Project description:Reducing the negative health effects caused by tobacco products continues to be a public health priority. The Family Smoking Prevention and Tobacco Control Act of 2009 gives the Food Drug Administration authority to pursue several new strategies, including regulating levels of nicotine and other ingredients in tobacco products. A nicotine reduction strategy proposed by Benowitz and Henningfield aims to reduce the nicotine content of tobacco products to an amount below a threshold that supports neither the development nor maintenance of addiction. Many factors must be considered to determine the viability and efficacy of this approach. For example, the policy should be based on precise information on the dose-dependent effects of nicotine on reinforcement and factors that contribute to individual differences in these effects. However, there have been few studies on these topics in humans. Here, we briefly review nicotine pharmacology and reinforcement then present several studies illustrating the application of intravenous (IV) nicotine delivery to study nicotine reinforcement in humans. We discuss how nicotine delivery by IV infusion may be uniquely suited for studying nicotine's dose-dependent effects, and how this can inform tobacco regulatory science to facilitate the development of effective tobacco control policies.
Project description:IntroductionScientific discoveries over the past few decades have provided significant insight into the abuse liability and negative health consequences associated with tobacco and nicotine-containing products. While many of these advances have led to the development of policies and laws that regulate access to and formulations of these products, further research is critical to guide future regulatory efforts, especially as novel nicotine-containing products are introduced and selectively marketed to vulnerable populations.DiscussionIn this narrative review, we provide an overview of the scientific findings that have impacted regulatory policy and discuss considerations for further translation of science into policy decisions. We propose that open, bidirectional communication between scientists and policy makers is essential to develop transformative preventive- and intervention-focused policies and programs to reduce appeal, abuse liability, and toxicity of the products.ConclusionsThrough these types of interactions, collaborative efforts to inform and modify policy have the potential to significantly decrease the use of tobacco and alternative nicotine products and thus enhance health outcomes for individuals.ImplicationsThis work addresses current topics in the nicotine and tobacco research field to emphasize the importance of basic science research and provide examples of how it can be utilized to inform public policy. In addition to relaying current thoughts on the topic from experts in the field, the article encourages continued efforts and communication between basic scientists and policy officials.
Project description:Over the past 20 years, a series of reports written by groups of senior researchers and administrators have recommended changes to improve the training environments for graduate students and postdoctoral researchers in the United States. However, academic institutions and departments have largely failed to implement these recommendations, which has exacerbated the problems faced by these trainees. Here, based on input from trainees at different career stages, we outline seven practical changes that academic institutions and departments can make to improve their training environments.
Project description:Traditional breeding and molecular approaches have been used to develop tobacco varieties with reduced nicotine and secondary alkaloid levels. However, available low-alkaloid tobacco varieties have impaired leaf quality likely due to the metabolic consequences of nicotine biosynthesis downregulation. Recently, we found evidence that the unbalanced crosstalk between nicotine and polyamine pathways is involved in impaired leaf ripening of a low-alkaloid (LA) Burley 21 line having a mutation at the Nic1 and Nic2 loci, key biosynthetic regulators of nicotine biosynthesis. Since the Nic1 and Nic2 loci are comprised of several genes, all phenotypic changes seen in LA Burley 21 could be due to a mixture of genetics-based responses. Here, we investigated the commercial burley variety TN90 LC and its transgenic versions with only one downregulated gene, either putrescine methyl transferase (PMT-RNAi) or PR50-protein (PR50-RNAi). Nicotine levels of cured lamina of TN90 LC, TN90 PMT-RNAi and TN90 PR50-RNAi, were 70.5 ± 3.8, 2.4 ± 0.5, and 6.0 ± 1.1 mg/g dry weight, respectively. Low-alkaloid transgenic lines showed delayed leaf maturation and impaired leaf quality. We analyzed polyamine contents and ripening markers in wild-type TN90 control plants (WT) and the two transgenic lines. The ripening markers revealed that the PMT-RNAi line showed the most pronounced impaired leaf maturation phenotype at harvest, characterized by higher chlorophyll (19%) and glucose (173%) contents and more leaf mesophyll cells per area (25%), while the ripening markers revealed that maturation of PR50-RNAi plants was intermediate between PMT-RNAi and WT lines. Comparative polyamine analyses showed an increase in free and conjugated polyamines in roots of both transgenic lines, this being most pronounced in the PMT-RNAi plants. For PMT-RNAi plants, there were further perturbations of polyamine content in the leaves, which mirrored the general phenotype, as PR50-RNAi transgenic plants looked more similar to the WT than PMT-RNAi transgenic plants. Activity of ornithine decarboxylase, the enzyme that catalyzes the committing step of polyamine biosynthesis, was significantly higher in roots and mature leaves of PMT-RNAi plants in comparison to WT, while there was no increase observed for arginine decarboxylase. Treatment of both transgenic lines with polyamine biosynthesis inhibitors decreased the polyamine content and ameliorated the phenotype, confirming the intricate interplay of polyamine and nicotine biosynthesis in tobacco and the influence of this interplay on leaf ripening.
Project description:Tobacco smoking is globally far more widespread than use of any other substance of abuse. Nicotine is an important tobacco constituent that is responsible for addictive properties of smoking. The currently available medications for the treatment of nicotine addiction have limited efficacy. A challenging novel therapeutic concept is vaccination against nicotine. An efficient vaccine would generate antibodies that sequester nicotine in the blood and prevent its access to the brain. The vaccine would have great potential for treating nicotine addiction and for relapse prevention. We reviewed the current status of vaccines against nicotine addiction that are undergoing clinical trials or are in preclinical development. We discuss problems associated with the development of nicotine vaccines, their efficacy in addiction treatment, challenges and ethical concerns. Existing evidence indicates that nicotine vaccination is well tolerated and capable of inducing an immune response but its effectiveness in increasing smoking abstinence has not been shown so far.
Project description:BackgroundWhile much is known about the demand for conventional cigarettes, little is known about the determinants of demand for electronic nicotine delivery systems (ENDS or e-cigarettes). The goal of this study is to estimate the own and cross-price elasticity of demand for e-cigarettes and to examine the impact of cigarette prices and smoke-free policies on e-cigarette sales.MethodsQuarterly e-cigarette prices and sales and conventional cigarette prices from 2009 to 2012 were constructed from commercial retail store scanner data from 52 U.S. markets, for food, drug and mass stores, and from 25 markets, for convenience stores. Fixed-effects models were used to estimate the own and cross-price elasticity of demand for e-cigarettes and associations between e-cigarette sales and cigarette prices and smoke-free policies.ResultsEstimated own price elasticities for disposable e-cigarettes centred around -1.2, while those for reusable e-cigarettes were approximately -1.9. Disposable e-cigarette sales were higher in markets where reusable e-cigarette prices were higher and where less of the population was covered by a comprehensive smoke-free policy. There were no consistent and statistically significant relationships between cigarette prices and e-cigarette sales.ConclusionsE-cigarette sales are very responsive to own price changes. Disposable e-cigarettes appear to be substitutes for reusable e-cigarettes. Policies increasing e-cigarette retail prices, such as limiting rebates, discounts and coupons and imposing a tax on e-cigarettes, could potentially lead to significant reductions in e-cigarette sales. Differential tax policies based on product type could lead to substitution between different types of e-cigarettes.
Project description:Cigarette smoking is increasingly concentrated among marginalized populations with limited access to evidence-based cessation treatment. This includes racial/ethnic minorities, lower income individuals, those with lower educational attainment, and residents of rural areas. To reach Healthy People 2020 objectives, successful cessation interventions must narrow these disparities. Nicotine replacement therapy (NRT) sampling is an easily translatable and scalable intervention that could enhance treatment access and thus narrow disparities. The present study examined individual-level demographic moderators of the impact of NRT sampling on cessation-related behaviors including: 1) use of a cessation medication, 2) making a 24-hour quit attempt, 3) floating abstinence, and 4) 7-day point prevalence abstinence at 6-months. Study participants included N = 1245 adult smokers enrolled in the Tobacco Intervention in Primary Care Treatment Opportunities for Providers (TIP TOP) study, a recently concluded large-scale clinical trial of NRT sampling relative to standard care within 22 primary care clinics across South Carolina. Generalized linear models examined individual-level demographic moderators of treatment effect. Results suggest that NRT sampling may be more effective among some of the most disadvantaged groups of smokers, including smokers with lower income and education, as well those who live in more rural areas. The effects of NRT sampling did not differ by race. In sum, NRT sampling is a low-cost, low-burden intervention that could be disseminated broadly to reach large numbers of smokers and potentially narrow cessation disparities.
Project description:According to the 'hardening hypothesis', average nicotine dependence will increase as less dependent smokers quit relatively easily in response to effective public health interventions, so that sustained progress in reducing smoking prevalence will depend on shifting the emphasis of tobacco control programs towards intensive treatment of heavily dependent smokers (who comprise an increasing fraction of continuing smokers). We used a system dynamics model of smoking behaviour to explore the potential for hardening in a population of smokers exposed to effective tobacco control measures over an extended period. Policy-induced increases in the per capita cessation rate are shown to lead inevitably to a decline in the proportion of smokers who are heavily dependent, contrary to the hardening hypothesis. Changes in smoking behaviour in Australia over the period 2001‒2016 resulted in substantial decreases in current smoking prevalence (from 23.1% in 2001 to 14.6% in 2016) and the proportion of heavily dependent smokers in the smoking population (from 52.1% to 36.9%). Public health interventions that have proved particularly effective in reducing smoking prevalence (tobacco tax increases, smoke-free environment legislation, antismoking mass media campaigns) are expected to also contribute to a decline in population-level nicotine dependence.
Project description:Most people start experimenting with tobacco products or e-cigarettes in early adolescence and become habitual smokers in late adolescence or adulthood. These studies investigated if exposure to tobacco smoke or nicotine during early and mid-adolescence affects nicotine intake in late adolescence and early adulthood. Male and female rats were exposed to tobacco smoke from low- and high-nicotine SPECTRUM cigarettes or nicotine (0.3 mg/kg, twice a day) from postnatal day (P) 24-42. The self-administration sessions started at P55. The rats self-administered nicotine for 14-15 days under a fixed-ratio 1 schedule, and on the first day, the maximum number of infusions was twenty. Exposure to smoke from high, but not low, nicotine cigarettes during adolescence increased nicotine self-administration in female but not male rats. Adolescent treatment with nicotine facilitated nicotine self-administration. On the first day of nicotine self-administration, nicotine-treated rats reached the maximum number of infusions before the saline-treated control rats. Nicotine intake was also higher in the nicotine-treated female rats than in the saline-treated females. There was no sex difference in nicotine intake in controls when the data from the studies were combined. Smoke exposure led to a dose-dependent increase in plasma nicotine and cotinine levels in adolescent rats. Exposure to smoke from high-nicotine cigarettes and 0.3 mg/kg of nicotine led to plasma nicotine and cotinine levels that are similar to those in tobacco users. These findings indicate that in females, but not males, exposure to nicotine during adolescence may facilitate smoking and e-cigarette use later in life.
Project description:An effective plant alkaloid chemical defense requires a variety of transport processes, but few alkaloid transporters have been characterized at the molecular level. Previously, a gene fragment encoding a putative plasma membrane proton symporter was isolated, because it was coordinately regulated with several nicotine biosynthetic genes. Here, we show that this gene fragment corresponds to a Nicotiana tabacum gene encoding a nicotine uptake permease (NUP1). NUP1 belongs to a plant-specific class of purine uptake permease-like transporters that originated after the bryophytes but before or within the lycophytes. NUP1 expressed in yeast cells preferentially transported nicotine relative to other pyridine alkaloids, tropane alkaloids, kinetin, and adenine. NUP1-GFP primarily localized to the plasma membrane of tobacco Bright Yellow-2 protoplasts. WT NUP1 transcripts accumulated to high levels in the roots, particularly in root tips. NUP1-RNAi hairy roots had reduced NUP1 mRNA accumulation levels, reduced total nicotine levels, and increased nicotine accumulation in the hairy root culture media. Regenerated NUP1-RNAi plants showed reduced foliar and root nicotine levels as well as increased seedling root elongation rates. Thus, NUP1 affected nicotine metabolism, localization, and root growth.