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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.

Our purpose was to test the hypothesis that ultrasonic cigarettes (u-cigarettes), which operate at relatively low temperatures, produce aerosols that are less harmful than heated-coil pod-style electronic cigarettes (e-cigarettes). The major chemicals in SURGE u-cigarette fluids and aerosols were quantified, their cytotoxicity and cellular effects were assessed, and a Margin of Exposure risk assessment was performed on chemicals in SURGE fluids. Four SURGE u-cigarette flavor variants (Blueberry Ice, Watermelon Ice, Green Mint, and Polar Mint) were evaluated. Flavor chemicals were quantified in fluids and aerosols using gas chromatography/mass spectrometry. Cytotoxicity and cell dynamics were assessed using the MTT assay, live-cell imaging, and fluorescence microscopy. WS-23 (a coolant) and total flavor chemical concentrations in SURGE were similar to e-cigarettes, while SURGE nicotine concentrations (13-19 mg/mL) were lower than many fourth generation e-cigarettes. Transfer efficiencies of dominant chemicals to aerosols in SURGE ranged from 44-100%. SURGE fluids and aerosols had four dominant flavor chemicals (>1 mg/mL). Toxic aldehydes were usually higher in SURGE aerosols than in SURGE fluids. SURGE fluids and aerosols had aldehyde concentrations significantly higher than pod-style e-cigarettes. Chemical constituents, solvent ratios, and aldehydes varied among SURGE flavor variants. SURGE fluids and aerosols inhibited cell growth and mitochondrial reductases, produced attenuated and round cells, and depolymerized actin filaments, effects that depended on pod flavor, chemical constituents, and concentration. The MOEs for nicotine, WS-23, and propylene glycol were

BACKGROUND: More people who smoke and are living with HIV now die from tobacco-related diseases than HIV itself. Most people are ambivalent about quitting smoking and want to quit someday but not yet. Scalable, effective interventions are needed to motivate and support smoking cessation among people ambivalent about quitting smoking (PAQS) who are living with HIV. OBJECTIVE: This study aims to develop an app-based intervention for PAQS who are living with HIV and assess its feasibility, acceptability, and potential impact. Results of this study will inform plans for future research and development. METHODS: In phase 1, PAQS living with HIV (n=8) participated in user-centered design interviews to inform the final intervention app design and recruitment plan for a subsequent randomized pilot study. In phase 2, PAQS living with HIV were randomized to either a standard care control app or a similar experimental app with additional content tailored for PAQS and those with HIV. Participants were followed for 3 months. Feasibility focused on recruitment, retention, and participants willingness to install the app. The study was not powered for statistical significance. Indices of acceptability (satisfaction and use) and impact (smoking behavior change and treatment uptake) were assessed via automated data and self-report among those who installed and used the app (n=19). RESULTS: Recruitment for both study phases was a challenge, particularly via web-based and social media platforms. Enrollment success was greater among people living with HIV recruited from a health care provider and research registry. Once enrolled, retention for the phase 2 randomized study was good; 74% (14/19) of the participants completed the 3-month follow-up. Phase 1 findings suggested that PAQS living with HIV were receptive to using an app-based intervention to help them decide whether, when, and how to stop smoking, despite not being ready to quit smoking. Phase 2 findings further supported this conclusion based on feedback from people who agreed to use an app, but group differences were observed. Indices of acceptability favored the experimental arm, including a descriptively higher mean number of sessions and utilization badges. Similarly, indices of potential impact were descriptively higher in the experimental arm (proportion reducing smoking, making a quit attempt, or calling free tobacco quitline). No participants in either arm quit smoking at the 3-month follow-up. CONCLUSIONS: On the basis of this formative work, PAQS living with HIV may be receptive to using a mobile health-based app intervention to help them decide whether, when, or how to stop using tobacco. Indices of acceptability and impact indicate that additional research and development are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05339659; https://clinicaltrials.gov/study/NCT05339659.

BACKGROUND: Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems. METHODS: In a U.S. six-site, open-label, parallel-arm study, smokers were randomized for twelve weeks to an experimental marketplace containing cigarettes with either 0.4 mg or 15.8 mg nicotine per gram of tobacco; all had access to non-combusted alternative nicotine delivery systems (e.g., e-cigarettes; medicinal nicotine). Group differences in the primary outcomes (cigarettes per day, number of smoke-free days) were examined using linear and negative binomial regression, respectively (Trial Registration: NCT03272685). FINDINGS: Among 438 randomized participants (mean [standard deviation (SD), range] age, 44.5 [11.9, 20-73] years, 225 [51.4%] women, 282 [64.4%] White and 339 [77.4%] trial completers), those in the 0.4 mg vs. 15.8 mg nicotine cigarette condition experienced significantly lower cigarettes per day at the end of intervention (mean [SD], 7.05 [7.88] vs. 12.95 [9.07], adjusted mean difference, -6.21 [95% CI, -7.66 to -4.75], P

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.

The use of e-cigarettes (vaping) by young adults has increased substantially in the past decade. Although health risks of long-term e-cigarette use remain unknown, there is evidence of acute physiological harms. Most young adults who vape report intent to quit, but little is known about effective interventions. This protocol paper reports on the development and design of a pilot trial of a vaping intervention for young military Veterans. Young adult Veterans accessing VA healthcare (n = 20) who vape daily and have been referred for cessation services will be enrolled. To maximize accessibility the intervention will be delivered virtually; participants will be randomized to receive behavioral counseling by telephone or by video telehealth. The intervention was adapted from an existing program targeting young adult cigarette smokers and will include 6 individual counseling sessions delivered over 8 weeks. Assessment visits will occur at baseline, at end-of-treatment, and 4 weeks later. Analyses will evaluate feasibility and acceptability of the intervention overall, and will compare telephone and video telehealth modalities. Longitudinal regression will be used to evaluate changes in vaping behavior and in nicotine dependence over time. This study will provide assessment of a novel intervention adapted for Veterans who vape nicotine. The comparison of two modalities of virtual intervention delivery will increase knowledge and the potential to disseminate across VA and other healthcare systems. Findings from this pilot trial will inform the design of future, larger studies of vaping cessation interventions for younger Veterans.

IntroductionThere has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood.MethodsMale and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from post-natal day (PND) 31-40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for volitional exposure to nicotine vapor (PND 285-395). Plasma nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session.ResultsGroup mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change the effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG-exposed females to nicotine vapor in a fixed ratio 5 challenge.ConclusionsRepeated adolescent nicotine vapor inhalation leads to enhanced liability for volitional exposure to nicotine vapor in adulthood in female rats, but minimal change in spontaneous locomotor behavior.ImplicationsThese results show that adolescent vaping of nicotine can lead to lasting sensitization to the effects of nicotine in adulthood, including volitional responding for nicotine vapor. Demonstration of this in a controlled animal model establishes causality in a manner not possible from longitudinal evidence in human populations. These findings further highlight the importance of decreasing adolescent nicotine exposure to e-cigarettes to reduce consumption in adulthood.

PurposeCo-use of tobacco and cannabis is a common and complex behavior. The lack of harmonized measures of co-use yields confusion and inconsistencies in synthesizing evidence about the health effects of co-use. We aimed to classify co-use patterns based on temporal proximity and describe preferred products and motives for each pattern in order to improve co-use surveillance.MethodsWe conducted semi-structured interviews in a sample of 34 young adults (Mage = 22.8 years, 32.4 % female) during 2017-2019 in California, USA. We employed a qualitative thematic analysis to identify timing, reasons, and contexts for tobacco and cannabis co-use and classify co-use patterns.ResultsFour emergent patterns of co-use with increasing temporal proximity between tobacco use and cannabis use were: Same-month different-day co-use (Pattern 1); Same-day different-occasion co-use (Pattern 2); Same-occasion sequential co-use (Pattern 3); and Same-occasion simultaneous co-use (Pattern 4). Participants used various product combinations within each pattern. Similar motives for all patterns were socialization, product availability, and coping with stress/anxiety. Unique motive for temporally distant patterns (Patterns 1 and 2) was seeking substance-specific effects (e.g., stimulant effect from nicotine, relaxation effects from cannabis), while unique motives for temporally close patterns (Patterns 3 and 4) were seeking combined effects from both substances (e.g., more intense psychoactive effects, mitigating cannabis adverse effects) and behavioral trigger (e.g., cannabis use triggers tobacco use).ConclusionsOur classification of co-use patterns can facilitate consistency for measuring co-use and assessing its health impacts. Future research should also measure product types and motives for different patterns to inform intervention efforts.