Nicotine E-liquid Research Articles

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.

Determination of Nicotine Protonation State in E-Liquids by Low-Resolution Benchtop NMR Spectroscopy.

Over several years, e-liquids with "nicotine salts" have gained considerable popularity. These e-liquids have a low pH, at which nicotine occurs mostly in its monoprotonated form. Manufacturers usually accomplish this by the addition of an organic acid, such as levulinic acid, benzoic acid, or lactic acid. Nicotine in its protonated form can be more easily inhaled, enhancing the addictiveness and attractiveness of products. Several techniques have been described for measuring the protonation state of nicotine in e-liquids. However, nuclear magnetic resonance (NMR) spectroscopy is particularly suited for this purpose because it can be performed on unaltered e-liquids. In this article, we demonstrate the suitability of a benchtop NMR (60 MHz) instrument for determining the protonation state of nicotine in e-liquids. The method is subsequently applied to measure the protonation state of 33 commercially available e-liquids and to investigate whether the vaping process alters the protonation state of nicotine. For this purpose, the protonation state in the condensed aerosol obtained by automated vaping of different e-liquids was compared with that of the original e-liquids. Two distinct populations were observed in the protonation state of nicotine in commercial e-liquids: free-base (fraction of free-base nicotine αfb > 0.80) and protonated (αfb < 0.40). For 30 e-liquids out of 33, the information on the packaging regarding the presence of nicotine salt was in agreement with the observed protonation state. Three e-liquids contained nicotine salt, even though this was not stated on the packaging. Measuring the protonation state of nicotine before and after (machine) vaping revealed that the protonation state of e-liquids is not affected by vaping. In conclusion, it is possible to determine the nicotine protonation state with the described method. Two clusters can be distinguished in the protonation state of commercial e-liquids, and the protonation state of nicotine remains unchanged after vaping.

Nicotine strength of e-liquids used by adult vapers in Great Britain: A population survey 2016 to 2024.

In March 2024, the UK government announced plans to introduce a Vaping Products Duty that will tax e-liquids based on their nicotine strength. This study examined trends in the nicotine strength of e-liquids used by adult vapers and differences in those currently used across relevant subgroups. Nationally-representative, cross-sectional household survey, July 2016 to January 2024. Great Britain. 7981 adult vapers. Participants were asked whether the e-cigarette they mainly use contains nicotine (yes/no) and the e-liquid strength (no nicotine, >0-≤ 6, 7-11, 12-19 or ≥20 mg/ml). We also collected information on the main device type used (disposable/refillable/pod), age, gender, occupational social grade, history of ≥1 mental health conditions, smoking status and (among past-year smokers) level of cigarette addiction. The proportion of vapers in England using high-strength (≥20 mg/ml) e-liquids increased from an average of 3.8% (95% confidence interval [CI] = 2.9-5.0) up to June 2021 to 32.5% (CI = 27.9-37.4) in January 2024 (the vast majority of whom [93.3% in January 2024] reported using exactly 20 mg/ml; the legal limit). This rise was most pronounced among those using disposable e-cigarettes, those aged 18-24 years and all smoking statuses (including never smokers) except long-term (≥1y) ex-smokers. Of those surveyed in 2022-2024 in Great Britain, overall, 89.5% (CI = 88.1-90.8) said they usually used e-cigarettes containing nicotine, 8.7% (CI = 7.5-10.0) used nicotine-free e-cigarettes, and 1.8% (CI = 1.2-2.4) were unsure. The proportion using ≥20 mg/ml was higher among those mainly using disposable (47.9%) compared with pod (16.3%) or refillable (11.5%) devices; never smokers (36.0%), current smokers (28.8%) or recent (<1y) ex-smokers (27.4%), compared with long-term ex-smokers (13.9%); and younger (16-24y; 44.2%) compared with older (≥25y; range 9.4-25.1%) age groups. There were no notable differences across other subgroups of interest. Use of high-strength nicotine e-liquids in England appears to have increased sharply in recent years. Most adult vapers in Great Britain appear to use e-cigarettes that contain nicotine but different subgroups use different strengths: nicotine strengths tend to be higher among those who mainly use disposable devices and those aged 16-24y, and lower among long-term ex-smokers.

Modification of Electronic Nicotine Delivery Systems Among Adolescents and Young Adults.

We assessed awareness and perceptions of, information sources about, and engagement in modifying electronic nicotine delivery systems (ENDS) among adolescents and young adults (AYAs). AYAs (N = 1018) endorsing past-month ENDS use completed a survey on awareness and use of the following modifications: (1) refilling rechargeable cartridges/pods or (2) disposable pods, (3) rewicking or (4) recharging disposable pods, (5) modifying nicotine e-liquids (eg, changing propylene glycol/vegetable glycerin, nicotine), (6) combining nicotine and cannabis for simultaneous vaping, and (7) putting cannabis in ENDS designed for nicotine vaping. Logistic regression assessed how sources of information (eg, friends, social media, nonsocial media Web sites, vape shops) about and perceptions of ENDS modifications associated with ENDS modifications. Refilling (69.0% heard, 40.1% tried) and recharging the battery (66.4% heard, 35.8% tried) of disposable pods were most common. Friends (64.4%) and social media (46.7%) were the most common sources of information. Notable significant associations between information sources and modifications were: 1. nonsocial media Web sites and vape shops with rewicking and recharging disposable devices and modifying nicotine e-liquid; 2. nonsocial media Web sites with refilling rechargeable cartridges/pods and disposable pods; and 3. social media with recharging disposable devices and mixing nicotine and cannabis liquids. Perceptions of reduced harm and "coolness" were associated with various modifications. AYAs are aware of and modify ENDS for purposes unintended by manufacturers. ENDS policies should consider unintended ENDS use to safeguard public health. Prevention efforts should communicate about the potential harms of ENDS modifications.

Quantification of Free Radicals from Vaping Electronic Cigarettes Containing Nicotine Salt Solutions with Different Organic Acid Types and Concentrations.

Electronic (e-) cigarette formulations containing nicotine salts from a range of organic acid conjugates and pH values have dominated the commercial market. The acids in the nicotine salt formulations may alter the redox environment in e-cigarettes, impacting free radical formation in e-cigarette aerosol. Here, the generation of aerosol mass and free radicals from a fourth-generation e-cigarette device was evaluated at 2 wt % nicotine salts (pH 7, 30:70 mixture propylene glycol to vegetable glycerin) across eight organic acids used in e-liquids: benzoic acid (BA), salicylic acid (SLA), lactic acid (LA), levulinic acid (LVA), succinic acid (SA), malic acid (MA), tartaric acid (TA), and citric acid (CA). Furthermore, 2 wt % BA nicotine salts were studied at the following nicotine to acid ratios: 1:2 (pH 4), 1:1 (pH 7), and 2:1 (pH 8), in comparison with freebase nicotine (pH 10). Radical yields were quantified by spin-trapping and electron paramagnetic resonance (EPR) spectroscopy. The EPR spectra of free radicals in the nicotine salt aerosol matched those generated from the Fenton reaction, which are primarily hydroxyl (OH) radicals and other reactive oxygen species (ROS). Although the aerosol mass formation was not significantly different for most of the tested nicotine salts and acid concentrations, notable ROS yields were observed only from BA, CA, and TA under the study conditions. The e-liquids with SLA, LA, LVA, SA, and MA produced less ROS than the 2 wt % freebase nicotine e-liquid, suggesting that organic acids may play dual roles in the production and scavenging of ROS. For BA nicotine salts, it was found that the ROS yield increased with a higher acid concentration (or a lower nicotine to acid ratio). The observation that BA nicotine salts produce the highest ROS yield in aerosol generated from a fourth-generation vape device, which increases with acid concentration, has important implications for ROS-mediated health outcomes that may be relevant to consumers, manufacturers, and regulatory agencies.

Stimulus mediation, specificity and impact of menthol in rats trained to discriminate puffs of nicotine e-cigarette aerosol from nicotine-free aerosol.

It is unclear if e-cigarettes have reduced abuse liability relative to traditional cigarettes, especially when considering advanced devices which deliver nicotine more efficiently. Translatable and predictive animal models are needed to addresses this question. Our goal was to explore the subjective stimulus effects of e-cigarettes by training rats to discriminate puffs of nicotine aerosol from vehicle aerosol using an aerosol delivery system designed to model e-cigarette use patterns in humans. Rats were trained to discriminate between ten, 10s puffs of aerosol generated from 3mg/ml nicotine e-liquid and nicotine-free e-liquid using a food-reinforced operant procedure. Following acquisition, tests were conducted to determine the specificity of the nicotine aerosol stimulus as well as the impact to the stimulus effects of nicotine resulting from the addition of menthol to e-liquid. Rats learned the nicotine aerosol puff vs vehicle puff discrimination in a mean of 25 training sessions. Injected nicotine fully substituted for the stimulus effects of nicotine aerosol. The stimulus effects of nicotine aerosol were blocked by the nicotinic receptor antagonist mecamylamine. The nicotinic receptor partial agonist, varenicline as well as the stimulant d-amphetamine substituted more robustly for nicotine aerosol puffs than did the NMDA antagonist, ketamine. Menthol enhanced the stimulus effects of nicotine aerosol without altering nicotine blood plasma levels. Nicotine aerosol puffs can function as a training stimulus in rats. The stimulus effects were CNS-mediated and receptor specific. Menthol appears to enhance the stimulus effects of nicotine aerosol through a pharmacodynamic rather than pharmacokinetic mechanism.

Chromatography and Spectroscopy Methods for the Analysis of Nicotine and Other Chemical Ingredients in E-Liquid Formulation: A Review

Spectroscopy and chromatography methods have become the most preferred techniques for detecting ingredients in e-liquid analysis. Both methods are widely used for separating and quantifying volatile compounds in a sample, providing individual chemical information in complex mixtures. This paper aims to review the detection and quantification of nicotine and other chemical ingredients in e-liquid used in e-cigarettes. E-cigarettes use the evaporation-condensation principle of aerosolization to produce an inhaled vapor containing nicotine, excipients, and flavoring agents. This review covers sample preparation, identification, and quantification of nicotine and other ingredients using chromatography and spectroscopy analysis. The spectroscopy methods are useful for quickly identifying and quantifying volatile compounds, including propylene glycol (PG), vegetable glycol (VG), and nicotine, while spectroscopic methods, particularly the Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) method, have lower analytical performance compared to chromatography methods in detecting nicotine and other chemical ingredients. Based on the review, chromatographic methods are the primary option for analyzing nicotine in all e-liquid samples, offering a better alternative for a future study with the presence of multiple detectors.

Electronic Nicotine Delivery Systems and E-Liquid Modifications to Vape Cannabis Depicted in Online Videos

Electronic nicotine delivery systems (ENDS) were created to vape nicotine e-liquids; however, social media demonstrates increased ENDS modifications to vape cannabis. Analysis of social media content helps with understanding ENDS modifications for cannabis use, overlapping markets for ENDS and cannabis, and the need for additional regulation. To analyze online videos for use, modification, and marketing of ENDS to vape cannabis. In this qualitative study, 10 searches were performed on YouTube on July 14, 2022, using different combinations of relevant search terms to identify videos depicting modifications to ENDS and e-liquids to vape cannabis. The first 40 videos from each search (400 videos total, 152 without duplicates) were extracted, of which 59 included depiction or discussion of cannabis vaping content. Content analysis of videos included iterative development of codes, consensus building across team members, and reliability checks. Metadata (ie, video length, number of likes, comments, and views) were extracted for included videos. Coding was performed for uploader type, modifications to ENDS and e-liquids, devices used, cannabis products vaped, age restriction, purchasing links, health claims, and discussion of warning messages and cannabis regulations. Of the 59 videos analyzed, 34 (58%) included tetrahydrocannabinol; 33 (56%), cannabidiol; and 8 (14%), both. A total of 21 videos (36%) were age-restricted, while 25 (42%) included purchasing links for cannabis products, 20 (34%) for ENDS, and 7 (12%) for nicotine e-liquids. Twenty-six videos (44%) made claims about health benefits of vaping cannabis. Forty-one videos (69%) demonstrated vaping manufacturer-made cannabis products (eg, cannabis concentrates) with no modifications needed. Eighteen videos (31%) depicted modifications to e-liquids or ENDS for cannabis use. The most frequent modification was mixing e-liquids with cannabis products to be compatible with ENDS. The most frequently reported reason for modifications was to vape cannabis in public by using the same devices used for nicotine. This qualitative study of online videos found high frequencies of statements about health benefits from vaping cannabis, frequent purchasing links, and inadequate age restrictions. Exposure to such content on social media platforms may increase risk of cannabis vaping among youth. Use of the same devices for multiple substances may also enable dual use and complicate the US Food and Drug Administration's regulation of ENDS.

Assessing the impact of protonating acid combinations in e-cigarette liquids: a randomised, crossover study on nicotine pharmacokinetics

The addition of protonating acids to e-cigarette liquid formulations (e-liquids) enhances nicotine bioavailability in e-cigarette use. However, little is known about the impact of different combinations of protonating acid on nicotine pharmacokinetics. The objectives of this study were to compare pharmacokinetics of nicotine absorption following use of a closed-system e-cigarette, containing e-liquids with two different nicotine levels and with different ratios of three common protonating acids—lactic, benzoic and levulinic. In a randomised, controlled, crossover study, nicotine pharmacokinetics and product liking were assessed for prototype e-liquids used in a Vuse e-cigarette containing either 3.5% or 5% nicotine and varying ratios of lactic, benzoic and/or levulinic acid. During an 8-day confinement period, 32 healthy adult current cigarette smokers/e-cigarette dual users used a single study e-liquid each day during 10-min fixed and ad libitum use periods after overnight nicotine abstinence. For most comparisons, Cmax and AUC0–60 following both fixed and ad libitum puffing were significantly higher for e-liquids containing 5% nicotine compared with 3.5% nicotine. However, Cmax and AUC0–60 were not statistically different for 5% nicotine e-liquids containing varying ratios of lactic, levulinic and benzoic acid when compared to an e-liquid containing lactic acid only. Mean scores for product liking were similar for all e-liquid formulations assessed, regardless of nicotine concentration, acid content, and whether the product was used in a fixed or ad libitum puffing regimen. While e-liquid nicotine concentration significantly affected users’ nicotine uptake, the different combinations of benzoic, levulinic and lactic acid in the e-liquids assessed had limited impact on nicotine pharmacokinetics and product liking scores.

Exploring Differences in Daily Vaping of Nicotine and Cannabis among People Who Use Drugs in New Zealand

Background: Little is known about daily vaping of different substances, particularly cannabis. Aim: To explore daily vaping of cannabis and nicotine products in a sample of people who use drugs in New Zealand. Method: The online New Zealand Drug Trends convenience survey (N = 23,500) was promoted to those aged 16+ via a targeted Facebook™ campaign, with 9,042 reporting vaping in the past six months. Multivariate logistic regression models were fitted to identify predictors of daily vaping of: (i) nicotine e-liquids, (ii) no-nicotine e-liquids, (iii) cannabis e-liquids/oils, (iv)cannabis herb. Results: Forty-two percent of past 6-month vapers used a vaporizing device “daily or near daily” (n = 3,508). Nicotine was most common substance used by daily vapers (96%), followed by dry herb cannabis (12%), no-nicotine e-liquids (10%) and cannabis e-liquid (6%). Daily vaping of no-nicotine e-liquids was associated with abstinence from tobacco use. Frequency of cannabis use was negatively correlated with daily vaping of nicotine liquids and positively correlated with daily vaping of no-nicotine and herbal cannabis. Younger age strongly predicted daily vaping of nicotine and no-nicotine liquids, but the reverse association was observed for daily vaping of herbal cannabis. Māori were less likely to daily vape cannabis herb than NZ Europeans. Daily vaping of both cannabis e-liquid and cannabis herb was associated with medicinal cannabis use. Conclusion: Daily vapers of nicotine and cannabis differed by several characteristics. Younger age group is at risk of daily vaping nicotine and non-nicotine, while herbal cannabis vaping is associated with older and medicinal use, suggesting a need for a nuanced vape policy response.

Strawberry Additive Increases Nicotine Vapor Sampling and Systemic Exposure But Does Not Enhance Pavlovian-Based Nicotine Reward in Mice.

Nicotine is an addictive drug whose popularity has recently increased, particularly among adolescents, because of the availability of electronic nicotine devices (i.e., "vaping") and nicotine e-liquids containing additives with rich chemosensory properties. Some efforts to understand the role of these additives in nicotine reward suggest that they increase nicotine reward and reinforcement, but the sensory contributions of additives, especially in their vapor forms, are largely untested. Here, to better understand how a fruit-flavored (i.e., strawberry) additive influences nicotine reward and aversion, we used a conditioned place preference (CPP) procedure in which nicotine and a strawberry additive were delivered as a vapor to male and female adolescent mice. We found that nicotine vapor alone can lead to a dose-dependent CPP when using a biased design. The strawberry additive did not produce CPP on its own, and we did not observe an effect of the strawberry additive on nicotine vapor-induced reward. Nevertheless, mice exposed to nicotine plus strawberry additive vapor had higher plasma cotinine concentrations, which did not appear to reflect altered nicotine metabolism. Instead, by directly measuring vapor sampling through respiration monitoring, we uncovered an increase in the amount of sniffing toward strawberry-containing nicotine vapor compared with nicotine vapor alone. Together these data indicate that chemosensory-rich e-liquid additives may enhance the perceived sensory profile of nicotine vapors rather than the reward value per se, which leads to overall increased nicotine exposure.

Sensory appeal and puffing intensity of e-cigarette use: Influence of nicotine salts versus free-base nicotine in e-liquids

BackgroundIn the US, nicotine salts (with protonated nicotine instead of free-based nicotine) have been reported to lower the harshness and bitterness of e-cigarette aerosols, making it easier to inhale high levels of nicotine. This study aimed to determine whether nicotine salts also increase sensory appeal at lower concentrations (< 20mg/mL). Moreover, and novel, inhalation intensity of both types of e-liquids was compared. MethodsIn a randomized, double-blinded, within-participants design, healthy adults who use e-cigarettes (n=68) vaped tobacco-flavored e-liquids containing 12mg/mL of free-based nicotine or nicotine salt ad libitum, using their own device, during two online sessions (June-July 2021, Utrecht, The Netherlands). The sensory parameters perceived liking, nicotine intensity, harshness, and pleasantness were rated on a 100-unit visual analog scale. The intensity of use was determined by the recorded puff number, duration and interval. ResultsTest scores on appeal, harshness and puffing behavior parameters showed no significant differences between the nicotine salt and the free-base condition. The average inhalation time was 2.5seconds. Additional analyses found no significant effect of liquid order, age, gender, smoking status, vaping frequency and familiarity with nicotine salts. Significant positive correlations were found between the sensory parameters except for harshness. ConclusionsContrary to a previous study that used higher nicotine concentrations and standardized puffing conditions in a laboratory setting, we did not observe the effects of nicotine salts on sensory appeal in our real-life study paradigm. Moreover, we did not see effects on study parameters related to puffing intensity.

E-cigarette product preferences of Australian adolescent and adult users: a 2022 study

BackgroundResearch that comprehensively documents preferences for different types of novel nicotine products in Australia is lacking, making it difficult for policymakers to determine where public health efforts should be focused. This study thus sought to explore Australian adolescent and adult e-cigarette users’ preferences for different types of e-cigarettes and e-liquids. Purchasing behaviours and sources of e-liquid were also examined.MethodsAn online survey was administered to 4,617 Australians aged 12 + years, 636 of whom had used an e-cigarette in the last 30 days and were the focus of this study. Among users, 45% also smoked tobacco cigarettes, 41% were non-smokers, and 14% had never smoked.ResultsThe majority (82%) of e-cigarette users surveyed reported using nicotine-containing e-liquid in their devices. Fewer (60%) reported using non-nicotine e-liquid. The preference for nicotine over non-nicotine e-liquid was observed among all age and smoking groups. Most users (89%) reported using flavoured e-liquids, with adolescents (96%) significantly more likely than young adults (90%) and adults aged 25 + years (85%) to report using such e-liquids. Fruit flavours were the most popular among all subgroups. In terms of device type, disposable e-cigarettes were the most common product used among almost all groups; the exception being adults aged 25 + years who preferred systems with refillable tanks. Friends and tobacco retailers were the most frequently nominated sources of nicotine e-liquid among adolescents and young adults. Among adults aged 25 + years, tobacco retailers and the Internet were the most frequently nominated sources of these products.ConclusionDisposable e-cigarettes with flavoured, nicotine-containing e-liquid are popular among users of the devices, including adolescents. Measures that restrict the accessibility and availability of flavoured e-liquids and disposable e-cigarettes, and greater enforcement of laws regarding the sale and importation of nicotine e-liquids, are urgently needed to protect youth and never smokers from these products.

Market survey of disposable e-cigarette nicotine content and e-liquid volume

Inaccurate labels on some e-cigarette products have prompted calls for routine testing to monitor product label integrity. The objective of this study was to compare label statements of commercial disposable/non-chargeable e-cigarette products for nicotine concentration and e-liquid volume with analytically verified levels. Commercial e-cigarette samples were analyzed for nicotine concentration (N = 51), e-liquid volume and total nicotine content (N = 39). Twenty-three of the 51 samples analyzed for nicotine deviated from their label statements by more than ± 10%. Deviations ranged from -50.1% to + 13.9%. Thirty of the 39 samples analyzed for e-liquid volume deviated from their label statements by more than ± 10%. Deviations ranged from -62.1% to + 13.3%. Only one brand listed total nicotine on the label. In thirty-one of the 39 samples, calculated total nicotine amount in e-liquid deviated from the amounts calculated from the label metrics by more than ± 10%. Deviations ranged from -66.8% to -1.43%. These findings underscore the need for regulatory enforcement of manufacturing quality control and product labeling practices to optimize the harm reduction potential and consumer experience associated with the use of e-cigarette products.

School-based preventive interventions targeting e-cigarette use among adolescents: a systematic review protocol

IntroductionElectronic cigarette (e-cigarette) use has drastically increased in recent years, particularly among adolescents. This poses several acute and chronic harms to young people, including poisonings, burns, serious lung injury and—where...

Preliminary evidence on cigarette nicotine reduction with concurrent access to an e-cigarette: Manipulating cigarette nicotine content, e-liquid nicotine content, and e-liquid flavor availability

The reinforcing characteristics of e-cigarettes could moderate the impact of reducing cigarette nicotine content. In this study, people who smoke daily were recruited from North Carolina and Pennsylvania (US) in 2018 and 2019. Within a randomized 2 × 2 × 2 factorial design, participants received investigational cigarettes and an e-cigarette for 12 weeks. Cigarette nicotine content was very low (0.4 mg/g of tobacco; VLNC) or normal (15.8 mg/g; NNC). E-liquids were 0.3% (“low”) or 1.8% (“moderate”) freebase nicotine, and available in tobacco flavors or tobacco, fruit, dessert and mint flavors. Study recruitment concluded before reaching the planned sample size (N = 480). Fifty participants were randomized and 32 completed the study. We found that randomization to VLNC, relative to NNC cigarettes, reduced self-reported cigarettes per day (CPD; mean difference: -12.96; 95% CI: −21.51, −4.41; p = 0.005); whereas e-liquid nicotine content and flavor availability did not have significant effects. The effect of cigarette nicotine content was larger in the moderate vs. low nicotine e-liquid groups and in the all flavors versus tobacco flavors e-liquid groups; tests of the interaction between e-liquid characteristics and cigarette nicotine content were not significant. Biomarkers of smoke exposure at Week 12 did not differ across conditions, which may reflect variability in adherence to only using VLNC cigarettes. In conclusion this study offers preliminary evidence that the extent to which cigarette nicotine reduction decreases smoking may depend on the reinforcing characteristics of alternative products, including the available nicotine contents and flavors of e-cigarettes.

A determination of the aerosolization efficiency of drugs of abuse in a eutectic mixture with nicotine in electronic cigarettes

Characterize the effects of drug interactions with nicotine in the electronic cigarette (e-cigarette). E-liquids are composed of vegetable glycerin (VG), propylene glycol (PG), an active ingredient such as nicotine, and flavorings (Mulder, H.A., et al., Sci Rep., 2019, 9, 102201). Users can adulterate e-liquids with other pharmacologically active substances (Varlet, V. Toxics, 2016, 4, 29). The interaction between the diluent and nicotine forms a eutectic mixture, reducing the melting point to a temperature lower than the individual compounds and promoting aerosolization of the drugs (Gala, U., et al. J Dev Drugs., 2013, 2, e130). The purpose of this study was to evaluate the effect of nicotine on the aerosolization efficiency and recovery of methadone and cocaine using an aerosol capture method adopted from the established Cooperation Centre for the Scientific Research Relative to Tobacco (CORESTA) E-cigarette Task Force industry method. Individual e-liquids were prepared with 12 mg/mL nicotine, methadone, and cocaine in 1:1 PG:VG and drug-free. Aerosol capture was performed using parameters adopted from the CORESTA method. The puff profile was an inhale duration of 3 seconds, an exhale duration of 10 seconds, and a puff volume of 60 mL for a total of 15 puffs. A method for quantitation was validated on a Gas Chromatograph-Mass Spectrometer over five days. The linear range for nicotine was determined to be 500–20,000 ng/mL. Bias and precision were evaluated using quality controls prepared at 1500, 8000, and 16,000 ng/mL. The linear range for methadone and cocaine was 50–5000 ng/mL. Bias and precision were evaluated using quality controls prepared at 150, 1500, and 4000 ng/mL. Carryover was determined for all compounds by evaluating a blank after the injection of the highest calibrator. Aerosol samples were analyzed for drug recovery and dose. Samples were also evaluated for the pyrolytic products of nicotine, methadone, and cocaine: β-nicotyrine (nicotine), EDDP (methadone), and benzoic acid and anhydroecgonine methyl ester (cocaine). The average linear regression ( n = 5) for nicotine, methadone, and cocaine had an r2 > 0.996. Bias and precision for all analytes were within ± 9% and ± 12%CV, respectively. No carryover was observed. In the single drug e-liquids prepared at 12 mg/mL ( n = 3), 1.6 ± 0.2 mg of nicotine, 2.7 ± 0.1 mg of methadone, and 0.94 ± 0.04 mg of cocaine were aerosolized. In the nicotine/methadone mixture ( n = 3), nicotine and methadone increased to 3.7 ± 0.5 mg and 3.7 ± 0.1 mg, respectively. In the nicotine/cocaine mixture ( n = 3), nicotine and cocaine increased to 5.7 ± 2 mg and 2.7 ± 0.2 mg, respectively. In the 15 puffs of the nicotine, methadone, and cocaine e-liquids, 0.22 ± 0.02 g, 0.31 ± 0.01 g, and 0.15 ± 0.02 g ( n = 3) were aerosolized, respectively. In the nicotine/methadone mixture, 0.37 ± 0.01 g ( n = 3) of e-liquid was aerosolized. In the nicotine/cocaine mixture, 0.38 ± 0.02 g ( n = 3) was aerosolized. Pyrolytic products were identified in the e-liquids and aerosol samples, and therefore were not a result of aerosolization. E-liquids containing nicotine and other drugs create a eutectic mixture and can increase the amount of drug delivered in the aerosol. Increases in dose from combining drugs in an e-liquid may result in adverse reactions. The formation of pyrolytic products did not impact the aerosolization efficiency of the parent drugs; however, their presence may cause unexpected effects. The eutectic mixture can result in an increase in aerosolized drug doses.

A determination of the aerosolization efficiency of drugs of abuse in a eutectic mixture with nicotine in electronic cigarettes.

Eutectic mixtures can be formed by adding drugs other than nicotine (DOTNs) to nicotine-based e-liquids in electronic cigarettes (e-cigarettes). Thus, the interaction between nicotine e-liquids and DOTNs must be evaluated. Presented is the change in e-cigarette aerosolization of nicotine and methadone alone versus a 1:1 nicotine:methadone mixture to evaluate the possible formation of a eutectic mixture that can result in an increase of drug delivery. E-liquids were prepared in-house using 1:1 propylene glycol (PG):vegetable glycerin (VG) as a base plus nicotine, methadone hydrochloride, or 1:1 nicotine:methadone hydrochloride. The e-liquids were aerosolized via an automated vaping machine using parameters adopted from the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) E-cigarette Task Force method. Drug recovery was determined by capturing the aerosol from 15 puffs generated by the e-cigarette. Concentrations of nicotine and methadone aerosolized were determined by gas chromatography-mass spectrometry using nicotine (n = 3), methadone (n = 3), and combined nicotine/methadone e-liquids (n = 3), each prepared in-house at 12 mg/ml. The concentration of nicotine and methadone in 15 puffs of the single drug e-liquids were determined to be 1.60 ± 0.20 and 2.67 ± 0.12 mg, respectively. The concentration of nicotine and methadone in 15 puffs of the multidrug e-liquid were determined to be 3.66 ± 0.49 and 3.65 ± 0.10mg, respectively. The single nicotine and methadone e-liquids had recoveries of 70 ± 0.1% and 84 ± 0.1%, respectively. In the 1:1 mixture, the recovery of both drugs increased. The development of a eutectic mixture can promote aerosolization of the drug and deliver a greater dose to the user.

Puffing topography and mouth level exposure of two closed-system Vype e-cigarettes

&lt;p&gt;E-cigarettes have the potential to reduce the harm caused by cigarette smoking; however, product likeability and product satisfaction are important in encouraging smokers to switch to less harmful products. Actual use studies play a key part in evaluating the reduced risk potential of tobacco and nicotine products. User’s puffing behaviour, including puff duration and sensory effects were evaluated for two types of e-cigarette device: a coil-and-wick ‘pen-type’ device (Vype ePen3), and a ceramic block-and-plate ‘pod-type’ device (Vype ePod) with 18 mg/ml nicotine e-liquid. Puffing topography was recorded for these devices with two groups (n=52 each) of adult regular vapers (age 21-64 years) following a fixed 10 puffs protocol where subjects vaped through a special holder attached to a puffing analyser. The sensory characteristics of the aerosol were evaluated using a questionnaire. Mean puff volume was significantly greater (p≤0.0001) for ePen3 than for ePod (79.8 vs 49.4 ml), while puff duration and puff interval were similar (2.13 vs 2.29 s and 8.9 vs 10.3 s, respectively). Notably, MLE to aerosol and nicotine from ePen3 and ePod were similar (3.89 vs 4.80 mg and 0.06 vs 0.07 mg respectively) despite of very different designs of the devices. Participants reported similar overall likeability and other sensory scores for ePen3 and ePod. In summary, the puffing topography attributes support the CORESTA recommended method no. 81, (CRM81) puffing regime, used for &lt;em&gt;in vitro&lt;/em&gt; and chemical analysis. The MLE to nicotine per session from both the products were lower than a typical 6 mg cigarette.&lt;/p&gt;

A pilot randomised controlled trial of abrupt versus gradual smoking cessation in combination with vaporised nicotine products for people receiving alcohol and other drug treatment

BackgroundVaporised nicotine products (VNPs) may be a potential quit smoking strategy. Most research has permitted participants to use VNPs ad libitum. This is the first study to examine combining the use of a VNP with a gradual or abrupt cessation guideline. This study aims to test the potential feasibility of a quit smoking strategy (abrupt verses gradual cessation) in combination with vaporised nicotine products among people in AOD treatment. MethodsWe conducted a pilot randomised controlled trial between April 2018 and July 2019. Participants were recruited from AOD programs located within one area health service in Australia. Participants were provided with two VNPs, a 12-week supply of nicotine e-liquid and randomised to either the abrupt (assigned a quit date the day they were provided their VNP) or gradual quit smoking strategy (reduce baseline number of cigarettes per day by 25% over a 4 week period), no further behavioral support was provided. Feasibility was assessed through successful recruitment rates, retention, and adherence to study conditions. Participant perceived helpfulness and satisfaction assessed acceptability. ResultsAmong 80 interested individuals, 66 were eligible and consented (100% recruitment rate). From the 66 participants that consented and completed the baseline survey, 60 received the intervention assigned at a 1:1 ratio with 30 in the gradual cessation and 30 in the abrupt cessation group. Retention was 86.4% (n = 52) at 12-weeks post-intervention commencement. Ninety-six percent (n = 25) of participants in the gradual and 95.8% (n = 23) of participants in the abrupt group were using the VNPs at 12-weeks (p = 0.66). There was no difference in adherence to the assigned quit plan between gradual cessation 44% (n = 11) and abrupt cessation 71% (n = 17) groups (p = 0.117). Median perceived helpfulness of VNPs was high for both gradual (10/10) and abrupt (9/10) groups (p = 0.813). Similarly, median perceived satisfaction of VNPs was high for both gradual (9 /10) and abrupt (8/10) groups (p = 0.414). ConclusionsAOD participants found an intervention that involved VNPs to be satisfying and helpful. Future large scale trials are needed to elucidate whether a gradual or abrupt cessation guideline is more beneficial in main a quit attempt with a VNP.