A Comparison of Mental Health Symptoms among Adults Who Vape Nicotine, Cannabis, or Both.

OBJECTIVES: Dual use of combustible cannabis and nicotine is related to worse mental health symptoms (MHS); however, little is known about MHS among those who vape cannabis and nicotine. The current study aimed to determine if dual use of cannabis and nicotine vapes is associated with worse MHS compared to single use and to identify correlates of MHS for dual users. METHODS: We used Amazon Mechanical Turk to survey adults (N = 492) who used nicotine or cannabis vapes in the past 30 days on stress, anxiety, depression, vape use behaviors and sociodemographic information. We conducted hierarchical linear regressions to compare MHS between dual vs. single substance vape use and to identify correlates of MHS, including sociodemographic variables and vape use characteristics. RESULTS: The final sample was 37.6% female, 87.6% White, and 11% Hispanic/Latinx with a mean age of 34.15 years. After controlling for sociodemographic characteristics and combustible product use, dual users had significantly higher mean MHS severity than single users. For dual users, younger age and being married were associated with higher symptoms of depression and stress. Holding a medical cannabis card was associated with higher anxiety symptoms. CONCLUSION: The findings suggest that dual use of cannabis and nicotine vapes is associated with worse MHS severity compared to single substance use.

Detection of DNA adducts derived from the tobacco carcinogens, benzo[a]pyrene and dibenzo[def,p]chrysene in human oral buccal cells.

Polycyclic aromatic hydrocarbons (PAHs) are recognized as potential etiological agents in the development of oral cancer in smokers. In particular, benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DB[a,l]P) are detected in cigarette smoke and the environment and can induce DNA damage, mutagenesis and carcinogenesis in the oral cavity of rodents. Consequently, DNA adducts are regarded as the most direct markers of genotoxicity and can be used as biomarkers of cancer risk. Thus, this study used LC-MS/MS analysis with isotope labeled internal standard to detect and quantify DNA adducts derived from B[a]P and DB[a,l]P in buccal cells of cigarette smokers and non-smokers. Participants in this study include 21 smokers and 16 non-smokers. Our data are the first to report that levels (mean ± SD) of BPDE-N2-dG were significantly (P < 0.001) higher in smokers (20.18 ± 8.40 adducts/108 dG) than in non-smokers (0.84 ± 1.02 adducts/108 dG). Likewise, levels of DBPDE-N6-dA in smokers (5.49 ± 3.41 adducts/108 dA) were significantly higher (P = 0.019) than non-smokers (2.76 ± 2.29 adducts/108 dA). Collectively, the results of this clinical study support that PAHs in tobacco smoke can contribute to the development of oral cancer in humans.

Nighttime Waking to Smoke, Stress, and Nicotine Addiction.

INTRODUCTION: Up to one-half of cigarette smokers may wake up during the night and smoke. This behavior may result in greater likelihood of cessation failure, clinically relevant sleep difficulties, and a range of health issues. Whereas the scientific literature has often attributed this behavior to nicotine dependence, up to 85% of smokers who wake at night and smoke attribute this behavior to factors other than nicotine. This study examines the relations between nicotine dependence, psychological distress, perceived stress, and waking at night to smoke. METHODS: A total of 351 adult smokers from the Pennsylvania Adult Smoking Study (PASS) completed self-report surveys and provided saliva for the evaluation of cotinine values. Survey instruments included measures of nicotine addiction, perceived stress, a broad measure of global psychological distress, and a range of demographic factors. RESULTS: Logistic regression demonstrated that nicotine addiction, psychological distress, and perceived stress were all related to waking at night to smoke, but cotinine levels were not. Mediation models found that psychological distress had a direct relation to waking at night to smoke, even when considering nicotine addiction and other causes of sleep disturbances (e.g., apnea and chronic physical pain). Alternative moderation and mediation models were conducted but did not support other plausible associations between variables. CONCLUSIONS: Waking at night to smoke is likely the result of both nicotine dependence and psychological distress. Given that cotinine levels were not associated with waking at night, the mechanisms of how nicotine dependence may affect waking at night need further investigation.

Intentions and Attempts to Quit JUUL E-Cigarette Use: The Role of Perceived Harm and Addiction.

INTRODUCTION: Research on electronic cigarette (e-cigarette) quit intentions and attempts is limited despite the potential health benefits of quitting, especially for long-term users. The current study aimed to investigate perceptions of harm and addictiveness and tobacco use characteristics associated with quit variables among users of a popular e-cigarette brand, JUUL. METHODS: We surveyed 301 US adult JUUL users on their tobacco use characteristics, perceptions of JUUL harm and addictiveness, and quit variables at 3 time points, from July 2019 to April 2020. We used logistic regression models to assess demographic characteristics, smoking characteristics, and perceptions of JUUL harm and addictiveness as correlates of e-cigarette quit intentions, attempts, importance, and confidence. RESULTS: Twenty-three percent of the sample had intentions to quit using JUUL within the year, and 22.6% reported making a lifetime quit attempt. The average rating of quit importance was 4.1 and quit confidence was 5.8 on a Likert scale of 1 to 10. More than 90% of the sample indicated that JUUL was at least moderately addictive, whereas less than one-quarter indicated that JUUL was as harmful or more harmful than smoking. Higher levels of perceived JUUL addictiveness were associated with more quit intentions, attempts, and importance. Higher levels of perceived JUUL harm compared with smoking were associated with more quit importance. CONCLUSION: Our findings suggest that a small proportion of adult JUUL users are interested in quitting. Self-reported perceptions of JUUL's addiction potential may be related to more quit attempts. Findings highlight the need for evidence-based information on e-cigarette addictiveness and effective strategies for cessation.

Switching to Progressively Reduced Nicotine Content Cigarettes in Smokers With Low Socioeconomic Status: A Double-Blind Randomized Clinical Trial.

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.

Characterizing nicotine exposure among a community sample of non-daily smokers in the United States.

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.

Clinical trial recruitment of adult African American smokers from economically disadvantaged urban communities.

This investigation evaluated the effectiveness and challenges of multiple recruitment methods, described as proactive, reactive, and combination methods, among adult African American smokers (N = 527) from economically disadvantaged urban communities enrolled to test progressively reduced nicotine content investigational cigarettes. The study evaluated success using descriptive statistics to measure the volume of phone calls and percentage of eligible participants per method. Reactive and combination strategies effectively prompted participants to call about the study. Combination methods yielded the highest eligibility rates. Findings demonstrate the unique recruitment successes within this population across a range of recruitment methods and may inform improved methods to recruit and engage African Americans in clinical trials.

A review of tobacco regulatory science research on vulnerable populations.

In 2013 the U.S. Food and Drug Administration and National Institutes of Health established fourteen Tobacco Centers of Regulatory Science (TCORS) to advance scientific knowledge relevant to conducting evidence-based tobacco regulation. This report reviews TCORS-funded research with adult vulnerable populations. The literature search included a list of all TCORS-funded publications compiled by the TCORS coordinating center; all TCORS were requested to share publications not in the coordinating-center's list. Only TCORS-funded reports describing an empirical study with an adult vulnerable population published in a peer-reviewed journal between September 2013 and June 2018 were included. 71 reports met inclusion criteria; 39% (28/71) examined tobacco use among those with mental health and medical comorbidities, 34% (24/71) socioeconomic disadvantage, 31% (22/71) women of reproductive age, 30% (21/71) racial/ethnic minorities, 18% (13/71) rural residents, and 3% (2/71) each among active military/veterans and sexual/gender minorities. Regarding scientific domains, 63% (45/71) investigated behavior, 37% (26/71) addiction, 24% (17/71) health effects, 20% (14/71) impact analyses, 18% (13/71) toxicity, 8% (6/71) marketing influences, and 7% (5/71) communications. Totals exceed 100% because some reports addressed multiple populations/domains. TCORS funding has generated a substantial, multidisciplinary body of new scientific knowledge on tobacco use in adult vulnerable populations. However, considerable variability was noted in the amount of research conducted across the various vulnerable populations and scientific domains. Most notably, relatively few studies focused on active military/veterans or sexual/gender minorities, and the scientific domains of marketing influences and communications were conspicuously underrepresented. These are important knowledge gaps to address going forward.

Characteristics of Adult Cigarette Smokers Who "Relight" and the Effects of Exposure to Tobacco Smoke Constituents.

INTRODUCTION: About half of smokers relight their cigarette, a habit that is a risk factor for chronic bronchitis and possibly lung cancer. Little is known about the characteristics of smokers who relight and their dependence on nicotine. It is unknown whether relighting affects exposure to tobacco smoke constituents. This study examined the characteristics of relighters of usual brand cigarettes and whether relighting affects exposure to selected tobacco smoke constituents. METHODS: We explored relighting status and frequency, using baseline data from 248 adult smokers participating in studies of reduced nicotine cigarettes in relation to demographic and cigarette characteristics, smoking behaviors, nicotine dependence, biomarkers of exposure (exhaled carbon monoxide, blood cotinine), and biomarkers of oxidative stress (ratio of oxidized/reduced glutathione). RESULTS: 69.4% (n = 172) of subjects reported relighting, and they relit an average of five cigarettes out of 20. Both relighters and non-relighters smoked a mean of 20 cigarettes per day (p = .6). Relighting was significantly associated with higher nicotine dependence, use of longer rod cigarettes, older age, lower income, and unemployment. There were no significant associations between relighting and blood cotinine, exhaled carbon monoxide or measures of oxidized/reduced blood glutathione. CONCLUSIONS: The majority of subjects were relighters, who had higher levels of nicotine dependence than non-relighters. Relighters had similar levels of plasma cotinine and exhaled carbon monoxide to non-relighters. IMPLICATIONS: No study has compared the cigarette characteristics and biomarkers of exposure of adult cigarette smokers who relight with those who do not. Relighting behavior was common in our sample and was associated with low income, not currently working, higher nicotine dependence, cigarette rod length, daily cigarette use years, and a lifetime history of depressed mood.

Socioeconomic differences in nicotine exposure and dependence in adult daily smokers.

BACKGROUND: Socioeconomic status (SES) is a major determinant of tobacco use but little is known whether SES affects nicotine exposure and the degree of nicotine dependence. METHODS: The Pennsylvania Adult Smoking Study is a cross-sectional study of smoke exposure and nicotine dependence among adults conducted in central Pennsylvania between June 2012 and April 2014. The study included several measures of SES, including assessments of education and household income, as well as occupation, home ownership, health insurance, household density and savings accounts. Measurements included saliva for the nicotine metabolites cotinine (COT), 3-'hydroxycotinine (3HC) and total metabolites (COT +3HC). Puffing behavior was determined using portable smoking topography devices. RESULTS: The income levels of lighter smokers (< 20 cigarettes per day) was $10,000 more than heavier smokers. Higher Fagerström Test for Nicotine Dependence scores were associated with lower income and job status, scores ranged from 5.4 in unemployed, 4.4 in blue-collar, and 3.8 in white-collar workers. In principal components analysis used to derive SES indicators, household income, number in household, and type of dwelling were the major SES correlates of the primary component. Job category was the major correlate of the second component. Lower SES predicted significantly higher adjusted total nicotine metabolite levels in the unemployed group. Job category was significantly associated with total daily puffs, with the highest level in the unemployed, followed by blue-collar workers, after adjustment for income. CONCLUSIONS: Among smokers, there was a relationship between lower SES and increased nicotine dependence, cigarettes per day and nicotine exposure, which varied by job type.

Ecological momentary assessment of smoking behaviors in native and converted intermittent smokers.

BACKGROUND AND OBJECTIVES: About 22% of adult smokers in the U.S. are intermittent cigarette smokers (ITS). ITS can be further classified as native ITS who never smoked daily and converted ITS who formerly smoked daily but reduced to intermittent smoking. Ecological momentary assessment (EMA) was conducted to determine the behaviors and experiences that are associated with the decision to smoke. METHODS: The study included 24 native ITS and 36 converted ITS (N = 60) from the Pennsylvania Adult Smoking Study. A baseline questionnaire, daily log, and an EMA smoking log that assessed emotions, activities, and smoking urges was filled out with each cigarette for 1 week to capture 574 smoking sessions. RESULTS: Both groups had very low levels of cigarette dependence. Both groups were more tempted to smoke in positive or negative situations than situations associated with habituation. EMA showed that the most common emotional state during smoking sessions was positive (47%), followed by negative (32%), neutral (16%), and mixed (5%) emotions. Smokers were more likely to smoke during activities of leisure (48%) than during performative duties (29%), social (16%) or interactive occasions (7%). Converted ITS were more likely to smoke alone compared to native ITS (p < .001). DISCUSSION AND CONCLUSIONS: ITS report minimal levels of dependence when captured on traditional scales of nicotine dependence, yet experience loss of autonomy and difficulty quitting. The majority of the ITS reported positive emotions and leisure activities while smoking, and smoked during the evening. SCIENTIFIC SIGNIFICANCE: The current paper identifies environmental and behavioral factors that are associated with smoking among ITS in real time. (Am J Addict 2018;27:131-138).

A two-site, two-arm, 34-week, double-blind, parallel-group, randomized controlled trial of reduced nicotine cigarettes in smokers with mood and/or anxiety disorders: trial design and protocol.

BACKGROUND: The U.S. Food and Drug Administration can set standards for cigarettes that could include reducing their nicotine content. Such a standard should improve public health without causing unintended serious consequences for sub-populations. This study evaluates the effect of progressive nicotine reduction in cigarettes on smoking behavior, toxicant exposure, and psychiatric symptoms in smokers with comorbid mood and/or anxiety disorders using a two-site, two-arm, double-blind, parallel group, randomized controlled trial (RCT) in four phases over 34 weeks. METHODS: Adult smokers (N = 200) of 5 or more cigarettes per day will be randomized across two sites (Penn State and Massachusetts General). Participants must have not had a quit attempt in the prior month, nor be planning to quit in the next 6 months, meet criteria for a current or lifetime unipolar mood and/or anxiety disorder based on the structured Mini-International Neuropsychiatric Interview, and must not have an unstable medical or psychiatric condition. After a week of smoking their own cigarettes, participants receive two weeks of Spectrum research cigarettes with usual nicotine content (11.6 mg). After this baseline period, participants will be randomly assigned to continue smoking Spectrum research cigarettes that contain either (a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in five steps over 18 weeks. At the end of the randomization phase, participants will be offered the choice to either (a) quit smoking with assistance, (b) continue smoking free research cigarettes, or (c) return to purchasing their own cigarettes, for the final 12 weeks of the study. The primary outcome measure is blood cotinine; key secondary outcomes are: exhaled carbon monoxide, urinary total NNAL- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 1-hydroxypyrene, oxidative stress biomarkers including 8-isoprostanes, measures of psychiatric symptoms (e.g., depression, anxiety), smoking behavior and dependence (e.g., cigarette consumption, quit attempts), and health effects (e.g., blood pressure, respiratory symptoms). DISCUSSION: Results from this study will inform FDA on the potential effects of regulating the nicotine content of cigarettes and help determine whether smokers with mood and/or anxiety disorders can safely transition to significantly reduced nicotine content cigarettes. TRIAL REGISTRATION: TRN: NCT01928758 , registered August 21, 2013.

Comparison of Puff Volume With Cigarettes per Day in Predicting Nicotine Uptake Among Daily Smokers.

The role of inhalation behaviors as predictors of nicotine uptake was examined in the Pennsylvania Adult Smoking Study (2012-2014), a study of 332 adults whose cigarette smoking was measured in a naturalistic environment (e.g., at home) with portable handheld topography devices. Piecewise regression analyses showed that levels of salivary cotinine, trans-3'-hydroxycotinine, and total salivary nicotine metabolites (cotinine + trans-3'-hydroxycotinine) increased linearly up to a level of about 1 pack per day (20 cigarettes per day (CPD)) (P < 0.01). Total daily puff volume (TDPV; in mL) (P < 0.05) and total daily number of puffs (P < 0.05), but not other topographical measures, increased linearly with CPD up to a level of about 1 pack per day. The mean level of cotinine per cigarette did not change above 20 CPD and was 36% lower in heavy smokers (≥20 CPD) than in lighter smokers (<20 CPD) (15.6 ng/mL vs. 24.5 ng/mL, respectively; P < 0.01). Mediation models showed that TDPV accounted for 43%-63% of the association between CPD and nicotine metabolites for smokers of <20 CPD. TDPV was the best predictor of nicotine metabolite levels in light-to-moderate smokers (1-19 CPD). In contrast, neither CPD, total daily number of puffs, nor TDPV predicted nicotine metabolite levels above 20 CPD (up to 40 CPD). Finally, although light smokers are traditionally considered less dependent on nicotine, these findings suggest that they are exposed to more nicotine per cigarette than are heavy smokers due to more frequent, intensive puffing.

The Effects of Black Raspberry as a Whole Food-Based Approach on Biomarkers of Oxidative Stress in Buccal Cells and Urine of Smokers.

Cigarette smoke is a rich source of free radicals that can promote oxidative stress and carcinogenesis, including head and neck squamous cell carcinoma (HNSCC) development; importantly, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-iso-prostaglandin F2α (8-isoprostane) are biomarkers of oxidative stress. Several mechanisms, including the antioxidant properties of black raspberry (BRB), account for their chemopreventive effects. In the present clinical trial, we tested the hypothesis that BRB administration reduces biomarkers levels of oxidative stress in buccal cells and urine of smokers. One week after enrolling 21 smokers, baseline buccal cells and urine samples were collected before the administration of BRB lozenges for 8 weeks (5/day, 1 gm BRB/lozenge). Buccal cells and urine samples were collected at the middle and the end of BRB administration. The last samples were collected after the BRB cessation (washout period). We analyzed levels of 8-oxodG and 8-isoprostane (LC/MS-MS), urinary cotinine (ELISA), and creatinine (spectrophotometry). BRB significantly reduced the levels of 8-oxodG by 17.08% (P = 0.00079) in buccal cells and 12.44% (P = 0.034) in urine at the middle of BRB administration as compared with baseline; the corresponding values at the end of BRB administration were 16.46% (P = 0.026) in buccal cells and 25.72% (P = 0.202) in urine. BRB had no significant effect on the levels of urinary 8-isoprostane. BRB's capacity to inhibit 8-oxodG formation of smokers' buccal cells and urine is clearly evident and the reduction in 8-oxodG suggests that antioxidant abilities are central to BRB's HNSCC chemopreventive properties. PREVENTION RELEVANCE: Cigarette smoke contains highly active components namely free radicals that can promote oxidative stress and oral cancer. We found that black raspberry (BRB) inhibited the formation of oxidative stress markers in the oral cavity and urine of smokers suggesting the antioxidant abilities of BRB in preventing oral cancer.

A Comparison of Vaping Behavior, Perceptions, and Dependence among Individuals Who Vape Nicotine, Cannabis, or Both.

Background: Electronic delivery systems (e.g., vapes, e-cigarettes) are now popular modes of cannabis and nicotine administration that are often used by the same individuals; however, we still know little about dual nicotine and cannabis vaping. Materials & Methods: An online convenience sample of adult nicotine and/or cannabis vape users residing in the United States completed a 60 min survey on sociodemographic characteristics, cannabis and/or nicotine vape use behaviors and dependence, reasons for vape use, and perceptions of benefits and harms. After data cleaning, we compared dual vs. nicotine-only and cannabis-only vape users with univariate statistics and step-wise hierarchical linear regression analyses. Additionally, we assessed the factor structure, internal consistency, and criterion and convergent validity of the Penn State Cannabis Vaping Dependence Index (PSCVDI). Results: The final sample included 357 dual, 40 cannabis, and 106 nicotine vape users. Compared to nicotine- and cannabis-only vapers, dual vapers started using their nicotine and cannabis vapes at a younger age (p < 0.001), used them for more years (p < 0.001), and were less likely to use their nicotine vape to replace combustible cigarettes (p = 0.047). Dual users vs. single-substance users did not have significantly higher nicotine or cannabis vape dependence scores after controlling for sociodemographic and use behaviors. The PSCVDI showed adequate validity for measuring cannabis vape dependence. Conclusions: This survey is the first to highlight important differences in vape use behaviors and reasons for use between dual vs. cannabis- and nicotine-only vape users.

Effect of menthol on nicotine reduction: Pooled results from two double-blind randomized controlled trials.

BACKGROUND: Menthol upregulates nicotinic acetylcholine receptors and is associated with tobacco dependence. The effects of menthol when smoking cigarettes with varying low nicotine content up to 98 % (e.g., non-addicting) less than commercial cigarettes is not well understood. The U.S. Food and Drug Administration is considering two tobacco product standards in cigarettes including banning menthol and reducing nicotine content. These new standards have the potential to significantly reduce smoking initiation and maintenance by limiting the mechanistic effects of nicotine and menthol on the brain. METHODS: We conducted two parallel randomized clinical trials of gradually reduced nicotine in cigarettes from 11.6 mg down to 0.2 mg nicotine/cigarette (very low nicotine content; VLNC) vs. usual nicotine content (11.6 mg; UNC) over an 18-week period in people who smoke cigarettes with low socioeconomic status (SES) and mental health conditions. RESULTS: Compared to UNC, VLNC was associated with significant reductions in cotinine, cigarettes per day, expired carbon monoxide levels, nicotine dependence and symptomology. These associations did not differ between menthol and non-menthol cigarettes, except people who smoke menthol cigarettes had less of a cotinine reduction in the SES trial. The pooled odds ratio of being adherent with using only VLNC study cigarettes in the gradual nicotine reduction arm for people who smoke non-menthol vs. menthol cigarettes was 2.6 (95 % CI:1.0, 6.4; p-value: 0.04). CONCLUSIONS: When nicotine is lowered to non-addicting levels, the results indicate an independent effect of menthol on the need to sustain nicotine intake in addicted people who smoke cigarettes.

The effects of reduced nicotine content cigarettes on biomarkers of nicotine and toxicant exposure, smoking behavior and psychiatric symptoms in smokers with mood or anxiety disorders: A double-blind randomized trial.

BACKGROUND: The U.S. Food and Drug Administration and the government of New Zealand have proposed a reduction of the nicotine content in cigarettes to very low levels. This study examined the potential effects of this regulation in smokers with affective disorders. METHODS: In a randomized controlled parallel group trial conducted at two sites in the USA (Penn State University, Hershey, PA and Massachusetts General Hospital, Boston, MA) 188 adult smokers with a current (n = 118) or lifetime (n = 70) anxiety or unipolar mood disorder, not planning to quit in the next 6 months, were randomly assigned (1:1) to smoke either Usual Nicotine Content (UNC) (11.6 mg nicotine/cigarette) research cigarettes, or Reduced Nicotine Content (RNC) research cigarettes where the nicotine content per cigarette was progressively reduced to 0.2 mg in five steps over 18 weeks. Participants were then offered the choice to either receive assistance to quit smoking, receive free research cigarettes, or resume using their own cigarette brand during a 12-week follow-up period. Main outcomes were biomarkers of nicotine and toxicant exposure, smoking behavior and dependence and severity of psychiatric symptoms. The pre-registered primary outcome was plasma cotinine. RESULTS: A total of 143 (76.1%) randomized participants completed the randomized phase of the trial, 69 (73.4%) in the RNC group and 74 (78.8%) in the UNC group. After switching to the lowest nicotine content cigarettes, compared to smokers in the UNC group, at the last randomized visit the RNC group had significantly lower plasma cotinine (metabolite of nicotine): difference between groups, -175.7, 95% CI [-218.3, -133.1] ng/ml. Urine NNAL (metabolite of NNK, a lung carcinogen), exhaled carbon-monoxide, cigarette consumption, and cigarette dependence were also significantly lower in the RNC group than the UNC group. No between-group differences were found on a range of other biomarkers (e.g. 8-isoprostanes) or health indicators (e.g. blood pressure), or on 5 different psychiatric questionnaires, including the Kessler K6 measure of psychological distress. At the end of the subsequent 12-week treatment choice phase, those randomized to the RNC group were more likely to have quit smoking, based on initial intent-to-treat sample, n = 188 (18.1% RNC v 4.3% UNC, p = 0.004). CONCLUSION: Reducing nicotine content in cigarettes to very low levels reduces some toxicant exposures and cigarette addiction and increases smoking cessation in smokers with mood and/or anxiety disorders, without worsening mental health. TRIAL REGISTRATION: TRN: NCT01928758, registered August 21, 2013.

Changes in salivary proteome before and after cigarette smoking in smokers compared to sham smoking in nonsmokers: A pilot study.

INTRODUCTION: Smoking is the leading cause of preventable disease. Although smoking results in an acute effect of relaxation and positive mood through dopamine release, smoking is thought to increase stress symptoms such as heart rate and blood pressure from nicotine-induced effects on the HPA axis and increased cortisol. Despite the importance in understanding the mechanisms in smoking maintenance, little is known about the overall protein and physiological response to smoking. There may be multiple functions involved that if identified might help in improving methods for behavioral and pharmacological interventions. Therefore, our goal for this pilot study was to identify proteins in the saliva that change in response to an acute smoking event versus acute sham smoking event in smokers and non-smokers, respectively. METHODS: We employed the iTRAQ technique followed by Mass Spectrometry to identify differentially expressed proteins in saliva of smokers and non-smokers after smoking cigarettes and sham smoking, respectively. We also validated some of the salivary proteins by ELISA or western blotting. In addition, salivary cortisol and salivary amylase (sAA) activity were measured. RESULTS: In all, 484 salivary proteins were identified. Several proteins were elevated as well as decreased in smokers compared to non-smokers. Among these were proteins associated with stress response including fibrinogen alpha, cystatin A and sAA. Our investigation also highlights methodological considerations in study design, sampling and iTRAQ analysis. CONCLUSIONS: We suggest further investigation of other differentially expressed proteins in this study including ACBP, A2ML1, APOA4, BPIB1, BPIA2, CAH1, CAH6, CYTA, DSG1, EST1, GRP78, GSTO1, sAA, SAP, STAT, TCO1, and TGM3 that might assist in improving methods for behavioral and pharmacological interventions for smokers.

COVID-19 Vaccination Uptake and Hesitancy Among Current Tobacco Users.

Novel mRNA vaccines have been developed and were first distributed to high-risk individuals (including smokers) in the United States starting in December 2020 to combat the coronavirus (COVID-19) pandemic. Over one-half of the U.S. adult population has received at least 1 dose of a COVID-19 vaccine, but many others have reported hesitation about becoming vaccinated. We examined COVID-19 vaccine uptake and hesitancy from a convenience sample of Pennsylvanian adult smokers in April 2021, approximately 3 months after tobacco users were eligible to receive vaccination in the state. Participants (n = 231) were 23.4% male, 90.5% white, and had a mean age of 48.1 (SD = 11.9) years. All participants were current tobacco users, with the majority reporting current cigarette smoking (90.9%) with an average of 16 (SD = 8.1) cigarettes smoked per day. Nearly 60% (n = 137) reported receiving at least 1 dose of the vaccine and of those who did not (n = 94), 84% (n = 79) said they were somewhat or very unlikely to get a vaccine. Those who were unvaccinated were more likely to not consume news about COVID-19 (chi-square P-value < .01) and less likely to believe government news sources as reliable information for COVID-19 (chi-square P-value < .01). Qualitative responses among those who were vaccine hesitant expressed concerns about the lack of research on the vaccine, distrust of the safety of the vaccine, and fears about side effects. Understanding vaccine hesitancy among tobacco users can help develop targeted communication strategies and directly address concerns to promote vaccination among this population who may be at an increased risk of severe complications from COVID-19.

Tobacco Use Changes and Perceived Health Risks among Current Tobacco Users during the COVID-19 Pandemic.

COVID-19 has become a global pandemic, with over 81 million cases worldwide. To assess changes in tobacco use as a result of the pandemic, we surveyed a convenience sample of current tobacco users between April and June 2020. The sample was taken from a tobacco user research registry (n = 3396) from the Penn State College of Medicine in Hershey, Pennsylvania, USA. Participants who responded to the survey and were eligible for this study (n = 291) were 25.6% male, 93% white, and had a mean age of 47.3 (SD = 11.6) years. There were no reports of participants testing positive for COVID-19, but 21.7% reported experiencing symptoms associated with the virus. Most participants (67%) believed that their risk of contracting COVID-19 was the same as non-tobacco users, but 57.7% believed that their risk of serious complications, if infected, was greater compared to non-tobacco users. A total of 28% reported increasing their cigarette use during the pandemic. The most common reasons for increased use were increased stress, more time at home, and boredom while quarantined. Nearly 15% reported decreasing their tobacco use. The most common reasons for reduced use were health concerns and more time around non-smokers (including children). A total of 71 (24.5%) users reported making a quit attempt. Characterizing these pandemic-related changes in tobacco use may be important to understanding the full scope of subsequent health outcomes resulting from the pandemic. Tobacco cessation resources should be tailored to allow for safe, appropriate access for those interested in quitting.