system (NSPS) e‐cigarettes in a 6‐week trial. Measurements At week 6, participants were classified by use trajectory: exclusive smokers (n = 16), exclusive e‐cigarette (n = 32), or dual users (n = 66). E‐cigarette, cigarette, and total nicotine dependence (cigarette + e‐cigarette), use patterns, cigarette craving and nicotine withdrawal, and cotinine were assessed at baseline and week 6 using standard measures. Findings In between group comparisons, exclusive e‐cigarette and dual users showed greater reductions in cigarette dependence (e‐cigarette: −32.38, 95% CI = −37.7,−27.1; dual: −18.48, 95% CI = −22.2,−14.7), withdrawal (e‐cigarette: −6.25, 95% CI = −8.52,−3.98; dual: −3.18, 95% CI = −5.02,−1.34), craving (e‐cigarette: −11.44, 95% CI = −14.2,8.7; dual: −9.59, 95% CI = −11.6,−7.59), and cigarettes per day (CPD; e‐cigarette: −11.19, 95% CI = −13.1,−9.27; dual: −9.39, 95% CI = −11.3, −7.52) compared with exclusive smokers. In within group analyses, e‐cigarette and dual users showed reductions in craving and withdrawal from baseline to week 6. Exclusive e‐cigarette and dual users, maintained cotinine levels (all Ps > 0.05) and showed reductions in CPD and cigarette dependence (all Ps < 0.01). Findings were inconclusive regarding changes in total nicotine dependence from baseline to week 6 among exclusive e‐cigarette users (P = 0.123). Dual users showed increased total nicotine dependence (P < 0.001) and smokers showed decreased total dependence (P = 0.004). Conclusions: Smokers who switch to nicotine salt pod system e‐cigarettes maintain their nicotine levels and transfer their dependence, suggesting that nicotine salt pod system e‐cigarettes have a similar reinforcement potential to cigarettes and facilitate switching. [ABSTRACT FROM AUTHOR]

Introduction: Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants.Methods: This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers.Results: In JUUL groups, median percent reductions in primary BOEs (Day 6-Baseline) were 90%-≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps < 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%-55% of Abstinence. Similar results were observed for secondary BOEs.Conclusion: This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking.Implications: This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System ("JUUL") in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking. [ABSTRACT FROM AUTHOR]

2-Hydroxyethyl mercapturic acid (2HEMA, N-acetyl-S-(2-hydroxyethyl)-L-cysteine) is a urinary metabolite of several volatile organic compounds including acrylonitrile and ethylene oxide, which are found in cigarette smoke. We measured 2HEMA concentrations in urine specimens collected during the National Health and Nutrition Examination Survey (2011–2016) from eligible participants aged >12 years (N = 7,416). We developed two multiple linear regression models to characterize the association between cigarette smoking and 2HEMA concentrations wherein the dependent variable was 2HEMA concentrations among participants who exclusively smoked cigarettes at the time of specimen collection and the independent variables included sex, age, race/ethnicity, creatinine, diet, and either cigarettes smoked per day (CPD) or serum cotinine. We detected 2HEMA in 85% of samples tested among exclusive cigarette smokers, and only 40% of specimens from non-smokers. When compared to exclusive cigarette smokers who smoked 1–9 CPD, smoking 10–19 CPD was associated with 36% higher 2HEMA (p < 0.0001) and smoking >19 CPD was associated with 61% higher 2HEMA (p < 0.0001). Additionally, 2HEMA was positively associated with serum cotinine. This study demonstrates that cigarette smoking intensity is associated with higher urinary 2HEMA concentrations and is likely a major source of acrylonitrile and/or ethylene oxide exposure. [ABSTRACT FROM AUTHOR]

Introduction: This study explores patterns of use of non-cigarette tobacco and nicotine products among adult cigarette smokers and recent ex-smokers. Along with cigarette smoking status we explore differences as a function of countries with different product regulations, gender, and age.Methods: Data came from the ITC Four Country Smoking and Vaping Wave 3 Survey conducted between February-June 2020. The analytic sample consisted of 9112 current cigarette smokers (at least monthly) and 1184 recent ex-smokers (quit cigarettes ≤ 2 years) from Australia, Canada, England, and the United States. Respondents were asked about their cigarette smoking and current use of the following non-cigarette products: combustible tobacco (cigars, cigarillos, pipe, waterpipe); noncombustible tobacco (smokeless tobacco, and heated tobacco products [HTPs]); and non-tobacco nicotine products (nicotine vaping products [NVPs], nicotine replacement therapy [NRT], and nicotine pouches).Results: Overall, NVPs (13.7%) and NRT (10.9%) were the most reported nicotine products used, followed by cigars (5.3%), cigarillos (4.2%), and HTPs (3.5%). More than 21% current and recent ex-smokers of cigarettes reported using a non-tobacco nicotine product and noncombustible product, with respondents in England reporting the highest levels of use (>26%). Males, younger respondents, and current non-daily cigarette smokers were more likely to use non-cigarette nicotine products. Notably, 11.6% of ex-cigarette smokers were using other combustible tobacco.Conclusion: Considerable percentages of current cigarette smokers and ex-smokers use non-cigarette nicotine products, and there are unexpectedly high levels of use of other combustible products by those recent ex-smokers of cigarettes which is concerning and has important implications for definitions of smoking cessation.Implications: The tobacco product market has evolved to include new products which add to existing non-cigarette tobacco products creating a much more diverse nicotine market. This brief report provides a snapshot of use of various combustible and noncombustible nicotine-containing products among current cigarette smokers and recent ex-smokers in four western countries. Our results indicate that use of non-cigarette tobacco and nicotine products among these cigarette smokers and recent ex-smokers is not low, particularly among males, younger and non-daily cigarette smokers. Use of other combustible tobacco among respondents that recently quit cigarette smoking is concerning and has important implications for definitions of smoking cessation. Increased emphasis on researching non-cigarette nicotine product use is warranted in tobacco control generally and smoking cessation in particular. [ABSTRACT FROM AUTHOR]

Cross-sectional survey data (N = 3264) from the National Health and Nutrition Examination Survey for 2013–2018 were used to investigate how serum hydroxycotinine concentrations vary among US adult smokers aged ≥ 20 years by smoker type. Those reporting using tobacco products during the last 5 days were classified as smokers. Smokers were classified as being cigarette only smokers, cigar only smokers, cigar and cigarette smokers, dual cigarette and e-cigarette smokers, e-cigarette only smokers, smokeless tobacco only users, and all other smokers. Regression models stratified by smoker type with log10 transformed values of serum hydroxycotinine as dependent variable were fitted to compute adjusted geometric means (AGM) for each type of smoker. The order in which various types of smokers were found to have AGMs for serum hydroxycotinine was cigarette and e-cigarette users (64.61 ng/mL), cigarette only smokers (53.17 ng/mL), smokeless tobacco only users (44.89 ng/mL), cigar and cigarette smokers (36.99 ng/mL), e-cigarette only users (32.52 ng/mL), smokers of miscellaneous tobacco products (20.32 ng/mL), and cigar smokers only (10.75 ng/mL). Compared to this as presented in a recent study, the order in which serum cotinine AGMs were: smokeless tobacco only users (272 ng/mL), cigarette only smokers (152.5 ng/mL), cigarette-e-cigarette or e-cigarette only users (146.3 ng/mL), smokers of miscellaneous tobacco products (105.5 ng/mL), cigar and cigarette smokers (92.5 ng/mL), cigar smokers only (65.1 ng/mL). Among cigarette only smokers, males had lower AGM than females (47.18 vs. 59.91 ng/mL, p < 0.01), but the reverse was true for smokeless tobacco only and miscellaneous smokers. In general, differences for hydroxycotinine levels did not exist among non-Hispanic white and non-Hispanic black smokers. Among US adults, cigarette only and dual cigarette-e-cigarette smokers had the highest, and cigar smokers had the lowest concentrations of serum hydroxycotinine. [ABSTRACT FROM AUTHOR]

The formation of carbonyls and epoxides in e-cigarette (EC) aerosol is possible due to heating of the liquid constituents. However, high background levels of these compounds have inhibited a clear assessment of exposure during use of ECs. An EC containing an e-liquid replaced with 10% of 13C-labeled propylene glycol and glycerol was used in a controlled use clinical study with 20 EC users. In addition, five smokers smoked cigarettes spiked with the described e-liquid. Seven carbonyls (formaldehyde, acetaldehyde, acrolein, acetone, crotonaldehyde, methacrolein, propionaldehyde) were measured in the aerosol and the mainstream smoke. Corresponding biomarkers of exposure were determined in the user's urine samples. 13C-labeled formaldehyde, acetaldehyde and acrolein were found in EC aerosol, while all seven labeled carbonyls were detected in smoke. The labeled biomarkers of exposure to formaldehyde (13C-thiazolidine carboxylic acid and 13C-N-(1,3-thiazolidine-4-carbonyl)glycine), acrolein (13C3-3-hydroxypropylmercapturic acid) and glycidol (13C3-dihydroxypropylmercapturic acid) were present in the urine of vapers indicating an EC use-specific exposure to these toxicants. However, other sources than vaping contribute to a much higher extent by several orders of magnitude to the overall exposure of these toxicants. Comparing data for the native (unlabeled) and the labeled (exposure-specific) biomarkers revealed vaping as a minor source of user's exposure to these toxicants while other carbonyls and epoxides were not detectable in the EC aerosol. [ABSTRACT FROM AUTHOR]

Electronic nicotine delivery systems (ENDSs) are used by some smokers to reduce cigarette consumption, but their effectiveness is uncertain. We aimed to examine the extent to which ENDSs or a non-nicotine cigarette substitute influence tobacco-related toxicant exposure and cigarette consumption in smokers interested in smoking reduction. We did a four-arm, parallel-group, randomised controlled trial at two sites in the USA (Penn State University, Hershey, PA, and Virginia Commonwealth University, Richmond, VA). We enrolled adults aged 21–65 years who smoked more than nine cigarettes per day (for at least the past year), with exhaled CO of more than 9 parts per million at screening, who were not currently using an ENDS, and who were interested in reducing smoking but not quitting. Participants were randomised (site-specific with allocation concealment; 1:1:1:1) to receive either a cartomiser-based, pen-style ENDS (eGo-style) paired with 0, 8, or 36 mg/mL liquid nicotine (participants and researchers masked to concentration) or a non-ENDS cigarette-shaped plastic tube that delivered no nicotine or aerosol (cigarette substitute; unmasked) for 24 weeks. Conditions were chosen to reflect a range of nicotine delivery including none (cigarette substitute and 0 mg/mL ENDS), low (8 mg/mL), and cigarette-like (36 mg/mL), and all conditions were paired with smoking reduction instructions. The primary outcome was concentration of the tobacco-specific carcinogen metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; urinary total) collected at randomisation and at 4, 12, and 24 weeks. Multiple imputation with and without covariate adjustment was used in addition to sensitivity analyses. This trial is registered with ClinicalTrials.gov , NCT02342795. Between July 22, 2015, and Nov 16, 2017, 684 individuals were screened and 520 (76%) were enrolled and randomised. 188 (36%) of 520 participants were lost to follow-up by week 24; attrition did not differ by study group (39 [30%] of 130 in the cigarette substitute group, 56 [43%] of 130 in the ENDS with 0 mg/mL nicotine group, 49 [38%] of 130 in the ENDS 8 mg/mL group, and 44 [34%] of 130 in the ENDS 36 mg/mL group). Urinary total NNAL at 24 weeks in the ENDS with 36 mg/mL nicotine group was 210·80 pg/mg creatinine (95% CI 163·03–274·42) compared with 346·09 pg/mg creatinine (265·00–455·32) in the cigarette substitute group (p=0·0061). No other significant differences between groups were observed for any time point for urinary total NNAL. Serious adverse event frequency was similar across groups (12 events in 12 participants [9%] in the ENDS with 36 mg/mL nicotine group, seven events in six participants [5%] in the 8 mg/mL group, 11 events in ten participants [8%] in the 0 mg/mL group, and 13 events in 13 participants [10%] in the cigarette substitute group), and all of these were deemed unrelated or unlikely to be related to study product use. There was one death between randomisation and 24 weeks (suicide; in the ENDS with 0 mg/mL nicotine group). Use of an ENDS with cigarette-like nicotine delivery can reduce exposure to a major pulmonary carcinogen, NNAL, even with concurrent smoking. Future ENDS trials should involve products with well characterised nicotine delivery, including those with nicotine delivery approaching that of a cigarette. National Institutes of Health, US Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Nicotine dependence and smoking quantity are both robustly associated with the CHRNA5-A3-B4 gene cluster in the 15q25 region, and SNP rs16969968 in particular. The purpose of this paper is to use structural equation modeling techniques (SEM) to disentangle the complex pattern of relationships between rs16969968, nicotine quantity (as measured by the number of cigarettes an individual smokes per day; CPD) and nicotine dependence (as measured by the Fagerström Test for Nicotine Dependence; FTND). CPD is an indicator, but also a potential cause, of FTND, complicating the interpretation of associations between these constructs and requires a more detailed investigation than standard GWAS or general linear regression models can provide. FTND items and genotypes were collected in four samples, with a combined sample size of 5,373 respondents. A mega-analysis was conducted using a multiple group SEM approach to test competing hypotheses regarding the relationships between the SNP rs16969968, FTND and CPD. In the best fitting model, the FTND items loaded onto two correlated factors. The first, labeled "maintenance," assesses the motivation to maintain constant levels of nicotine through out the day. The second was labeled "urgency" as its items concern the urgency to restore nicotine levels after abstinence. We focus our attention on the "maintenance" factor, of which CPD was an indicator. The best fitting model included a negative feedback loop between the Maintenance factor and CPD. Accordingly, the motivation to maintain higher levels of nicotine increased the quantity of nicotine consumed, which subsequently decreases the maintenance motivation. The fact that the Maintenance-CPD feedback model fits the data best implies that there are at least two biological pathways that lead from rs16969968 to smoking behaviors. The model is consistent with a supply and demand system, which allows individuals to achieve a homeostatic equilibrium for their nicotine concentration. [ABSTRACT FROM AUTHOR]

The composition and metabolic functions of oral microbiota are affected by many factors including smoking leading to several health problems. Cigarette smoking is associated with changes in oral microbiota composition and function. However, it is not known if the depletion of certain bacterial genera and species is due to specific toxins in cigarette smoke, or indirectly due to competition for colonization with smoking-enriched bacteria. Therefore, the aim of this study was to determine the effect of cigarette smoking on the microbial prevalence and polycyclic aromatic hydrocarbons (PAHs) biodegradation of selected enriched and depleted oral bacteria from oral microbiota of smokers compared to that in non-smokers. Samples of oral rinse from smokers and non-smokers were collected (n = 23, 12 smokers and 11 non-smokers) and screened for oral bacterial strains of Streptococcus mutans, Lactobacillus spp., and Veillonella spp. Comparing counts, S. mutans , V. tobetsuensis , and V. dispar showed higher counts in smokers compared to non-smokers while the Lactobacillus spp. were higher in non-smokers. Lactobacillus fermentum was prevalent in smokers, representing 91.67% of the total Lactobacillus spp. isolates. The biodegradation potential of anthracene; a representative of PAHs of collected isolates, in single and mixed cultures, was assayed with anthracene as the sole source of carbon using 2,6-dichlorophenol indophenol (2,6-DCPIP) as indicator. S. mutans isolates recovered from smokers showed higher degradation of anthracene compared to those recovered from non-smokers. The anaerobic anthracene biodegradation activity of V. parvula isolates from non-smokers was the highest among all isolates of the three recovered genera from the same subject. The anthracene biodegradation potential of Lactobacillus spp. was variable. Combinations of isolated bacteria in co-cultures showed that Lactobacillus spp. interfered with anthracene biodegradation ability along with the viable counts of S. mutans and Veillonella spp. In conclusion, oral dysbiosis due to cigarette smoking was observed not only due to changes in oral bacterial relative abundance but also extended to bacterial functions such as anthracene biodegradation tested in this study. Microbe–microbe interactions changed the anthracene biodegradation potential and growth of the microbial mixture compared to their corresponding single isolates, and these changes differ according to the constituting bacteria. [ABSTRACT FROM AUTHOR]

Introduction: This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes in 24 adult smokers.Methods: At five study visits, subjects used either the JS in 59 mg/mL, JS 18 mg/mL (two visits), and JS 9 mg/mL (all tobacco-flavored) or smoked their UB cigarette first during a controlled puffing sequence (CPS) and then ad libitum (5 min) use sessions. Blood samples were taken at specified timepoints for 60 min in each session. The modified Product Evaluation Scale assessed subjective effects 30-min post-use in the CPS session.Results: Maximum plasma nicotine concentration (Cmax-BL), total nicotine exposure (AUC0-60-BL), and rate of plasma nicotine rise were significantly lower for all JS products compared to subjects' UB cigarette in CPS and ad libitum use sessions. In both use sessions these PK parameters were significantly higher for JS 59 mg/mL compared to 18 and 9 mg/mL. Subjective measures of cigarette craving relief and "Enough Nicotine" for JS 59 mg/mL did not differ significantly from UB cigarettes, but JS 18 and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes.Conclusions: Nicotine exposure and subjective relief were directly related to JS nicotine concentration: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving. Heavier and more dependent smokers may require the greater nicotine delivery of JS 59 mg/mL to successfully transition away from cigarettes.Implications: It has been suggested that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes may facilitate smokers transitioning away from cigarettes. We examined nicotine PK and subjective effects of JUUL System (JS) ENDS with three nicotine concentrations (59, 18 and 9 mg/mL) compared to combustible cigarettes. Nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. These findings suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes. [ABSTRACT FROM AUTHOR]

Introduction: The Food and Drug Administration issued an advanced notice of proposed rulemaking for setting a product standard for nicotine levels in cigarettes, with an emphasis on minimally or non-addicting very low nicotine content (VLNC).Methods: A 33 week, two-arm, double-blind randomized trial conducted in Hershey, Pennsylvania, USA and Washington, DC, USA included adult daily cigarette smokers (≥5 cigarettes per day) with less than a college degree, and who had no plans to quit within the next six months. Participants were randomized to either reduced nicotine content (RNC) study cigarettes tapered every three weeks to a final VLNC (0.2 mg/cigarette) for six weeks or to usual nicotine content (UNC) study cigarettes (11.6 mg/cigarette). Outcomes included acceptability of study cigarettes measured by attrition (primary outcome), compliance, reduction in cigarette dependence and tobacco biomarkers, and post-intervention cessation.Results: The RNC (n = 122) versus UNC (n = 123) group had higher attrition (adjusted Hazard Ratio 3.4; 95% confidence interval [CI] 1.99 to 5.81). At the end of the intervention, cotinine levels were 50% lower in the RNC group (mean group difference -137 ng/mL; 95% CI -172, -102). The RNC group smoked fewer CPD (-4.1; 95% CI -6.44, -1.75) and had lower carbon monoxide levels (-4.0 ppm; 95% CI -7.7, -0.4). Forty seven percent (29/62) of the RNC group were biochemically-confirmed compliant with smoking VLNC cigarettes (mean cotinine = 8.9 ng/ml). At three month follow-up, only compliant VLNC smokers quit with an assisted quit attempt (N = 6/22, 27%).Conclusions: This study supports a VLNC standard in cigarettes.Implications: Differential dropout and noncompliance indicate some smokers had difficulty transitioning to cigarettes with reduced nicotine. These smokers will benefit from supplemental nicotine in medicinal or noncombustible tobacco products if a nicotine reduction standard is established. Other smokers successfully transitioned to very low nicotine content cigarettes exclusively and substantially reduced their exposure to nicotine. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the impact of acute and chronic nicotine consumption on measures of intracortical inhibition and facilitation. This study involved 50 chronic heavy cigarette smokers and 40 healthy subjects matched for age, sex and educational level, with no history of chronic nicotine intake. Intracortical inhibition and facilitation were assessed using transcranial magnetic stimulation (TMS) measures of motor threshold (MT), short- and long-interval intra-cortical inhibition (SICI, LICI), cortical silent period (CSP) and intra-cortical facilitation (ICF). Basal serum levels of cotinine were measured in the healthy group and at ½ and 2 h after smoking a single cigarette in the chronic smokers. There was enhanced SICI and reduced ICF in smokers (independent of time after smoking) compared with non-smokers. The former suggests a chronic effect of increased nicotine levels on GABA-A neurotransmission whereas the latter suggests an additional effect on glutamatergic transmission. There were no significant differences between smokers and non-smokers in other TMS parameters. There was a significant negative correlation between cotinine levels at ½ h after smoking and SICI at 3 ms ISI (P < 0.001). There were no significant differences in any of the neurophysiological measures between smokers at ½ h versus 2 h after smoking a single cigarette. Chronic nicotine consumption enhances SICI, and reduces ICF, supporting the hypothesis that nicotine acts as a neuromodulator of GABA-A and glutamate neurotransmission. [ABSTRACT FROM AUTHOR]

Background: Over one-quarter of all smokers in the United States identify as non-daily smokers and this number is projected to rise. Unlike daily smokers who typically maintain consistent levels of nicotine exposure with regular smoking, non-daily smokers have variable patterns of smoking that likely result in high intraindividual variability in nicotine intake. The current study aimed to characterize the weekly intraindividual variability in cotinine and identify smoking-related predictors in nondaily smokers.Methods: An ecological momentary assessment of 60 non-daily smokers ages 24-57 years was conducted over a consecutive 7-day at-home protocol to log each smoking session, assessments of mood and social activity during smoking, and collection of daily saliva samples in a convenience sample from Pennsylvania, USA. Hierarchical linear regression analyses were conducted to determine the effects of smoking characteristics on total cotinine exposure measured by pharmacokinetic area under the curve and the range, maximum, and minimum cotinine values during the week controlling for demographic variables.Results: The mean daily cotinine level was 119.2 ng/ml (SD = 168.9) with individual values that ranged from nondetectable to 949.6 ng/ml. Menthol predicted increased total cotinine levels (P < 0.05). Shorter time to the first cigarette of the day predicted significantly higher minimum (P < 0.05), maximum (P < 0.05), and total cotinine values (P < 0.05) after controlling for covariates. Negative emotions and social interactions with others were also significantly associated with higher cotinine metrics. There was no significant effect of the nicotine metabolite ratio.Conclusions: Our findings highlight the variability in nicotine exposure across days among non-daily smokers and point to the role of smoking context in nicotine exposure. The findings suggest the need to develop better assessment methods to determine health and dependence risk and personalized cessation interventions for this heterogeneous and growing group of smokers. [ABSTRACT FROM AUTHOR]

Aims: To assess the prevalence of the perceived safety of smoking a few (generally fewer than five per day) cigarettes during pregnancy and identify associated factors in a sample of pregnant smokers in Romania, a middle‐income country. Design and Setting: Cross‐sectional design with a convenience sample using a polled data set collected between 2016 and 2019 in the formative and baseline phases of the Quit Together randomized control trial (RCT) in Romania. Data were collected using a structured questionnaire administered by research assistants in clinics in the formative phase and self‐administered through the study website at the RCT baseline. Participants: A total of 217 pregnant smokers (mean age = 28.5 ± 5.8) enrolled in the formative and RCT phases of the research project. Measurements The main outcome was the perceived safety of smoking a few cigarettes during pregnancy (generally fewer than five per day). Covariates included the health‐care providers' advice towards smoking tobacco cigarettes during pregnancy, socio‐demographics, the presence of depression and anxiety symptoms and level of nicotine dependence. Findings More than 35% of participants agreed that smoking a few cigarettes during pregnancy was safe for them and their baby. The perceived safety of smoking a few cigarettes during pregnancy was significantly associated with being told by health‐care providers that it is acceptable to continue to smoke cigarettes in small amounts [odds ratio (OR) = 3.08; 95% CI = 1.35–6.99; P < 0.01], perceived harm reduction of smoking light cigarettes (OR = 2.67; 95% CI = 1.19–5.97; P = 0.02) and moderate to severe depression and anxiety score (OR = 0.34; 95% CI = 0.13–0.84; P = 0.02). Conclusions: More than one‐third of pregnant Romanian women appear to believe that smoking 'a few' cigarettes during pregnancy is safe for them and their fetuses. Those who are told by their health‐care providers that it is acceptable to smoke in small amounts during pregnancy have higher odds of perceiving smoking 'a few' cigarettes during pregnancy as safe compared with other pregnant Romanian women. [ABSTRACT FROM AUTHOR]

The prevalence of concurrent use of combustible and electronic cigarettes (dual-use) is on the rise among Malaysian adolescents. This study compares nicotine dependence among exclusive cigarette users, e-cigarette users, and dual adolescent users. A total of 227 adolescent smokers completed a self-administrated questionnaire with items based on Hooked on Nicotine Checklist (HONC) incorporated. Endorsement of at least one HONC item indicates nicotine dependence. Exhaled carbon monoxide readings and salivary cotinine data were also collected. Over half (52.9%) of the participants were exclusive e-cigarette users (EC). The prevalence of exclusive conventional cigarette smokers (CC) and dual users was 11.9% and 35.2%, respectively. Adolescents who have mothers with secondary school education were more likely to become addicted to nicotine (Adjusted Odd Ratio (aOR) = 2.72; 95% CI = 1.17--6.32). Adolescents' "mother's education" level predicted nicotine dependence. This highlighted the need to target families within the identified demography with a more supportive anti-tobacco program. [ABSTRACT FROM AUTHOR]

Smoking is mainly sustained by nicotine dependence (ND), which varies across ethnic groups principally due to genetic as well as environmental factors. The Fagerström Test for Nicotine Dependence (FTND) and biomarkers of tobacco exposure are two important approaches to assess ND. However, the relationship between ND and FTND of Chinese smokers has not been studied. The aim of this study was to assess the relationship between FTND scores and nicotine, cotinine, 3′-hydroxycotinine (3HC) and nicotine metabolite ratio (NMR, the concentration ratio of 3HC to cotinine) in Chinese smokers. FTND was carried out and general characteristics were collected using a self-administered smoking questionnaire with 289 smokers. Nicotine, cotinine and 3HC in urine were simultaneously determined by liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS). The concentrations of nicotine, cotinine and 3HC in the urine of smokers with a high FTND score were higher than in the urine of those with a low FTND score. There were significant correlations between urinary biomarker and FTND scores. Except for FTND item 2 (difficulty to refrain), the other items showed significant associations with the urinary biomarkers. No relationship was found between the nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) and FTND scores or general characteristics of the participants. In conclusion, biomarkers of tobacco exposure levels are significantly associated with FTND scores. However, FTND Item 2 and NMR were not found to be associated with nicotine dependence in Chinese smokers. [ABSTRACT FROM AUTHOR]

Background and aims: Cigarette smoking often results in nicotine dependence. With use of electronic cigarettes as an alternative source of nicotine, it is important to assess dependence associated with e‐cigarette use. This study assesses dependence among current and former adult e‐cigarette users on cigarettes and e‐cigarettes, compared with dependence on cigarettes. Design Cross‐sectional data from the Population Assessment of Tobacco and Health (PATH) study from 2013–2016. Psychometrically assessed dependence was compared for cigarettes and e‐cigarettes among current and former exclusive and dual users of the products and among e‐cigarette users who had and had not recently stopped smoking. Setting A population‐based representative sample of US adults. Participants Participants were 13 311 US adults (18+) in Waves 1–3 of PATH reporting current established smoking, current use of e‐cigarettes, or stopping use of either product in the past year who were administered dependence assessments for cigarettes and/or e‐cigarettes. Measurements A 16‐item scale assessing tobacco dependence (on a 1–5 scale), previously validated for assessment and comparison of dependence on varied tobacco products, including cigarettes and e‐cigarettes, with a variation assessing residual dependence among users who stopped in the past year. Findings Among current users, dependence on e‐cigarettes was significantly lower than dependence on cigarettes, in within‐subjects comparisons among dual users of both e‐cigarettes and cigarettes (1.58 [SE = 0.05] vs. 2.76 [0.04]), P < 0.0001), and in separate groups of e‐cigarette users and cigarette smokers (1.95 [0.05] vs. 2.52 [0.02], P < 0.0001), and among both daily and non‐daily users of each product. Among former users, residual symptoms were significantly lower for e‐cigarettes than cigarettes, both among former dual users (1.23 [0.07] vs. 1.41 [0.06], P < 0.001) and among users of one product (1.28 [0.03] vs. 1.53 [0.03], P < 0.0001). The highest level of e‐cigarette dependence was among e‐cigarette users who had stopped smoking (2.17 [0.08]). Conclusion Use of e‐cigarettes appears to be consistently associated with lower nicotine dependence than cigarette smoking. [ABSTRACT FROM AUTHOR]

Background: Cannabis smoking and cigarette smoking often co-occur, yet limited research has investigated the potentially different role impulsivity may play when these behaviours occur in isolation, compared with in combination.Aims: This study examined trait and behavioural impulsivity as a function of both cigarette and cannabis smoking.Methods: Trait impulsivity (BIS-11) was compared between 44 non-smokers, 76 cigarette only, 47 cannabis only and 58 cannabis plus cigarette smokers. The effects of cigarette and cannabis smoking on behavioural impulsivity (stop-signal and information sampling tasks) were then assessed in 87 of these participants during a laboratory session.Results: Trait impulsivity was significantly higher in cigarette smokers than non-smokers, irrespective of cannabis use, except for motor impulsivity, where cigarette smoking was only associated with elevated trait impulsivity in non-smokers of cannabis. Dimensions of trait impulsivity were significantly positively related to cigarette smoking frequency and nicotine dependence, but not to cannabis smoking frequency or dependence. Smoking cigarettes or cannabis was associated with significantly impaired reflection impulsivity relative to not smoking either substance. However, no additional increases in reflection impulsivity were observed in those who smoked both cigarettes and cannabis. No group differences in response inhibition were detected.Conclusions: Heightened trait impulsivity appears to be uniquely related to cigarette smoking, whilst the smoking of cigarettes or cannabis is associated with impairments in reflection impulsivity. Improved outcomes for treating cannabis dependence may result from encouraging concomitant cigarette smokers to cease using both drugs simultaneously in order to reduce heightened impulsivity and risk of relapse. [ABSTRACT FROM AUTHOR]

Delay discounting is the process by which a commodity loses value as the delay to its receipt increases. Rapid discounting predicts various maladaptive behaviors including tobacco use. Typically, delay discounting of different outcomes has been compared between cigarette smokers and nonsmokers. To better understand the relationship of delay discounting to different modes of tobacco use, we examined the differences in delay discounting of different outcomes between cigarette smokers, smokeless tobacco users, e‐cigarette users, and non‐tobacco users. In the present study, all participants completed 8 titrating delay‐discounting tasks: $100 gain, $500 gain, $500 loss, alcohol, entertainment, food, a temporary health gain, and a temporary cure from a disease. Non‐tobacco users discounted most outcomes less than tobacco users overall; however, there were no differences in discounting among the different types of tobacco users. These results suggest that nicotine consumption of any kind is associated with a higher degree of impulsivity compared to non‐tobacco users. Adoption of tobacco products that have been perceived as less harmful (e.g., e‐cigarettes) is not associated with a baseline difference or decrease in delay discounting if adopted after a history of cigarette use. [ABSTRACT FROM AUTHOR]

Introduction: A nicotine-reduction policy could have major benefits for smokers with serious mental illness (SMI). However, potential unintended consequences, such as compensatory smoking, should be considered to ensure that such a policy does not negatively affect this population. The purpose of this secondary analysis was to examine the impact of smoking very low nicotine content (VLNC) cigarettes for 6 weeks on smoking topography characteristics, indicators of compensatory smoking, among smokers with SMI.Aims and Methods: After a baseline usual brand smoking phase, smokers with SMI (N = 58) were randomly assigned under double-blind conditions to receive either VLNC (0.4 mg nicotine per g tobacco) or normal nicotine content (NNC; 15.8 mg nicotine per g tobacco) research cigarettes for 6 weeks. During two study visits scheduled 6 weeks apart, participants smoked either their usual brand (baseline) or assigned study cigarettes (postrandomization) through a handheld smoking topography device. Univariate analysis of variance compared smoking topography indices with cigarette condition (VLNC vs. NNC) as the between-subjects factor with corresponding baseline topography results included as covariates.Results: At week 6, participants in the VLNC condition smoked fewer puffs per cigarette and had shorter interpuff intervals compared to participants in the NNC condition (ps < .05). There were no differences between research cigarette conditions at week 6 for cigarette volume, puff volume, puff duration, peak flow rate, or carbon monoxide boost.Conclusions: Findings are consistent with acute VLNC cigarette topography studies and indicate that a nicotine-reduction policy is unlikely to lead to compensation among smokers with SMI.Implications: Given the high smoking rates among people with SMI, understanding how a nicotine-reduction policy may affect this population is critically important. When considering the smoking topography results as a whole, smokers with SMI did not engage in compensatory smoking behavior when using VLNC cigarettes during a 6-week trial. Study findings suggest that compensatory smoking is not likely to occur among smokers with SMI if nicotine content is lowered to minimally addictive levels. [ABSTRACT FROM AUTHOR]

Stress is known to influence smoking relapse. Experimental studies indicate that acute stress increases nicotine-seeking behavior, yet neurobiological mechanisms remain poorly understood. Herein, we investigated disrupted excitatory neural activity in the dorsolateral prefrontal cortex (dlPFC) as a mechanism of stress-induced nicotine-seeking behavior. Non-treatment-seeking cigarette smokers were screened for psychiatric, medical, and neuroimaging contraindications. Using a double-blind, placebo-controlled, randomized crossover design, participants (N = 21) completed two oral-dosing sessions: stress (yohimbine 54 mg + hydrocortisone 10 mg) vs placebo (lactose 54 mg + lactose 10 mg). During each experimental session, working memory proficiency, dlPFC excitatory neural activity, nicotine-seeking behavior, and subjective effects were measured. dlPFC excitatory neural activity was quantified via glutamate modulation during working memory performance using functional proton magnetic resonance spectroscopy. Nicotine-seeking behavior was assayed using a cigarette puffs vs money choice progressive ratio task. Results indicated that yohimbine + hydrocortisone evoked a sustained physiological stress response (elevated heart rate, blood pressure, saliva cortisol, and saliva α-amylase levels; ps < .05). Relative to placebo levels, acute stress increased nicotine-seeking behavior (ps < .05), disrupted dlPFC glutamate modulation (p = .025), and impaired dlPFC function (working memory proficiency; ps < .05). The stress-induced increase in nicotine-seeking behavior was linearly related to the stress-induced disruption of dlPFC glutamate modulation (R2  = 0.24-0.37; ps < .05). These findings suggest that disrupted dlPFC excitatory neural activity is a neurobiological correlate of acute stress-induced nicotine-seeking behavior. These findings further emphasize the central role of the dlPFC in regulating drug-seeking behavior. Future studies are needed to evaluate interventions to improve dlPFC resilience to acute stress effects, including neurostimulation, working memory training, and "anti-stress" medications. [ABSTRACT FROM AUTHOR]

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study. Participants completed two 8-day treatment phases during which they received either CERC-501 (15 mg, p.o., once daily) or placebo. On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing. The primary outcome measures were (a) performance on the McKee Smoking Lapse test (ie, latency to smoke in exchange for money) and (b) number of cigarettes self-administered during a 60-minute ad lib smoking period. Other outcomes included measures of craving, mood, anxiety, nicotine withdrawal, and subjective effects of cigarette smoking. A total of 71 participants who smoked an average of approximately 23 cigarettes per day were enrolled, and 56 subjects completed the study. CERC-501 was well tolerated, but it did not significantly alter the latency to start smoking (CERC-501: 16.5 min vs placebo: 17.7 min) or the number of cigarettes smoked (CERC-501: 3.3 cigarettes vs placebo: 3.1 cigarettes). Compared with placebo, CERC-501 also did not affect cigarette craving, mood, anxiety, nicotine withdrawal, or subjective effects of smoking. These findings do not support a role for CERC-501 in the treatment of nicotine use disorder. [ABSTRACT FROM AUTHOR]

Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they were willing-to-pay for various amounts of cigarettes and shop vouchers. Second, during functional magnetic resonance imaging, participants decided if they wanted to buy these cigarettes and vouchers for a set amount of money. We examined decision-making behaviour and brain activity when faced with cigarette and voucher decisions, purchasing (vs not purchasing) cigarettes and vouchers, and "value signals" where brain activity correlated with cigarette and voucher value. Dependent smokers had a higher willingness-to-pay for cigarettes and greater activity in the bilateral middle temporal gyrus when faced with cigarette decisions than occasional smokers. Across both groups, the decision to buy cigarettes was associated with activity in the left paracingulate gyrus, right nucleus accumbens, and left amygdala. The decision to buy vouchers was associated with activity in the left superior frontal gyrus, but dependent smokers showed weaker activity in the left posterior cingulate gyrus than occasional smokers. Across both groups, cigarette value signals were observed in the left striatum and ventromedial prefrontal cortex. To summarise, nicotine dependence was associated with greater behavioural valuation of cigarettes and brain activity during cigarette decisions. When purchasing cigarettes and vouchers, reward and decision-related brain regions were activated in both groups. For the first time, we identified value signals for cigarettes in the brain. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarette or e-cigarette are becoming popular in worldwide, including in Indonesia. Because e-cigarette is still relatively new in Indonesia, it needs to be determined the users' profile and e-cigarette use behavior and factors associated. Methods: A population based cross-sectional survey was employed. College and university including students age 16-24 years old were involved. The survey used proportionate quota sampling to obtain a representative sample of colleges in all five districts of Yogyakarta. The questionnaire was developed based on the Indonesian version of Global Youth Tobacco Survey. The descriptive analysis was used and we investigated association between characteristics with e-cigarette use using chi-square test. Results: About 920 respondents were participated in this study. About 98 (10.68%) were current e-cigarette user, about 530 (57.61%) were also experimental cigarette smokers. About 570 (61.96%) respondents were male with average aged 20.23 years old. Most of respondents (53.26%) had university level on their formal education. There were significant relationship between e-cigarette users and sociodemographic factors such as sex (OR 1.23-3.45), knowledge about smoking as harmful (OR 1.32-3.22), attitude toward smoking (OR 1.31- 3.15), cigarette smoking (OR 1.98-5.32) and alcohol consumption (OR 1.56-3.89). Conclusion: A subtantial number of e-cigarette users among teenage is potential problem for Indonesia. More research are needed to explore other characteristic and behavior of e-cigarette users so that the government can have the whole description of e-cigarette smokers in Indonesia. Restriction of e-cigarette comsumption is one of proposed strategies for better tobacco control in Indonesia. [ABSTRACT FROM AUTHOR]

Background: The prevalence of tobacco cigarette smoking in the US has declined to approximately 15%, yet, it remains over 90% among individuals with opioid use disorder regardless of whether they are currently using opioids illicitly or as opioid substitution therapy. This disparity raises the question of whether opioids facilitate smoking among individuals with opioid use disorder and whether opioid antagonists may reduce it.Objectives: Determine whether injectable extended-release naltrexone (XR-NTX) treatment of opioid use disorder patients is associated with a spontaneous smoking reduction. We hypothesized that treatment with XR-NTX for would lead to a reduction in smoking in tobacco cigarette smokers with opioid use disorder.Methods: We analyzed data from 64 tobacco cigarette smokers (38% female) with opioid use disorder who were induced on XR-NTX for prevention of relapse to opioids. The number of cigarettes smoked per day and opioid-related craving and withdrawal were assessed at baseline and during treatment.Results: Smoking was reduced from 14.4 ± 1.0 to 9.8 ± 1.0(p < 0.001) cigarettes per day after one month and 8.6 ± 1.1 cigarettes per day after two months of treatment. Daily cigarette consumption was positively correlated with the pre-treatment frequency of opioid use and opioid-related craving during the XR-NTX treatment.Conclusions: XR-NTX treatment in smokers with opioid use disorder was associated with a 29% decline in daily cigarette consumption. Together with prior evidence of increased smoking during opioid agonist therapy, our finding suggests a pharmacodynamic interaction between nicotine and opioid systems that could influence treatment choices in this population. Our findings merit confirmation in a prospective controlled study. (NCT02324725 and NCT01587196). [ABSTRACT FROM AUTHOR]

Background: Data are lacking on type of e-liquid vaped among e-cigarette users. Further, few studies assess all sources of nicotine used by e-cigarette users to assess whether poly-nicotine use relates to nicotine dependence (ND). The objectives were to describe young adult e-cigarette users by: (i) type of e-liquid vaped; (ii) poly-nicotine use; (iii) ND symptoms; and (iv) attempts to quit conventional cigarettes.Methods: Data were available in cycle 23 of a longitudinal investigation on the natural course of cigarette smoking and ND. A total of 775 young adults (44% male; mean (SD) age 30.5(1.0)) completed mailed self-report questionnaires in 2017-20.Results: Of 775 participants, 149 (19.2%) reported past-year e-cigarette use. Overall, 55.0% of e-cigarette users had used cannabis-containing e-liquid (31.5% vaped cannabis e-liquid exclusively); 50.4% used nicotine-containing e-liquid (23.5% vaped nicotine e-liquid exclusively); and 39.9% used e-liquid without nicotine (8.7% vaped e-liquid without nicotine exclusively). Most e-cigarette users (82.6%) used other nicotine-containing products including conventional cigarettes (72.5%); 60.8% reported ND symptoms, rising to 79.4% among those who vaped nicotine-containing e-liquid. Finally, 29.0% tried to quit conventional cigarettes using e-cigarettes in the past-year, but only 16.7% found them helpful.Conclusions: E-cigarettes now appear to appeal to a broader market than smokers who want to quit. More than half of young adult e-cigarette users vaped cannabis-containing e-liquid in the past year while only one-quarter had used e-cigarettes to assist with cessation. Most e-cigarette users used multiple nicotine-containing substances (including combustible cigarettes) which were associated with reports of ND symptoms. [ABSTRACT FROM AUTHOR]

Rationale: The smallest difference in nicotine that can change a smoker's cigarette preference is not clearly known. Objective: A procedure to efficiently identify the difference in nicotine needed to change cigarette preference could help inform research to gauge effects of a nicotine reduction policy. Methods: Using a within-subject design, we assessed preference for research cigarettes varying in nicotine contents (NIC; 18.7, 10.8, 5.3, 2.3, and 1.3 mg/g of tobacco), relative to a very low nicotine cigarette (VLNC; 0.4 mg/g), in 17 adult-dependent non-menthol smokers abstinent overnight. Only one NIC was compared vs. the VLNC per session, with order of the five NIC contents randomized across sessions on five separate days. Preference for each NIC vs. VLNC was determined by validated forced choice procedure, with those NIC chosen more than VLNC indicating greater reinforcement due to greater nicotine per se. Secondarily, less preference for lower NIC (vs. VLNC), relative to choice for the highest NIC, 18.7 mg/g (vs. VLNC), indexed reduced reinforcement. Results: Overall, NIC choices increased as their nicotine increased, as anticipated. Relative to the 0.4 mg/g VLNC, choice was greater for NIC ≥ 5.3 mg/g but not ≤ 2.3 mg/g. Correspondingly, relative to choice for 18.7 mg/g, choice was less for NIC ≤ 2.3 mg/g but not ≥ 5.3 mg/g. Conclusions: Although replication with larger samples and longer access is needed, results indicate that nicotine reduction to ≤ 2.3 mg/g in cigarettes would attenuate reinforcement. This choice procedure may efficiently inform future clinical trials to assess relative reinforcing effects of smoking reduced nicotine cigarettes. [ABSTRACT FROM AUTHOR]

Endothelial nitric oxide synthase (eNOS) malfunctioning has been proposed to contribute to the endothelial damage produced by cigarette. Besides eNOS, neuronal NOS (nNOS) is also expressed in most vascular tissues and plays an important role in the endothelium-dependent vascular relaxation. We hypothesize that nNOS may contribute to the endothelium dysfunction produced by cigarette in smokers. Vascular function was assessed in human resistance mesenteric arteries using a wire myograph, the level of protein expression by Western blot, eNOS and nNOS localization by immunofluorescence. Measurement of NO was assessed by fluorescence microscopy. Arteries of smokers showed impaired endothelium-dependent vascular relaxation in response to acetylcholine. Pharmacological nonselective blockade of NOS with l -NAME and selective nNOS blockade with inhibitor 1 reduced the relaxation of the mesenteric artery of both smokers and nonsmokers. Interestingly, the inhibitory effect of NOS inhibitors was greater in nonsmokers than in smokers. The expression of total nNOS and eNOS and the level of phosphorylation at eNOS-pSer1177 were reduced in arteries of smokers as compared with nonsmokers. No differences between groups were observed in the expression of total COX-1, COX-2, catalase and SOD-1. Immunofluorescence analysis showed the presence of nNOS in the vascular endothelium in both groups. Acetylcholine-induced NO production was impaired in arteries from smokers as compared to nonsmokers. Selective inhibition of nNOS caused a decreased in NO production, which was greater in nonsmokers than in smokers. Our data show that a decrease in nNOS expression contributes to the endothelial dysfunction caused by cigarette smoking in human. • The role of nNOS in endothelial dysfunction caused by cigarette smoking is unknown. • Chronic smoking causes NO impairment and endothelial dysfunction in human mesenteric arteries. • Chronic smoking decreases nNOS expression in human mesenteric arteries. • Decreased nNOS expression contributes to the endothelial dysfunction caused by smoking. [ABSTRACT FROM AUTHOR]

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen's effects in the resting brain can predict its effects during SC exposure. Methods: In this longitudinal, double blind, placebo-controlled neuropharmacological study 43 non-abstinent, sated treatment-seeking cigarette smokers (63% male) participated in an fMRI resting-state scan and a SC-reactivity task prior to (T1) and 3 weeks following randomization (T2; baclofen: 80 mg/day; n = 21). Subjective craving reports were acquired before and after SC exposure to explicitly examine SC-induced craving. Results: Whole-brain full-factorial analysis revealed a group-by-time interaction with greater resting brain activation of the right dorsolateral prefrontal cortex (dlPFC) at T2 in the baclofen group (BAC) (pFWEcorr = 0.02), which was associated with reduced neural responses to SCs in key cue-reactive brain regions; the anterior ventral insula and ventromedial prefrontal cortex (pFWEcorr < 0.01). BAC, but not the placebo group reported decreased SC-elicited craving (p = 0.02). Conclusion: Results suggest that baclofen mitigates the reward response to SCs through an increase in tonic activation of the dlPFC, an executive control region. Through these mechanisms, baclofen may offer SC-vulnerable smokers protection from SC-induced relapse. [ABSTRACT FROM AUTHOR]

Introduction: This 8-week multisite, randomized controlled trial of snus examined the differential effects of instructions on (1) snus use, (2) smoking and smoking-related measures, and (3) exposure to tobacco-related constituents.Method: US adult daily cigarette smokers (n = 150; 43.3% female; Medianage = 43.5) were recruited from Minneapolis, Minnesota; Columbus and Coshocton, Ohio; and Buffalo, New York. Following a 1-week sampling phase of snus, participants who used at least 7 pouches were randomized to either (1) partial substitution (PS; "use snus as you like with your cigarettes"), (2) complete substitution (CS; "avoid cigarettes"), or (3) usual brand cigarettes (UB). Analyses included between-group analyses (eg, PS vs. CS) using Wilcoxon rank sum test of cigarettes per day and snus pouches per day, and a linear mixed model (biomarkers).Results: Compared to the PS and UB groups, smokers assigned to CS reported greater reductions in cigarettes per day (ps < .001), using more snus pouches per day (p = .02), and more smoke-free days (CS median = 14.5, PS and UB medians = 0, p < .001). In addition, results demonstrated reductions in carbon monoxide (p < .001), total nicotine equivalents (p = .02), and four out of five measured volatile organic compounds (ps < .01) over time among the CS group. Exposure to N'-nitrosonornicotine increased by trial end only among the PS group (p < .04). Phenanthrene tetraol increased among all groups by trial end (p = .02) with no difference between groups.Conclusions: Instructions to completely switch from cigarettes to snus resulted in the greatest reduction in cigarettes and exposure to harmful constituents.Implications: Directly instructing smokers to switch completely to snus, rather than using ad libitum (with no instructions to avoid cigarettes), is necessary for reductions in smoking and subsequent exposure to harmful constituents. [ABSTRACT FROM AUTHOR]

Addiction to nicotine is extremely challenging to overcome, and the intense craving for the next cigarette often leads to relapse in smokers who wish to quit. To dampen the urges of craving and inhibit unwanted behaviour, smokers must harness cognitive control, which is itself impaired in addiction. It is likely that craving may interact with cognitive control, and the present study sought to test the specificity of such interactions. To this end, data from 24 smokers were gathered using EEG and behavioural measures in a craving session (following a three‐hour nicotine abstention period) and a non‐craving session (having just smoked). In both sessions, participants performed a task probing various facets of cognitive control (response inhibition, task switching and conflict processing). Results showed that craving smokers were less flexible with the implementation of cognitive control, with demands of task switching and incongruency yielding greater deficits under conditions of craving. Importantly, inhibitory control was not affected by craving, suggesting that the interactions of craving and cognitive control are selective. Together, these results provide evidence that smokers already exhibit specific control‐related deficits after brief nicotine deprivation. This disruption of cognitive control while craving may help to explain why abstinence is so difficult to maintain. [ABSTRACT FROM AUTHOR]