Electronic Cigarette Liquids Research Articles

Electronic Cigarette Liquid Constituents Induce Nasal and Tracheal Sensory Irritation in Mice in Regionally Dependent Fashion.

IntroductionElectronic cigarettes (e-cigs) are currently used by millions of adults and adolescents worldwide. Major respiratory symptoms, such as coughing reported by e-cig users, including patients with e-cig, or vaping, product use-associated lung injury (EVALI), indicate e-cig constituent-induced sensory irritation. However, e-cig constituent-induced nociceptive activity in nasal and tracheal respiratory epithelia (RE) and neuronal activation in the trigeminal ganglia and brainstem nuclei, which receive airway chemosensory inputs have not been examined and compared. Comparisons of physiological responses between freebase nicotine and nicotine salts are also missing.Aims and MethodsEvent-related potential (ERP) was recorded electrophysiologically to assess mouse nasal and tracheal RE chemosensory responses to various flavorings, nicotine, including freebase and nicotine salts, e-liquid mixtures, and tussigenic stimuli. Also, mice were subjected to inhalation exposure to aerosol of a vanilla-flavored e-liquid or air (control), and the activated-trigeminal nociceptive neurons and brainstem neurons were examined using immunohistochemistry.ResultsIndividual constituents and mixtures of e-liquids, capsaicin, and citric and acetic acids evoked significantly larger ERP in the nose than in the trachea with the exception of menthol. ERP responses to freebase nicotine were significantly larger than protonated nicotine. Four nicotine salts (benzoate, lactate, levulinate, and salicylate) induced similar responses. Compared with air-exposed mice, e-liquid aerosol-exposed mice showed a significant increase in numbers of activated trigeminal nociceptive neurons and brainstem neurons in the spinal trigeminal nucleus, paratrigeminal nucleus, and nucleus tractus solitarius.ConclusionsE-liquid constituents region-dependently stimulate airway nociceptive chemosensory systems, and freebase nicotine is more potent than protonated nicotine.ImplicationsNeural abnormalities have been implicated in the development of nasal and respiratory illnesses. The higher sensitivity of the nasal nociceptive chemosensory system to nicotine and flavorings may indicate a health risk for e-liquid aerosol-induced upper airway illnesses via neurogenic alteration and warrants further investigation.

Flavor-Toxicant Correlation in E-cigarettes: A Meta-Analysis.

Flavors in electronic cigarette (ECIG) liquids may increase ECIG aerosol toxicity via intact distillation or chemical transformation. For this report, we performed a meta-analysis of the literature to categorize the compounds found in flavored ECIG liquids into a few chemical classes and to predict their possible chemical transformations upon ECIG liquid aerosolization. This analysis allowed us to propose specific correlations between flavoring chemicals and aerosol toxicants. A literature search was conducted in November 2019 using PubMed. Keywords included terms related to ECIGs and flavors. Studies were included if they reported chemical ingredients of flavored liquids and clearly stated the commercial names of these liquids. The obtained data were visualized on a network diagram to show the common chemical compounds identified in flavored ECIG liquids and categorize them into different chemical classes. The systematic literature review included a total of 11 articles. Analysis of the data reported gave a total of 189 flavored liquids and 173 distinct chemical compounds that were categorized into 22 chemical classes according to their functional groups. The subsequent prediction of chemical transformations of these functional groups highlighted the possible correlation of flavor compounds to aerosol toxicants.

E-cigarette Perceptions among HIV-positive Smokers in a Switching Study

Objectives: Cigarette smoking is highly prevalent among persons with HIV (PWH), which is concerning due to their increased risk of developing smoking-related cancers compared to those without HIV. Smoking cessation rates are substantially lower among PWH compared to the general population and less than half report a goal of total abstinence. Given these factors, a switch to electronic cigarettes (ECs), as a form of tobacco harm reduction, may be a viable approach to decreasing tobacco-related morbidity and mortality in PWH. The US Food and Drug Administration has the authority to implement product standards for cigarettes, including ECs and favors. Methods: This qualitative study enrolled 19 HIV-positive smokers into an EC switch study. At Week 12, qualitative interviews were conducted to examine EC perceptions and favor preferences. Results: ECs were viewed as a less harmful, cost-effective method of reducing or eliminating CC smoking, and non-tobacco favors were an essential part of EC appeal and use. Conclusions: Flavored EC liquid seems to enhance the user experience and may influence the user's ability to make a complete switch. Tobacco harm reduction, as a strategy, will only be effective if current evidence guides tobacco regulatory decisions.

Electronic cigarettes — myocardial infarction, hemodynamic compromise during pregnancy, and systolic and diastolic dysfunction: Minireview

The aim of this study was to review the most recent literature on the safety of electronic cigarettes (ECs) in the context of cardiovascular disease and in the context as a tool for smoking cessation and recreational purposes. The format of this review begins with relevant research from the basic sciences and follows through with a pertinent review of clinical trials. Daily use of ECs has implications in myocardial infarction (MI) with an odds ratio of 1.70 compared to healthy, nonsmokers and even worse risk for MI with dual use of combustible cigarettes together with EC with an odds ratio of 4.62. Studies measuring cardiac function with echocardiography reported both systolic and diastolic dysfunction along with reduced ejection fractions. Platelet aggregation, endothelial function, and hemodynamics during pregnancy were all but some of the pernicious cardiovascular implications of EC exposure. Though more studies need to be done on the topic of EC use and cardiovascular disease, the majority of studies considered in this review concluded some level of harm albeit in some instances less than that of traditional combustible cigarettes. ECs are toxic to human beings and their harmful effects cannot be overlooked. There is some favorable evidence of efficacy in smoking cessation though mixed with concern of chronic EC use. It will take decades to collect data for chronic EC use on long term sequelae, such as lung cancer. Though more and more reports of acute lung injury and hospitalizations related to EC use have been reported. Due to undergoing investigations of possible harm and life threatening complications of EC use, we cannot recommend ECs as safer or a more efficacious method of smoking cessation to traditional nicotine replacement therapies. A notable consideration for much of the literature reviewed are that standardization of EC use is difficult as device generation and battery voltage, frequency of use, and contents of EC liquid are just some of the vast complicating factors that limit the ability to effectively compare data.

Effects of electronic cigarette heating coil resistance and liquid nicotine concentration on user nicotine delivery, heart rate, subjective effects, puff topography, and liquid consumption.

Electronic cigarette (ECIG) nicotine delivery and other effects can be influenced by device and/or liquid characteristics and user puffing behavior. One class of ECIGs includes "sub-ohm" devices that incorporate heating coils with resistance less than 1 ohm (Ω), lower than that observed in conventional devices (e.g., ≥1.5 Ω). Relative to conventional ECIGs that operate at ≤10 W, low-resistance coils can be used to increase device power (e.g., 40-300 W). However, little is known about the individual and combined effects of ECIG power, manipulated by coil resistance, and liquid nicotine concentration on ECIG acute effects. Experienced ECIG users (N = 32) completed 4 sessions that differed by ECIG power and coil resistance (40.5 W, 0.5 Ω or 13.5 W, 1.5 Ω) and liquid nicotine concentration (3 or 8 mg/ml). In each session, participants used a 4.5-V Kanger SUBOX ECIG in a 10-puff directed and 60-min ad libitum bout. Nicotine delivery, heart rate, subjective effects, puff topography, and liquid consumption were measured. Nicotine delivery was greatest in the 8mg/ml+0.5Ω condition and lowest in the 3mg/ml+1.5Ω condition. The greatest reduction in abstinence symptoms were observed in the 8mg/ml+0.5Ω condition, although the highest ratings for satisfaction and liking were reported in the 3mg/ml+0.5Ω condition. Use of ECIGs containing 3 mg/ml nicotine liquid resulted in longer and larger puffs and increased puff frequency, though high-power/low-resistance ECIGs resulted in greater consumption of ECIG liquid. ECIG device and liquid characteristics and user puff topography should be considered simultaneously when making regulatory decisions aimed at protecting public health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effect of free-base and protonated nicotine on nicotine yield from electronic cigarettes with varying power and liquid vehicle

Nicotine in electronic cigarette (ECIG) liquids can exist in a free-base or protonated (or “salt”) form. Protonated nicotine is less aversive upon inhalation than free-base nicotine, and many ECIG manufacturers have begun marketing protonated nicotine products, often with high nicotine concentrations. Regulations intended to control ECIG nicotine delivery limit nicotine concentration but do not consider nicotine form. In this study, we systematically examined the effect of nicotine form on nicotine yield for varying powers and liquid vehicles. A Kanger Subox Mini-C tank ECIG (0.5 Ω) was used to generate aerosols at varying powers (5–45 W) from liquid solutions that contained either free-base or protonated nicotine at 15 mg/g concentration, with a liquid vehicle consisting of either propylene glycol (PG) or vegetable glycerin (VG), resulting in four different solutions (free-base/PG, free-base/VG, protonated/PG, and protonated/VG). Nicotine yield was quantified using gas chromatography-mass spectrometry. Nicotine yields were not influenced by nicotine form under any condition investigated. At each power level, PG-based liquids resulted in approximately double the nicotine yield of VG-based liquids. Nicotine concentrations in the aerosols matched those of the parent liquids for both the PG and VG conditions. Increasing power led to greater nicotine yield across all conditions. The amount of nicotine emitted by an ECIG is independent of whether the nicotine is free-base or protonated, however the liquid vehicle has a strong effect on yield. Regulations intended to limit nicotine emissions must consider not only nicotine concentration, but also liquid vehicle and device power.

Impact of Atomizer Age and Flavor on In Vitro Toxicity of Aerosols from a Third-Generation Electronic Cigarette against Human Oral Cells.

Electronic cigarettes (ECs) are categorized into generations which differ in terms of design, aerosol production, and customizability. Current and former smokers prefer third-generation devices that satisfy tobacco cravings more effectively than older generations. Recent studies indicate that EC aerosols from first- and second-generation devices contain reactive carbonyls and free radicals and can cause in vitro cytotoxicity. Third-generation ECs have not been adequately studied. Further, previous studies have focused on cells from the respiratory tract, whereas those of the oral cavity, which is exposed to high levels of EC aerosols, have been understudied. We quantified the production of reactive carbonyls and free radicals by a third-generation EC and investigated the induction of cytotoxicity and oxidative stress in normal and cancerous human oral cell lines using a panel of eight commercial EC liquids. We found that EC aerosols produced using a new atomizer contained formaldehyde, acetaldehyde, and acrolein, but did not contain detectable levels of free radicals. We found that EC aerosols generated from only one of the eight liquids tested using a new atomizer induced cytotoxicity against two human oral cells in vitro. Treatment of oral cells with the cytotoxic EC aerosol caused a concomitant increase in intracellular oxidative stress. As atomizer age increased with repeated use of the same atomizer, carbonyl production, radical emissions, and cytotoxicity increased. Overall, our results suggest that third-generation ECs may cause adverse effects in the oral cavity and normal EC use, which involves repeated use of the same atomizer to generate aerosol, may enhance the potential toxic effects of third-generation ECs.

Investigation on the Antibacterial Activity of Electronic Cigarette Liquids (ECLs): A Proof of Concept Study.

The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. The effect of combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. Higher activity was correlated to the presence of flavors and nicotine. In most cases, the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to the presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

Electronic cigarette explosion/burn and poisoning related emergency department visits, 2018-2019.

Electronic cigarette (ECIG) use has increased dramatically in recent years. Negative ECIG-related acute health effects have included explosion/burn injuries from battery failure and child ingestion/poisoning of liquid nicotine. However, there is an urgent need for continued surveillance of ECIG health effects to determine whether these outcomes change as ECIG devices and liquids rapidly evolve. This study updates national estimates of ECIG-related emergency department (ED) visits and describes the context of these injuries. A keyword search of case narrative text was used to identify ECIG-related ED visits in the National Electronic Injury Surveillance System (NEISS) data. These cross-sectional data are designed to be weighted to provide national estimates of consumer product-related injuries treated in EDs. ECIG-related injuries were described and categorized, and sampling weights applied to model national estimates. From 2015 to 2019 there were an estimated 3369 ED visits from ECIG explosion/burn injuries (95% CI=2020, 4718), and an estimated 676 visits from 2019 alone (95% CI=315, 1036). In 2018-2019, there were an estimated 1550 cases of children <5years old ingesting ECIG liquids (95% CI=778, 2322). Despite a notable shift in the US market towards ECIG devices that use lower electrical power and disposable "pods" (e.g., JUUL), liquid chemical ingestion among young children and ECIG explosion/burn injuries persist. Improved product regulations are urgently needed to prevent negative health effects caused by ECIGs, as well as prevent their ingestion and use by children.

Cell invasion, RAGE expression, and inflammation in oral squamous cell carcinoma (OSCC) cells exposed to e-cigarette flavoring.

ObjectiveElectronic cigarettes have given rise to a new, largely unregulated market within the smoking industry. While generally supposed to be less harmful than traditional tobacco smoke, awareness of the biological effects of electronic cigarette liquid is still scarce. Our objective was to determine the impact of electronic cigarette flavoring and nicotine on gingival squamous cell carcinoma invasion, RAGE expression, and the elaboration of pro‐inflammatory molecules.Methods and MaterialsGingival and tongue squamous cell carcinoma cells were exposed to Red Hot or Green Apple flavored electronic cigarette flavoring with or without nicotine. Immunofluorescence determined RAGE expression. Real‐time cellular invasion was assessed using a RTCA DP instrument. Culture medium was assayed for cytokine secretion.ResultsCompared to controls we observed: increased cell invasion in gingival cells with Red Hot electronic cigarette flavoring and decreased cell invasion with Green Apple; decreased cell invasion in tongue cells treated with Red Hot electronic cigarette flavoring and no differences in invasion with Green Apple; flavor and nicotine dependent increases in RAGE expression; and differential expression of IL‐1α, IL‐8, and MMP‐13.ConclusionWe conclude that electronic cigarette flavoring and nicotine orchestrate differential regulation of oral squamous cell carcinoma (OSCC) cell invasion and inflammatory effects. This study provides an important initial step in dissecting RAGE‐mediated mechanisms of cancerous invasion and molecular avenues employed by OSCC.

In vivo assessment of the toxicity of electronic cigarettes to zebrafish (Danio rerio) embryos, following gestational exposure, in terms of mortality, developmental toxicity, and hair cell damage: Toxicity of E-cigs to zebrafish embryos.

With the ban of conventional cigarettes from public spaces, electronic cigarette (E-cig) liquids have emerged as a nicotine replacement treatment for smoking cessation. However, consumers possess little knowledge of the ingredients and health effects of E-cig liquids following exposure. This study evaluated hair cell damage and developmental toxicities following gestational exposure to E-cig liquids. Zebrafish embryos were exposed to E-cig liquids at different concentrations (0.1%, 0.2%, and 0.4%). Embryonic developmental toxicity and hair cell damage was evaluated at 6 and 7 d, respectively, after fertilization. The average number of hair cells in the anterior lateral line (ALL) and posterior lateral line (PLL) following E-cig exposure was compared to that of the control. Morphological abnormalities and heart rate were evaluated. E-cig liquids significantly damaged the hair cells in the ALL, compared to the control (control; 52.85 ± 5.29 cells, 0.1% E-cig; 49.43 ± 7.70 cells, 0.2% E-cig; 40.68 ± 12.00 cells, 0.4% E-cig; 32.14 ± 20.75%; n = 29-40; p < 0.01). At high concentrations, E-cig liquids significantly damaged the hair cells in the PLL (control; 36.88 ± 5.43 cells, 0.1% E-cig; 33.06 ± 5.21 cells, 0.2% E-cig; 30.95 ± 8.03 cells, 0.4% E-cig; 23.72 ± 15.53%, n = 29-40; p < 0.01). No morphological abnormalities in body shape, somites, notochord, tail, and pectoral fin were observed; however, abnormalities were observed in the dorsal fin and heart rate at high concentrations. Thus, gestational exposure to E-cigs significantly damaged hair cells in a concentration-dependent manner and induced developmental toxicities to the dorsal fin and heart rate at high concentrations.

Electronic cigarette liquid substances propylene glycol and vegetable glycerin induce an inflammatory response in gingival epithelial cells.

Information on the effects of propylene glycol (PG) and vegetable glycerin (VG) and on cytotoxicity and subsequent activation of the biological mediators is limited in periodontal diseases. This study analyzes the effect of unflavored PG/VG alone or in combination with nicotine on gingival epithelial cells. The cells were exposed to different PG/VG (± nicotine) concentrations for 24 h and cytotoxicity was evaluated by calorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromid assay. The expressions of interleukin (IL)-6, IL-8, and matrix metalloproteinases (MMPs)-9 were measured using an enzyme-linked immunosorbent assay and a western blotting. Stimulation with PG/VG mixtures reduced cell viability compared to nonexposed controls (p < 0.05). Adding PG/VG increased the levels of IL-6, IL-8, and MMP-9, and the amount of PG had more biological impact compared to the VG amount. The nicotine augmented this effect compared to its nicotine-free counterparts. In western blotting result, MMP-9 was clearly activated in almost all samples. These findings suggest that the main constituents PG/VG are cytotoxic and able to induce biological response in gingival cells in vitro. Despite being advertised as less harmful than conventional cigarettes, electronic cigarette liquid pose certain risks on periodontal cells. Awareness about the effects of electronic cigarettes on periodontal diseases must be increased.

Vaped Humectants in E-Cigarettes Are a Source of Phenols

Electronic cigarettes (ECIGs) have always been promoted as safer alternatives to combustible cigarettes. However, a growing amount of literature shows that while ECIGs do not involve combustion-derived toxicants, thermal degradation of the main constituents of ECIG liquid produces toxicants such as carbonyls. In this study, we report the detection of phenolic compounds in ECIG aerosols using a novel analytical method. The introduced method relies on liquid-liquid extraction to separate phenols from the major constituents of ECIG aerosol: propylene glycol (PG) and vegetable glycerol (VG). Phenol emissions from ECIGs were tested at different powers, puff durations, PG/VG ratios, nicotine benzoate concentrations, and flow rates to assess the influence of these operating parameters on phenol formation. The performance metrics showed that the analytical method has high specificity and reliability to separate and quantify phenolic compounds in ECIG aerosols. Increasing power and puff duration significantly increased all phenol emissions, while flow rate had no significant effects. The phenol profile in the ECIG aerosol was dominated by the unsubstituted phenol that reached comparable levels to those of IQOS, combustible cigarettes, and waterpipe. In contrast, low levels of the more toxic phenolic compounds, like catechol and hydroxyquinone, were quantified in ECIG aerosols. Emission of toxicants is presented, for the first time in this study, as the yield per unit of time, or flux (μg/s), which is more suitable for interstudy and interproduct comparison. This work demonstrates a robust analytical method for isolating and quantifying phenol emissions in ECIG aerosols. Using this method, the study shows that phenols, which are not present in the simple solution of nicotine benzoate dissolved in mixtures of PG/VG, are formed upon vaping. Phenol emissions are independent of the nicotine benzoate concentration but significantly correlated with the PG/VG ratio. Emissions increased with power and puff duration, consistent with conditions that lead to a higher temperature and greater thermal degradation.

User Perceptions of Different Electronic Cigarette Flavors on Social Media: Observational Study.

BackgroundThe number of electronic cigarette (e-cigarette) users has been increasing rapidly in recent years, especially among youth and young adults. More e-cigarette products have become available, including e-liquids with various brands and flavors. Various e-liquid flavors have been frequently discussed by e-cigarette users on social media.ObjectiveThis study aimed to examine the longitudinal prevalence of mentions of electronic cigarette liquid (e-liquid) flavors and user perceptions on social media.MethodsWe applied a data-driven approach to analyze the trends and macro-level user sentiments of different e-cigarette flavors on social media. With data collected from web-based stores, e-liquid flavors were classified into categories in a flavor hierarchy based on their ingredients. The e-cigarette–related posts were collected from social media platforms, including Reddit and Twitter, using e-cigarette–related keywords. The temporal trend of mentions of e-liquid flavor categories was compiled using Reddit data from January 2013 to April 2019. Twitter data were analyzed using a sentiment analysis from May to August 2019 to explore the opinions of e-cigarette users toward each flavor category.ResultsMore than 1000 e-liquid flavors were classified into 7 major flavor categories. The fruit and sweets categories were the 2 most frequently discussed e-liquid flavors on Reddit, contributing to approximately 58% and 15%, respectively, of all flavor-related posts. We showed that mentions of the fruit flavor category had a steady overall upward trend compared with other flavor categories that did not show much change over time. Results from the sentiment analysis demonstrated that most e-liquid flavor categories had significant positive sentiments, except for the beverage and tobacco categories.ConclusionsThe most updated information about the popular e-liquid flavors mentioned on social media was investigated, which showed that the prevalence of mentions of e-liquid flavors and user perceptions on social media were different. Fruit was the most frequently discussed flavor category on social media. Our study provides valuable information for future regulation of flavored e-cigarettes.

A Social Media Study on the Associations of Flavored Electronic Cigarettes With Health Symptoms: Observational Study.

BackgroundIn recent years, flavored electronic cigarettes (e-cigarettes) have become popular among teenagers and young adults. Discussions about e-cigarettes and e-cigarette use (vaping) experiences are prevalent online, making social media an ideal resource for understanding the health risks associated with e-cigarette flavors from the users’ perspective.ObjectiveThis study aimed to investigate the potential associations between electronic cigarette liquid (e-liquid) flavors and the reporting of health symptoms using social media data.MethodsA dataset consisting of 2.8 million e-cigarette–related posts was collected using keyword filtering from Reddit, a social media platform, from January 2013 to April 2019. Temporal analysis for nine major health symptom categories was used to understand the trend of public concerns related to e-cigarettes. Sentiment analysis was conducted to obtain the proportions of positive and negative sentiment scores for all reported health symptom categories. Topic modeling was applied to reveal the topics related to e-cigarettes and health symptoms. Furthermore, generalized estimating equation (GEE) models were used to quantitatively measure potential associations between e-liquid flavors and the reporting of health symptoms.ResultsTemporal analysis showed that the Respiratory category was consistently the most discussed health symptom category among all categories related to e-cigarettes on Reddit, followed by the Throat category. Sentiment analysis showed higher proportions of positive sentiment scores for all reported health symptom categories, except for the Cancer category. Topic modeling conducted on all health-related posts showed that 17 of the top 100 topics were flavor related. GEE models showed different associations between the reporting of health symptoms and e-liquid flavor categories, for example, lower association of the Beverage flavors with Respiratory compared with other flavors and higher association of the Fruit flavors with Cardiovascular than other flavors.ConclusionsThis study identified different potential associations between e-liquid flavors and the reporting of health symptoms using social media data. The results of this study provide valuable information for further investigation of the health effects associated with different e-liquid flavors.

Rapid identification of nicotine in electronic cigarette liquids based on surface-enhanced Raman scattering.

Nicotine-containing electronic cigarette liquid (e-liquid) is prohibited in many countries, creating requirements for rapid detection approaches for on-site inspection or screening for large amounts of samples. Here, we demonstrate a simple way to identify nicotine using surface-enhanced Raman scattering (SERS) with substrates made of silver nanoparticle arrays imbedded in anodic aluminum oxide nanochannels (Ag/AAO). Compared with the reported colloidal nanoparticle-based SERS, that required serial dilutions to enable colloid aggregation in the viscous e-liquid, a small amount of undiluted e-liquid sample can be directly added onto our solid-phase Ag/AAO substrate without any pre-treatment. The sensitivity of our SERS measurements is 2–3 orders of magnitude higher than that required for identification of nicotine in e-liquid, which is typically around 1000–18,000 ppm. Using such nanoparticle array-based SERS, we have tested 22 commercially available e-liquid products, using the corresponding gas chromatography-mass spectrometry (GC–MS) reports as the reference. The SERS measurements were done within one hour and successfully identified 20 samples. Only 2 samples showed SERS interference from ingredients that were not suitable for SERS analysis.

Conversion of Cannabidiol (CBD) into Psychotropic Cannabinoids Including Tetrahydrocannabinol (THC): A Controversy in the Scientific Literature.

Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient. Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse. While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.

Electronic cigarette use among Italian smokers: patterns, settings, and adverse events.

Information is scanty on the patterns and settings of electronic cigarette use and on its possible adverse events. To fill the knowledge gap on these issues, we conducted a survey among ever-smokers attending smoking cessation services (SCS) in Italy. In 2016-2018, we enrolled 395 ever-smokers aged ⩾18 years who were current or former electronic cigarette users in 12 SCS from northern, central, and southern Italy. In all, 12.4% of ever smokers were regular, 9.4% occasional, and 78.2% past users of electronic cigarettes. Of all users, 93.8% consumed electronic cigarettes with nicotine, 95.9% used refillable devices, and 76.6% purchased electronic cigarette devices or liquids in vape shops. The mean duration of use was 3.7 months and the mean number of puffs per day was 86. Among users, 71.5% used electronic cigarettes in at least 1 smoke-free indoor environment, 53.7% in workplaces, 49.5% in restaurants and bars, 33.5% in train/metro stations or airports, and 18.4% in public transports. The use of electronic cigarettes in smoke-free environments significantly decreased with age and increased with duration of use and nicotine dependence. In our sample, 47.1% reported at least 1 adverse event attributable to electronic cigarette use: 19.5% dry cough, 12.0% dry mouth, 7.6% throat or mouth irritation, and 6.8% sore throat. In Italy, most conventional cigarette smokers use electronic cigarettes where smoking conventional cigarettes is prohibited. About half of users reported 1 or more symptoms attributable to electronic cigarettes, despite the relatively short duration of use.

Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice

BackgroundThe use of electronic cigarettes has increased over the past decade. To determine how the abuse liability of electronic cigarette liquids (e-liquids) differs from nicotine alone, and to determine the impact of flavor, we compared nicotine-containing fruit- and tobacco-flavored e-liquids, and their nicotine-free versions, to nicotine alone in mouse models of oral consumption, reward and aversion. MethodsAdult male C57BL/6 J mice voluntarily consumed oral nicotine, equivalent nicotine concentrations of fruit- and tobacco-flavored e-liquid, and equivalent dilutions of the nicotine-free versions in 2-bottle choice tests. Conditioned place preference and place aversion were assessed with peripherally administered e-liquids or nicotine. Serum nicotine and cotinine levels were measured after subcutaneous injections of e-liquid or nicotine. ResultsMice showed higher consumption and preference for the fruit-flavored e-liquid compared with nicotine alone. This increase was not due to the flavor itself as consumption of the nicotine-free fruit-flavored e-liquid was not elevated until the highest concentration tested. The increased consumption and preference were not observed with the tobacco-flavored e-liquid. The conditioned place preference, place aversion and nicotine pharmacokinetics of the fruit-flavored e-liquid were not significantly different from nicotine alone. ConclusionsOur data suggest that fruit, but not tobacco flavor, increased the oral consumption of e-liquid compared with nicotine alone. Moreover, this enhancement was not due to increased consumption of the flavor itself, altered rewarding or aversive properties after peripheral administration, or altered pharmacokinetics. This flavor-specific enhancement suggests that some flavors may lead to higher nicotine intake and increased use of e-liquids compared with nicotine alone.

E-Cigarette Quality Control: Impurity and Nicotine Level Analysis in Electronic Cigarette Refill Liquids.

This work targets mainly the quality control of electronic cigarette liquids. It relies on an analytical control of a “32-product” sample made of several types of e-cigarette liquids taken from various supermarkets and tobacconist's offices in Morocco. All along this study, we made sure to check both the conformity of the nicotine level indicated in the packaging of each product and the existence of any other components inside the product, especially toxic or unknown impurities. The method used for this study is known under the name of high-performance liquid chromatography. For statistical analysis, we used Student's t-test for a single sample in order to analyze the relative differences between nicotine quantity reported in the product and the one measured during our experiment. Finally, we used linear regression test to determine the relationship between the nicotine level accuracy on the packaging and the level of toxic impurities in the products. The differences between the nicotine concentrations reported in the packages and the measured ones varied from −100% to +3.3%. The study showed that 31% of analyzed products have an accurate indication of the level of nicotine on the packaging. However, 47% of the studied products showed more than 20% difference between measure and packaging indication. In all analyzed samples, the level of impurities altered from 0 to 32.6%. Furthermore, the level of the nicotine breakdown products did not exceed 2% of the nicotine content in pretty much all of the samples. The actual nicotine content of electronic cigarette refill liquids is not always as precise as what is stated on the packaging; in addition to the level of impurities detected in several brands and that exceeds the European Pharmacopoeia standards, some may even present a risk of causing toxicological damage.