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INTRODUCTION: Popular pod-style e-cigarettes commonly use nicotine salt-based e-liquids that cause less irritation when inhaled and can deliver higher nicotine concentrations than free-base nicotine. This study investigated the pharmacokinetic and pharmacodynamic effects of different nicotine formulations (salt vs. free-base) and concentrations that might influence systemic nicotine absorption and appeal of e-cigarettes. AIMS AND METHODS: In this randomized, double-blind, within-subject crossover study, 20 non-nicotine-naïve participants were switched among three e-liquids (free-base nicotine 20 mg/mL, nicotine salt 20 mg/mL, nicotine salt 40 mg/mL) using a refillable pod system and a standardized vaping protocol (one puff every 30 seconds, 10 puffs total). Serum nicotine concentrations and vital signs were assessed over 180 minutes; direct effects, craving, satisfaction, withdrawal, and respiratory symptoms were measured using questionnaires. CYP2A6 genotypes and the nicotine metabolite ratio were also assessed. RESULTS: Eleven (55%) participants were male and the median age was 23.5 years (range 18-67). All three formulations differed significantly in peak serum nicotine concentration (baseline adjusted Cmax, median (range): 12.0 ng/mL (1.6-27.3), 5.4 ng/mL (1.9-18.7), and 3.0 ng/mL (1.3-8.8) for nicotine salt 40 mg/mL, nicotine salt 20 mg/mL and free-base 20 mg/mL, respectively). All groups reached Cmax 2.0-2.5 minutes (median) after their last puff. Differences in subjective effects were not statistically significant. No serious adverse events were observed. CONCLUSIONS: Free-base 20 mg/mL formulations achieved lower blood nicotine concentrations than nicotine salt 20 mg/mL, while 40 mg/mL nicotine salt yielded concentrations similar to cigarette smoking. The findings can inform regulatory policy regarding e-liquids and their potential use in smoking cessation. IMPLICATIONS: Nicotine salt formulations inhaled by an e-cigarette led to higher nicotine delivery compared to nicotine-free-base formulations with the same nicotine concentration. These findings should be considered in future regulatory discussions. The 40 mg/mL nicotine salt formulation showed similar nicotine delivery as combustible cigarettes, albeit at concentrations over the maximum limit for e-liquids allowed in the European Union. Nicotine delivery resembling combustible cigarettes might be beneficial for smokers willing to quit to adequately alleviate withdrawal symptoms. However, increased nicotine delivery can also pose a public health risk, raising concerns about abuse liability, especially among youth and nonsmokers.

Background and purposeTraumatic brain injury (TBI) causes lifelong physical and psychological dysfunction in affected individuals. The current study investigated the effects of chronic nicotine exposure via E-cigarettes (E-cig) (vaping) on TBI-associated behavioural and biochemical changes.Experimental approachAdult C57/BL6J male mice were subjected to controlled cortical impact (CCI) followed by daily exposure to E-cig vapour for 6 weeks. Sensorimotor functions, locomotion, and sociability were subsequently evaluated by nesting, open field, and social approach tests, respectively. Immunoblots were conducted to examine the expression of mature brain-derived neurotrophic factor (mBDNF) and associated downstream proteins (p-Erk, p-Akt). Histological analyses were performed to evaluate neuronal survival and neuroinflammation.Key resultsPost-injury chronic nicotine exposure significantly improved nesting performance in CCI mice. Histological analysis revealed increased survival of cortical neurons in the perilesion cortex with chronic nicotine exposure. Immunoblots revealed that chronic nicotine exposure significantly up-regulated mBDNF, p-Erk and p-Akt expression in the perilesion cortex of CCI mice. Immunofluorescence microscopy indicated that elevated mBDNF and p-Akt expression were mainly localized within cortical neurons. Immunolabelling of Iba1 demonstrated that chronic nicotine exposure attenuated microglia-mediated neuroinflammation.Conclusions and implicationsPost-injury chronic nicotine exposure via vaping facilitates recovery of sensorimotor function by upregulating neuroprotective mBDNF/TrkB/Akt/Erk signalling. These findings suggest potential neuroprotective properties of nicotine despite its highly addictive nature. Thus, understanding the multifaceted effects of chronic nicotine exposure on TBI-associated symptoms is crucial for paving the way for informed and properly managed therapeutic interventions.

ObjectiveTo describe how young adults use electronic cigarettes (electronic nicotine delivery systems (ENDS)) for smoking cessation and reasons why they may or may not successfully quit smoking.MethodsLongitudinal qualitative data were collected annually from 2017 to 2019 for 25 young adult tobacco users (aged 18-29 years) in California (USA) who used ENDS to quit/reduce smoking. Thematic and trajectory analyses were used to identify key within-person and between-person changes in tobacco/nicotine use over time.ResultsFive types of tobacco use transition were identified among baseline dual users of cigarettes and ENDS: sustained dual use without reduced smoking (n=8), transition to exclusive daily ENDS use (n=6), sustained dual use with reduced smoking (n=5), transition back to exclusive smoking (n=4) and transition to neither smoking nor vaping (n=2). Participants' ENDS use behaviour varied over time in terms of vaping quantity and device characteristics (eg, changing nicotine concentrations/flavours, switching between multiple devices). Three themes that related to successfully replacing cigarettes with ENDS were perceived positive physical effects, perceived satisfaction and enjoyment and context changes. Four themes for unsuccessful replacement were perceived negative physical discomforts, perceived addictiveness and harm, unsatisfactory substitution for cigarettes and device malfunction.ConclusionsYoung adults' experiences with using ENDS as a smoking cessation aid were highly variable. Adequate nicotine delivery and perceived safety and benefits contributed to successfully reducing or quitting cigarettes. Providing behavioural counselling and standardising ENDS products may enhance cessation for young adults.