Nicotine Levels Research Articles

EL HÁBITO DE FUMAR Y SU INFLUENCIA EN LA CONSOLIDACIÓN ÓSEA: UNA REVISIÓN INTEGRADORA

Smoking is considered one of the risk factors for various diseases, not only related to the respiratory system but also influencing the physiological processes of various organs and body systems. This article aims to deepen the understanding of the effects of smoking on bone healing by analyzing its molecular, cellular, and clinical bases. This process is subject to possible direct or indirect interferences from chemical substances such as nicotine. It is important to note that, besides conventional cigarettes, there is also indiscriminate use of electronic cigarettes, which, according to an analysis conducted by Pérez and Duarte (2022), have considerably higher nicotine levels than traditional cigarettes. Another study conducted by González et al. (2021) highlights the increasing popularity of these devices among young people, underscoring the importance of preventive measures. According to the National Institute of Traumatology and Orthopedics (INTO), inhaling tobacco smoke increases bone tissue healing time by 60%, thus delaying the body's ability to heal injuries and compromising bone absorption. The clinical repercussions of smoking on the quality and speed of bone recovery after fractures and orthopedic procedures are identified to improve understanding and develop specific clinical strategies and interventions for smoking patients. The specific objectives of this research were to: investigate the molecular and cellular mechanisms of the bone healing process, analyze the effects of smoking on the quality of the formed tissue, evaluate the influence of smoking on the bone healing time in patients after fracture or orthopedic surgery, and finally propose therapeutic strategies and preventive measures to improve bone healing. To this end, a bibliographic search was conducted on articles relevant to the topic using various means. The selection of articles was based on three stages, choosing those that met the inclusion criteria. During the development of this article, it is observed that smoking is an extended and ancestral practice, being a constant and emerging health problem. Additionally, it is considered a modifiable risk factor for decreasing bone density. In conclusion, the need for specific strategies to address complications in bone healing in smoking patients is highlighted.

Total and unprotonated (freebase) nicotine content in new types of oral ‘tobacco-free’ nicotine products

SignificanceNicotine-containing products, labelled as being ‘tobacco-free’ nicotine (TFN), are marketed to consumers as alternatives to conventional tobacco products. Little is known about these emerging products and their contents.MethodsMoisture, total nicotine...

Beyond smoking: Risk assessment of nicotine in pouches

Orally consumed nicotine pouches that contain no tobacco are marketed as a less harmful alternative to tobacco products. This study aims to assess nicotine in pouches and potential risks for health damage. 31 samples of nicotine pouches were collected and analyzed. The median nicotine uptake from single pouches was calculated to be 65 µg/kg bw. Consumption of more than one pouch per day would lead to a strikingly higher nicotine dose over the day. Health effects after nicotine exposure are, among others, cardiovascular effects. An acute reference dose (ARfD) of 0.8 µg/kg bw was proposed for risk assessment purposes based on an observed increased heart rate in a human study after acute nicotine uptake. The ARfD was exceeded by at least 20-fold, even when considering the consumption of a single pouch with the lowest detected nicotine level. With higher nicotine contents in pouches or with an increasing number of pouches per day, vast ARfD exceedances are possible. Therefore, a clinically relevant elevation of heart rate is very likely to occur in consumers after acute consumption of nicotine pouches.

Desorption efficiency and holding capacity of acid-treated filters for nicotine sampling in vape shops.

Efficient sampling materials are essential for assessing nicotine levels in vape shops and other settings where nicotine exposures may exist. Two different treatments of Whatman glass fiber type A (GF/A) filters (sodium bisulfate treated and citric acid treated) were evaluated for nicotine capture, desorption efficiency, and holding capacity using Gas Chromatography-Mass Spectrometry (GC-MS). The Filters were treated with 0.8mL of 0.1 M sodium bisulfate or citric acid solution and oven-dried (80 °C) for 30min. Nicotine was desorbed off the filters using a modified analytical method. The average nicotine desorption efficiency for sodium bisulfate-treated GF/A filters (98.4%) was significantly higher than that of citric acid-treated GF/A filters (60.9%) over a range of 1-100 µg nicotine. Sodium bisulfate-treated and citric acid-treated GF/A filters experienced a 10% nicotine breakthrough after being dosed with about 550 and 2,750 µg of nicotine, respectively compared to 75 µg for untreated GF/A filters. Citric acid-treated GF/A filters had a much greater nicotine-holding capacity, but nicotine desorption from citric acid-treated GF/A filters was below the recommended criteria. Therefore, we recommend that sodium bisulfate-treated GF/A filters are employed for sample of nicotine with the GC-MS method.

Biomarkers of Nicotine and Toxicant Exposure by E-liquid Nicotine Concentration Level among U.S. Adult Exclusive E-cigarette Users.

The current e-cigarette market has been rapidly evolving with an increase in the share of high nicotine concentration vaping products. This study examined urinary biomarkers of exposure (BOEs) by nicotine concentration level among exclusive e-cigarette users. Data were drawn from Wave 5 (December 2018-November 2019) of the Population Assessment of Tobacco and Health (PATH) Study. Between-subject differences in BOEs of nicotine, metal, tobacco-specific nitrosamine (TSNA), and volatile organic compounds (VOC) were examined across e-cigarettes containing nicotine or not (yes [n=300] vs. no [n=31] vs. non-tobacco use [n=3021]) and different nicotine concentration levels (0.1-1.7%, 1.8-4.9%, and 5.0%+). Among 3353 participants, exclusive e-cigarette users exhibited higher mean concentrations of nicotine metabolites than non-tobacco users. Nicotine e-cigarette users had higher concentrations of TNE2 (mean [95% CI]=21.8 [15.2-31.2] vs. 0.2 [0.1-0.6] nmol/mg creatinine, p<.0001) and cotinine (1418.2 [998.0-2015.4] vs. 12.2 [0.1-0.6], p<.0001) ng/mg creatinine, p<.0001) than non-nicotine e-cigarette users. Users of e-cigarette products with nicotine levels of 1.8-4.9% had higher TNE2 and cotinine levels than those using 0.1-1.7%, though differences were insignificant after adjusting for covariates. As compared to non-tobacco users, nicotine vapers had higher concentrations of lead (adjusted p=0.01). Nicotine containing e-cigarette users exhibited elevated levels of nicotine metabolites than non-nicotine containing vapers and non-tobacco users. Future research needs to investigate health effects of e-cigarette use across different nicotine levels Impact: Regulating the nicotine content in e-cigarettes could be crucial in managing nicotine exposure and potentially mitigating associated health risks.

Addiction among high school students: determination of nicotine, substance, game, and internet addiction levels

ABSTRACT Aim The aims of this study were to determine the levels of cigarette smoking, psychoactive substances, game, and internet addiction among high school students and to examine whether addictions show a significant difference according to some socio-demographic variables and the relationships between addiction types. Method A total of 530 high school students studying in Turkey, agreed to participate in the study. Data were collected through face-to-face interviews using the Sociodemographic Questionnaire (which contains DSM-V categories of addictive substances), Fagerström Test for Nicotine Dependence (FTND), Game Addiction Scale (GAS), and Internet Addiction Test (IAT). Results Approximately 1.9% of the respondents were smokers and 0.8% were inhalant users. Respondents scored 7.43 ± 2.88 on FTND, 13.92 ± 5.57 on the GAS, and 43.44 ± 18.80 on the IAT. Male respondents received a higher average score on the GAS than female respondents, and female respondents received a higher average score on the IAT than male respondents. As body mass index increased, a statistically significant, positive and moderate correlation was found between GAS scores and IAT scores. Conclusion Addictions are becoming more and more widespread and measures, information, and research should be increased and young people should be educated about addictions.

Effect of nicotine mouth spray on urges to vape: A randomized, placebo-controlled, pharmacodynamic clinical trial in exclusive e-cigarette users.

To determine whether nicotine mouth spray provides rapid and prolonged relief of urges to vape and measure the steady-state plasma nicotine levels during vaping and ad libitum mouth spray usage in e-cigarette users. Randomized, parallel group, double-blind trial. Single site at Hammersmith Medicines Research Ltd (HMR), London, UK. 216 (25.9% females, average age 27.6±7.63 [standard deviation, SD]) exclusive vapers who used their e-cigarette within 30 minutes of waking up and had vaped about 2years on average. Two sprays of 1mg nicotine mouth spray (Nicorette QuickMist Freshmint, n = 109), or placebo (identical in appearance and presentation, n = 107). Urge to vape was rated on a 100 mm visual analogue scale before and repeatedly for 2hours after administration. The primary outcome measured average change from baseline in urges to vape ratings during the first hour. Nicotine mouth spray achieved statistically significantly greater reductions in urges to vape than placebo from the first assessment point at 30 seconds to 1hour, when the estimated mean treatment difference was 11.90 mm (95% confidence interval [CI] = 6.86-16.95, P < 0.001). The integrated urge to vape over 11 hours ad libitum usage showed a statistically significant benefit compared with placebo (2.00 [0.88 SD] vs 2.51 [0.84 SD], P< 0.001). Mean steady-state plasma nicotine concentrations were lower after nicotine mouth spray usage compared with vaping (6.22 [4.70 SD] ng/ml vs 9.91 [7.59 SD] ng/ml, respectively). Adverse events were more commonly reported in the nicotine mouth spray group and were mostly mild. Among regular e-cigarette users, nicotine mouth spray provided statistically significant and fast relief of urges to vape one hour after dosing. Nicotine mouth spray showed statistically significant reductions in urges to vape as soon as 30 seconds and up to 2hours after dosing compared with placebo, and nicotine mouth spray was well-tolerated and safe.

Enhanced lipid production of Auxenochlorella pyrenoidosa using biochar-pretreated tobacco industry wastewater

Tobacco industry wastewater, containing high levels of nicotine, organic carbon, dyes, and other pollutants, presents significant environmental and health challenges. This study evaluates the combined application of wood-derived biochar and microalgal biorefineries for effective treatment of this wastewater. A 3 % biochar dosage was determined to be optimal, achieving complete nicotine removal, enhancing wastewater transmittance from 12.29 % to 88.8 %, and reducing chemical oxygen demand (COD) levels by 87.7 % to 1757.3 mg/L, creating conditions favorable for the growth of Auxenochlorella pyrenoidosa. The pretreatment preserved key nutrients, such as sugars, total nitrogen (TN), and total phosphorus (TP), which supported enhanced microalgal photosynthesis and led to significant increases in biomass and lipid accumulation, particularly in unsaturated fatty acids. This shift in lipid composition contributed to a significant reduction in the cold filter plugging point value, improving the suitability of microalgae-derived biodiesel for use in cold climates. Transcriptomic analysis revealed upregulation of pathways involved in photosynthesis, carbon fixation, and fatty acid biosynthesis, while downregulation of the tricarboxylic acid (TCA) cycle minimized acetyl-CoA consumption, further promoting lipid synthesis. This integrated approach not only effectively detoxifies tobacco industry wastewater but also converts it into valuable biofuels, offering a promising and sustainable strategy for waste management and biofuel production.

Pharmacokinetic Analysis of Nicotine and Its Metabolites (Cotinine and trans-3'-Hydroxycotinine) in Male Sprague-Dawley Rats Following Nose-Only Inhalation, Oral Gavage, and Intravenous Infusion of Nicotine.

Nicotine is an alkaloid found in tobacco. Human exposure to nicotine primarily occurs through the use of tobacco products. To date, limited nicotine pharmacokinetic data in animals have been reported. This study exposed male Sprague-Dawley rats to vehicle (and/or air) or four doses of nicotine via nose-only inhalation (INH), oral gavage (PO), and intravenous (IV) infusion. Plasma, six tissues (brain, heart, lung, liver, kidney, and muscle), and urine were collected at multiple timepoints from 5 minutes to 48 hours post-dose. The concentrations of nicotine, cotinine, and trans-3'-hydroxycotinine (3-OH-cotinine) were determined, and the pharmacokinetic profiles were compared among the four doses for each route. The results indicated that after single nicotine dose, nicotine bioavailability was 53% via PO. Across all the administration routes and doses, nicotine was quickly distributed to all six tissues; kidney had the highest nicotine and cotinine levels, and the lung had the highest 3-OH-cotinine levels; nicotine was metabolized extensively to cotinine and cotinine was metabolized to a lesser extent to 3-OH-cotinine; the elimination of plasma nicotine, cotinine, and 3-OH-cotinine followed first-order kinetics; plasma nicotine had a shorter half-life than cotinine or 3-OH-cotinine; the half-lives of plasma nicotine, cotinine, and 3-OH-cotinine were dose- and route-independent; and nicotine and cotinine were major urinary excretions followed by 3-OH-cotinine. Nicotine, cotinine, and 3-OH-cotinine levels in plasma, tissues, and urine exhibited dose-dependent increases. These study findings improve our understanding of the pharmacokinetics of nicotine, cotinine, and 3-OH-cotinine across different routes of exposure.

L. acidophilus/L. johnsonii ratio affects slow transit constipation in rats

Slow Transit Constipation (STC) is characterized by impaired colonic motility, but its relationship with gut microbiota remains unclear. This study investigated the correlation between specific gut microbial populations and STC, focusing on the Lactobacillus acidophilus to Lactobacillus johnsonii (A/J) ratio. We used four rat groups: Control (CON), Loperamide-induced STC (LOP), antibiotic-treated (ABX), and antibiotic plus Loperamide (ABX + LOP). Fecal samples were analyzed using 16S rRNA gene sequencing, and serum metabolites were examined through LC–MS. The LOP group showed an increased A/J ratio, while ABX and ABX + LOP groups had decreased ratios. Notably, the ABX + LOP group did not develop STC symptoms. Metabolomic analysis revealed alterations in key metabolites across groups, including changes in levels of guanidinoacetate, glycine, l-glutamine, nicotine, and nicotinate d-ribonucleotide in the LOP group, and variations in l-glutamine, l-phenylalanine, l-tyrosine, histamine, d-ornithine, and lecithin in the ABX and ABX + LOP groups. Our findings suggest a correlation between the A/J ratio and STC development, offering insights into STC pathophysiology and potential microbiome-targeted therapies.

Urine levels of nicotine and its metabolites in young population exposed to second-hand smoke in nightclubs: a pilot study.

The aim of this study was to investigate the extent of second-hand smoke exposure in younger population visiting nightclubs in Croatia by comparing the levels of nicotine and its main metabolites cotinine and trans-3'-hydroxycotinine (3HC) in urine samples taken from 22 participants before and after spending about three hours in a nightclub, stratified by smoking status (smokers and non-smokers). The samples were prepared by liquid-liquid extraction and analysed with gas chromatography-mass spectrometry. The presence of nicotine, cotinine, and 3HC was confirmed in all urine samples. Their median concentrations significantly differed between the two measurements in non-smokers. Our findings show that even a three-hour exposure to second-hand smoke can significantly increase the levels of nicotine and its metabolites in urine, which are indicative of exposure to other, harmful tobacco smoke substances. They also call for raising awareness of the health risks of exposure to second-hand smoke in the general population and among individuals who frequent nightclubs in particular.

Evaluating the Forensic Inferences of Oral Nicotine Ingestion: Autopsy Case Review, Animal Experimentation, and Legal Implications

Nicotine, a highly lipophilic alkaloid derived from Nicotiana tabacum and Nicotiana rustica, can be lethal even in small doses when ingested in concentrated forms like e-cigarette liquids. This study examined a murder case in South Korea where a 52-year-old man was allegedly killed by oral administration of nicotine. Despite the absence of typical signs, such as chemical burns or vomiting, the case posed questions about the lethal concentration of nicotine and the presence of gastrointestinal symptoms in nicotine poisoning. Through literature review, autopsy analysis, and animal experiments, this study evaluated the forensic evidence presented in court. The results indicated that lethal nicotine levels could be lower than established previously, and death could occur without gastrointestinal injury or vomiting. Our findings supported the court's conviction decision, emphasizing the variability of symptoms in nicotine toxicity and the importance of scientific evidence in legal proceedings. The results of this study highlight the role of forensic medicine in clarifying scientific uncertainties in judicial contexts, particularly in cases involving toxic substances.

Variability in addictive and carcinogenic potential of smokeless tobacco products marketed in Mumbai, India: a surveillance study

India has the highest incidence worldwide of smokeless tobacco (SLT)-associated oral cancer, accounting for nearly 70% of all SLT users globally. Nicotine and tobacco-specific N-nitrosamines (TSNA) play critical roles in the addictive and carcinogenic potential, respectively, of SLT products. Our group has previously reported substantial variability in nicotine and TSNA levels across a small SLT product sample in India, calling for systematic surveillance. However, there is no information available on the current levels of these constituents in Indian SLT. We analysed 321 samples representing 57 brands of eight popular types of manufactured SLT products purchased from five local markets in Mumbai, India between August, and September 2019. The sampling locations were Mumbai Central, Kurla, Thane, Vashi, and Airoli. Product pH, moisture content, total and unprotonated (biologically available) nicotine, and TSNA levels were measured at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbai. Total nicotine content ranged from 0.45 to 35.1mg/g across products. The unprotonated nicotine fraction contributed 0.1-100% of the total nicotine content. The carcinogenic TSNA levels ranged 0.06-76 ug/g for N'-nitrosonornicotine (NNN), 0.02-19.2 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 0.01-6.51 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Consistent with our previous study, we observed substantial variations across different brands of the same product type. This is the most extensive and the first within-country study to report brand-specific nicotine and TSNA levels in SLT products marketed in Mumbai, India. Our results show that levels of these constituents remain extremely variable across Indian SLT and are strikingly high in many products. Enhanced public education and continued efforts to reduce SLT use prevalence in India are critical for reducing the global burden of SLT-associated morbidity and mortality. Regulation of nicotine and TSNA levels in SLT products should be considered. This work was supported by the National Institutes of Health (USA) grant R01-TW010651 and, in part, by grants R01-CA180880 and R50-CA211256. The LC-MS/MS analysis was supported in part by XII Plan project funding from the Department of Atomic Energy, Government of India.

From smoke to stroke: quantifying the impact of smoking on stroke prevalence

PurposeThe objective of this study is to assess the impact of smoking on stroke prevalence and to delineate the relationship between smoking-related factors and the risk of stroke, incorporating an analysis of demographic variations influencing this association.MethodsOur analysis encompassed 9,176 participants, evaluating clinical attributes alongside smoking-related characteristics such as duration of cigarette consumption, and levels of nicotine, tar, and carbon monoxide. We employed weighted univariate logistic regression and restricted cubic splines to examine the association between smoking indicators and stroke risk, complemented by subgroup analyses for demographic differentiation.ResultsThe overall prevalence of stroke in our cohort was 3.4%. Statistically significant associations were found between stroke incidence and factors such as age, gender, education, and marital status (p < 0.05). Adjusted logistic regression models showed increased odds ratios (ORs) for stroke with higher nicotine and carbon monoxide levels across progressively adjusted models: Model 1 (unadjusted), Model 2 (adjusted for age, gender), Model 3 (further adjusted for education, marital status, BMI, PIR), and Model 4 (fully adjusted for additional factors including hypertension, hyperlipidemia, diabetes, and drinking). Specifically, ORs for nicotine increased from 2.39 in Model 1 to 2.64 in Model 4; for carbon monoxide, from 1.10 to 1.11 over the same models.​The threshold analysis using restricted cubic splines revealed critical points for stroke risk increase at smoke exposure levels of 410 units, tar 12 mg, nicotine 1.1 mg, and carbon monoxide 12 ppm. Above these thresholds, stroke risk escalates significantly. Additionally, the presence of family smoking history was associated with higher stroke risks compared to those without such history.ConclusionThis study confirms that smoking significantly contributes to increased stroke risk, particularly through exposure to nicotine and carbon monoxide. The findings emphasize the necessity for tailored stroke prevention strategies that specifically address smoking behaviors and consider demographic susceptibilities. Incorporating smoking-related indicators into risk assessment models could enhance the precision of stroke prevention efforts.

Assessing nicotine pharmacokinetics of new generation tobacco products and conventional cigarettes: a systematic review and meta-analysis.

New generation tobacco products (NGPs) hold promises as modified-risk alternatives to conventional cigarettes (CCs), given their comparable characteristics. This study investigated the nicotine pharmacokinetics (PK) of NGPs, encompassing closed pod systems, refillable e-cigarettes (ECs), and heated tobacco products (HTPs), in comparison to CCs through systematic review and meta-analysis. A comprehensive search was conducted on PubMed, Embase, and Web of Science for articles published between January 2013 and July 2023. Maximum nicotine concentration (Cmax), time to the peak concentration (Tmax), and total nicotine exposure (area under the concentration-time curve, AUC) were extracted to evaluate nicotine delivery PK. Random effects meta-analyses were performed to determine pooled standardized mean differences (SMD), facilitating a comparison of PK profiles between NGPs and CCs. Subgroup analyses exploring flavors and nicotine concentrations across NGPs, and CCs were also conducted. The meta-analysis incorporated 30 articles with 2728 participants. Cmax and AUC were significantly lower for NGPs, while Tmax demonstrated statistical similarity compared to CCs. Among three NGPs, Cmax and AUC were lower for closed pod systems and refillable ECs. In HTPs, Cmax was statistically similar while AUC was lower compared to CCs. Tmax was statistically similar in closed pod systems and HTPs compared to that of CCs. No significant difference was observed in the comparisons of PK between each type of NGPs versus CCs. NGPs delivered less nicotine than CCs but reached Cmax over a similar timeframe, indicating that NGPs may serve as modified-risk alternatives with lower nicotine delivery to CCs for craving relief and smoking cessation. This study suggested that NGPs, such as the closed pod systems, the refillable ECs, and the HTPs, delivered either lower or comparable nicotine levels and achieved peak nicotine concentration at a similar rate as CCs. Our findings carry implications that NGPs can serve as modified-risk nicotine alternative to CCs in helping smokers to manage cravings and potentially quit smoking, thereby highlighting their value in the field of tobacco harm reduction.

Nicotine inhalation and metabolism triggers AOX-mediated superoxide generation with oxidative lung injury

With the increasing use of vaping devices that deliver high levels of nicotine (NIC) to the lungs, sporadic lung injury has been observed. Commercial vaping solutions can contain high NIC concentrations of 150 mM or more. With high NIC levels, its metabolic products may induce toxicity. NIC is primarily metabolized to form NIC iminium (NICI) that is further metabolized by aldehyde oxidase (AOX) to cotinine. We determine that NICI in the presence of AOX is a potent trigger of superoxide generation. NICI stimulated superoxide generation from AOX with Km=2.7 μM and Vmax=794 nmol/min/mg measured by cytochrome-c reduction. EPR spin-trapping confirmed that NICI in the presence of AOX is a potent source of superoxide. AOX is expressed in the lungs and chronic e-cigarette exposure in mice greatly increased AOX expression. NICI or NIC stimulated superoxide production in lungs of control mice with even greater increase after chronic e-cigarette exposure. This superoxide production was quenched by AOX inhibition. Furthermore, e-cigarette-mediated NIC delivery triggered oxidative lung damage that was blocked by AOX inhibition. Thus, NIC metabolism triggers AOX-mediated superoxide generation that can cause lung injury. Therefore, high uncontrolled levels of NIC inhalation, as occur with e-cigarette use, can induce oxidative lung damage.

A novel alcohol+nicotine co-use self-administration procedure reveals sex differences and differential alteration of mesocorticolimbic TLR- and cholinergic-related neuroimmune gene expression in rats

Although alcohol and nicotine are two of the most commonly co-used drugs with upwards of 90% of adults with an alcohol use disorder (AUD) in the US also smoking, we don't tend to study alcohol and nicotine use this way. The current studies sought to develop and assess a novel alcohol + nicotine co-access self-administration (SA) model in adult male and female Long-Evans rats. Further, both drugs are implicated in neuroimmune function, albeit in largely opposing ways. Chronic alcohol use increases neuroinflammation via toll-like receptors (TLRs) which in turn increases alcohol intake. By contrast, nicotine produces anti-inflammatory effects, in part, through the monomeric alpha7 receptor (ChRNa7). Following long-term co-access (6 months), rats reliably administered both drugs during daily sessions, however males generally responded for more alcohol and females for nicotine. This was reflected in plasma analysis with translationally relevant intake levels of both alcohol and nicotine, making it invaluable in studying the effects of co-use on behavior and CNS function. Moreover, male rats show sensitivity to alterations in alcohol concentration whereas females show sensitivity to alterations in nicotine concentration. Rats trained on this procedure also developed an anxiogenic phenotype. Finally, we assessed alterations in neuroimmune-related gene expression in the medial prefrontal cortex – prelimbic, (mPFC-PL), nucleus accumbens core (AcbC), and ventral tegmental area (VTA). In the AcbC, where α7 expression was increased and β2 was decreased, markers of pro-inflammatory activity were decreased, despite increases in TLR gene expression suggesting that co-use with nicotine modulates inflammatory state downstream from the receptor level. By contrast, in mPFC-PL where α7 was not increased, both TLRs and downstream proinflammatory markers were increased. Taken together, these findings support that there are brain regional and sex differences with co-use of alcohol + nicotine SA and suggest that targeting nicotinic α7 may represent a novel strategy for treating alcohol + nicotine co-dependence.

E-Cigarette Nicotine Delivery Among Young Adults by Nicotine Form, Concentration, and Flavor

Concerns have been raised about the abuse liability of modern e-cigarettes that use acidic additives to form nicotine salts, making the inhalation of nicotine smoother than freebase nicotine. To examine the effects of nicotine form and concentration and e-liquid flavor on subjective effects ratings, vaping behavior, and nicotine uptake among young adults who use e-cigarettes. In this single-blind, within-participant, crossover randomized clinical trial, a convenience sample of young adults aged 21 to 25 years who currently used e-cigarettes was recruited from December 2021 to August 2023, for in-person research laboratory visits in Columbus, Ohio. Participants completed up to 9 vaping sessions, starting with their usual e-cigarette brand in the first session followed by 1 of 8 laboratory-prepared e-liquids in a randomly assigned order in each subsequent session. Prepared e-liquids varied by nicotine form (salt-based vs freebase), nicotine concentration (5% vs 1% weight per weight), and flavor (menthol vs tobacco). Each session included a 5-minute, 10-puff standardized vaping period followed by 30 minutes of ad libitum vaping. At 4 time points (0, 5, 10, and 35 minutes) during each vaping session, plasma samples were collected for assessing nicotine uptake, and self-reports of urges, craving, and withdrawal were collected via questionnaires. Positive subjective effects were self-reported after 35 minutes of vaping using a visual analog scale; urges and cravings were reported using the Questionnaire of Smoking Urges (QSU). Puff topography data were collected throughout each vaping session. Seventy-two participants (mean [SD] age, 22.4 [1.4] years; 42 [58.3%] female) who sampled at least 1 laboratory-prepared e-liquid composed the analytic sample. Salt-based (vs freebase) nicotine e-liquids increased nicotine intake, with 5% salt-based e-liquids delivering the highest mean plasma levels of nicotine (11.2 ng/mL [95% CI, 9.3-13.2 ng/mL] at 5 minutes; 17.2 ng/mL [95% CI, 14.3-20.1 ng/mL] at 35 minutes) irrespective of flavors. Higher positive subjective effect ratings (eg, for liking) were received by salt-based (42.8; 95% CI, 39.4-46.1) vs freebase (32.0; 95% CI, 28.6-35.3) nicotine, 1% (43.4; 95% CI, 40.2-46.6) vs 5% (31.2; 95% CI, 27.7-34.6) nicotine, and menthol-flavored (43.2; 95% CI, 39.7-46.7) vs tobacco-flavored (31.5; 95% CI, 28.4-34.7) e-liquids. Salt-based and 1% but not menthol-flavored nicotine elicited more intense puffing (eg, 25% [95% CI, 12%-40%] more total puffs for nicotine salts vs freebase). All study e-liquids reduced urges and cravings, with 5% vs 1% nicotine being more effective (mean [SE] QSU-Desire score at 35 minutes, 15.4 [0.5] vs 16.7 [0.5]). In this crossover randomized clinical trial among young adult e-cigarette users, salt-based (vs freebase) nicotine e-liquids increased nicotine intake and yielded more positive subjective effects ratings and intense puffing behaviors, suggesting higher abuse potential. Restricting the level of acidic additives and menthol flavoring may reduce the addictiveness of e-cigarettes. ClinicalTrials.gov Identifier: NCT05458895.

Biosynthesized gold nanoparticles for enhanced determination of nicotine in heated tobacco products

An electrochemical sensor for nicotine determination in heated tobacco products (HTPs) was developed using biosynthesized AuNPs from Ceiba pentandra leaf extract. The biosynthesis process was optimized by investigating the effects of HauCl4 concentration, extract volume, reaction temperature, and time on the formation of gold nanoparticles (AuNPs). The biosynthesized AuNPs were characterized using various techniques, confirming their crystallinity, spherical morphology, and uniform size distribution with an average diameter of 19.8 ± 3.6 nm. The AuNP modified glassy carbon electrode (AuNP/GCE) exhibited enhanced electrochemical performance compared to the bare GCE, facilitating efficient oxidation of nicotine. The AuNP/GCE sensor demonstrated a wide linear range of 0.02–280 µmol L−1 and a low limit of detection of 0.01 µmol L−1 for nicotine determination. The sensor showed excellent selectivity towards nicotine in the presence of common interfering substances, with negligible responses (<5 % change) to uric acid, paracetamol, glucose, melamine, L-cysteine, and dopamine. The AuNP/GCE sensor's applicability was validated by analyzing nicotine levels in real HTP samples, with excellent recovery rates (97.6–102.4 %) and good agreement with the HPLC (R2 = 0.998). The biosynthesized AuNP-based electrochemical sensor offers a rapid, sensitive, eco-friendly, and cost-effective approach for nicotine determination in HTPs, providing a valuable tool for quality control and regulatory purposes.

Modelling the nicotine pharmacokinetic profile for e-cigarettes using real time monitoring of consumers’ physiological measurements and mouth level exposure

Pharmacokinetic (PK) studies can provide essential information on abuse liability of nicotine and tobacco products but are intrusive and must be conducted in a clinical environment. The objective of the study was to explore whether changes in plasma nicotine levels following use of an e-cigarette can be predicted from real time monitoring of physiological parameters and mouth level exposure (MLE) to nicotine before, during, and after e-cigarette vaping, using wearable devices. Such an approach would allow an -effective pre-screening process, reducing the number of clinical studies, reducing the number of products to be tested and the number of blood draws required in a clinical PK study Establishing such a prediction model might facilitate the longitudinal collection of data on product use and nicotine expression among consumers using nicotine products in their normal environments, thereby reducing the need for intrusive clinical studies while generating PK data related to product use in the real world.An exploratory machine learning model was developed to predict changes in plasma nicotine levels following the use of an e-cigarette; from real time monitoring of physiological parameters and MLE to nicotine before, during, and after e-cigarette vaping. This preliminary study identified key parameters, such as heart rate (HR), heart rate variability (HRV), and physiological stress (PS) that may act as predictors for an individual’s plasma nicotine response (PK curve). Relative to baseline measurements (per participant), HR showed a significant increase for nicotine containing e-liquids and was consistent across sessions (intra-participant). Imputing missing values and training the model on all data resulted in 57% improvement from the original’learning’ data and achieved a median validation R2 of 0.70.The study is in its exploratory phase, with limitations including a small and non-diverse sample size and reliance on data from a single e-cigarette product. These findings necessitate further research for validation and to enhance the model's generalisability and applicability in real-world settings. This study serves as a foundational step towards developing non-intrusive PK models for nicotine product use.