The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review.

INTRODUCTION: Many adult cigarette smokers use electronic cigarettes (e-cigarettes) to cut down on or quit smoking cigarettes. E-cigarettes with higher abuse potential and appeal might facilitate complete switching. E-liquid nicotine concentration and flavor are two of the characteristics that may affect the abuse potential and appeal of e-cigarettes. The objective of this systematic review was to compile results from survey, animal, human laboratory, and clinical studies to understand the possible effects of nicotine concentration and flavor on abuse potential and appeal of e-cigarettes in adult current and former cigarette and e-cigarette users. AIMS AND METHODS: A comprehensive literature search was conducted in Ovid Medline and PsycINFO followed by citation tracking in Web of Science Core Collection. Peer-reviewed studies published in English between 2007 and August 2020 were selected that analyzed differences between e-liquid nicotine concentration and/or flavors, had outcome measures related to abuse potential and/or appeal, and included adult humans (18+) or animals. A total of 1624 studies were identified and screened. A qualitative synthesis of results was performed. RESULTS: Results from 104 studies included in this review suggest that higher nicotine concentration and access to a variety of flavors are likely to be associated with higher abuse potential and appeal of e-cigarettes for adult current and former cigarette and e-cigarette users. CONCLUSIONS: Higher nicotine concentrations and the availability of a variety of flavors in e-cigarettes might facilitate complete substitution for cigarettes. Future e-cigarette regulations should take into account their impact on smokers, for whom e-cigarettes may be a cessation tool or reduced-harm alternative. IMPLICATIONS: E-cigarettes may provide a reduced-harm alternative to cigarettes for smokers unwilling/unable to quit or serve as a path for quitting all nicotine products. Higher nicotine concentrations and flavor variety are associated with higher abuse potential and appeal of e-cigarettes. Higher abuse potential and appeal products may help facilitate complete switching from cigarettes to e-cigarettes. Regulation of nicotine concentration and flavors aimed at decreasing naïve uptake may inadvertently decrease uptake and complete switching among smokers, reducing the harm reduction potential of e-cigarettes. Evidence-based effects of regulating nicotine concentration and flavors must be considered for the population as a whole, including smokers.

Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the dorsomedial prefrontal cortex of male and female rats.

BACKGROUND: Opioid abuse is a chronic disorder likely involving stable neuroplastic modifications. While a number of molecules contributing to these changes have been identified, the broader spectrum of genes and gene networks that are affected by repeated opioid administration remain understudied. METHODS: We employed Next-Generation RNA-sequencing (RNA-seq) followed by quantitative chromatin immunoprecipitation to investigate changes in gene expression and their regulation in adult male and female rats' dorsomedial prefrontal cortex (dmPFC) after a regimen of daily injection of morphine (5.0 mg/kg; 10 days). Ingenuity Pathway Analysis (IPA) was used to analyze affected molecular pathways, gene networks, and associated regulatory factors. A complementary behavioral study evaluated the effects of the same morphine injection regimen on locomotor activity, pain sensitivity, and somatic withdrawal signs. RESULTS: Behaviorally, repeated morphine injection induced locomotor hyperactivity and hyperalgesia in both sexes. 90 % of differentially expressed genes (DEGs) in morphine-treated rats were upregulated in both males and females, with a 35 % overlap between sexes. A substantial number of DEGs play roles in synaptic signaling and neuroplasticity. Chromatin immunoprecipitation revealed enrichment of H3 acetylation, a transcriptionally activating chromatin mark. Although broadly similar, some differences were revealed in the gene ontology networks enriched in females and males. CONCLUSIONS: Our results cohere with findings from previous studies based on a priori gene selection. Our results also reveal novel genes and molecular pathways that are upregulated by repeated morphine exposure, with some common to males and females and others that are sex-specific.

The role of subjective responses in electronic cigarette uptake and substitution in adult smokers.

BACKGROUND: While a majority of cigarette smokers who use electronic cigarettes (e-cigarettes) choose to continue using cigarettes, completely switching to e-cigarettes is necessary to reduce tobacco-related harm. Whether specific subjective responses to e-cigarettes are associated with extent of smoking reduction and complete switching from cigarettes to e-cigarettes is unclear. This study determined whether initial subjective responses to e-cigarettes related to the successful substitution of e-cigarettes for cigarettes and extent of cigarette and e-cigarette use. METHODS: Adult cigarette smokers (N = 58) uninterested in quitting were asked to completely substitute their cigarettes with an e-cigarette (Vuse Solo) for 8 weeks. At week 1, subjective responses to e-cigarettes were measured using the Product Evaluation Scale and Drug Effects/Liking Survey. A Poisson regression examined whether any of these initial subjective responses were associated with smoke-free days, e-cigarette puffs, and cigarettes smoked between weeks 6 and 8 after adjustment for potential confounders. A logistic regression examined the relationship between subjective measures and exhaled carbon monoxide (CO) verified 7-day abstinence at week 8 after adjustment for potential confounders. RESULTS: Following Holm's p-value adjustment, e-cigarette liking and desire were associated with increased e-cigarette use (adjusted p < 0.01) and decreased cigarette use (adjusted p < 0.05). Measures of psychological reward and drug liking were associated with 7-day abstinence, however this association was no longer significant following p-value adjustment. CONCLUSIONS: Initial subjective responses were related to cigarette and e-cigarette use at weeks 6-8, but not smoke-free days or CO-verified 7-day abstinence.