Effectively Regulating E-Cigarettes and Their Advertising—and the First Amendment

If tobacco smoking did not exist in the United States, there would be no reason, from a public health perspective, to allow addictive, nicotine-containing e-cigarettes to be marketed and sold. Because e-cigarette use, by itself, is neither beneficial nor benign to users and nonusers, the only public health justification for allowing e-cigarettes in the existing U.S. market would be if doing so would not sustain or increase existing smoking levels but would help smokers quit completely or provide addicted smokers a less harmful way to obtain the nicotine they crave. Yet e-cigarettes are now pervasive in the U.S. market, being sold with unnecessary harmful characteristics and being advertised in ways that encourage youth experimentation and use. Unless effectively regulated, e-cigarette use will be more harmful than necessary and their advertising will work to: (a) increase initiation among both youth and non-tobacco-using adults; (b) prompt former smokers to relapse back into addicted nicotine use; (c) encourage smokers to use e-cigarettes where they cannot smoke; and (d) prompt smokers to switch to e-cigarettes instead of quitting all tobacco and nicotine use. This paper proposes a viable way to regulate e-cigarettes and their advertising both to minimize the health harms they might cause and to allow e-cigarettes to fulfill their potential as cessation aids or harm-reduction products. Normally, any efforts by FDA to establish effective advertising restrictions must accommodate considerable constraints from the First Amendment’s commercial speech protections. However, because of existing text in the Tobacco Control Act, on the effective date of the final FDA deeming rule that puts e-cigarettes under FDA’s active tobacco product jurisdiction all nicotine-containing e-cigarettes will be on the U.S. market illegally until they can obtain permissive orders from FDA. That situation should reduce applicable First Amendment constraints, providing FDA with a tremendous opportunity to place the kinds of substantial restrictions and requirements on e-cigarette advertising necessary to minimize their harmful aspects and maximize their potential to produce substantial net public health benefits

Expression of a Constitutively Active Nitrate Reductase Variant in Tobacco Reduces Tobacco-Specific Nitrosamine Accumulation in Cured Leaves and Cigarette Smoke

Burley tobaccos (Nicotiana tabacum) display a nitrogen-use-deficiency phenotype that is associated with the accumulation of high levels of nitrate within the leaf, a trait correlated with production of a class of compounds referred to as tobacco-specific nitrosamines (TSNAs). Two TSNA species, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), have been shown to be strong carcinogens in numerous animal studies. We investigated the potential of molecular genetic strategies to lower nitrate levels in burley tobaccos by overexpressing genes encoding key enzymes of the nitrogen-assimilation pathway. Of the various constructs tested, only the expression of a constitutively active nitrate reductase (NR) dramatically decreased free nitrate levels in the leaves. Field-grown tobacco plants expressing this NR variant exhibited greatly reduced levels of TSNAs in both cured leaves and mainstream smoke of cigarettes made from these materials. Decreasing leaf nitrate levels via expression of a constitutively active NR enzyme represents an exceptionally promising means for reducing the production of NNN and NNK, two of the most well-documented animal carcinogens found in tobacco products

The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial

Smoking cessation medications are effective but often underutilised because of costs and side effects. Cytisine is a plant-based smoking cessation medication with over 50 years of use in Central and Eastern Europe. While cytisine has been found to be well-tolerated and more effective than nicotine replacement therapy, direct comparison with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost-effectiveness of cytisine compared with varenicline.Two arm, parallel group, randomised, non-inferiority trial, with allocation concealment and blinded outcome assessment.Australian population-based study.Adult daily smokers (N=1266) interested in quitting will be recruited through advertisements and Quitline telephone-based cessation support services.Eligible participants will be randomised (1:1 ratio) to receive either cytisine capsules (25-day supply) or varenicline tablets (12-week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10-12 minute sessions).Assessments will be undertaken by telephone at baseline, 4- and 7-months post-randomisation. Participants will also be contacted twice (two and four weeks post-randomisation) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self-reported 6-month continuous abstinence from smoking, verified by carbon monoxide at 7-month follow-up. We will also evaluate the relative safety and cost-effectiveness of cytisine compared with varenicline. Secondary outcomes will include self-reported continuous and 7-day point prevalence abstinence and cigarette consumption at each follow-up interview.If cytisine is as effective as varenicline, its lower cost and natural plant-based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives worldwide

Examining The Malleability Of Cigarette Product Preference

Introduction: Cigarette preference increases as a function of nicotine content, but preference can be shifted by manipulating cigarette cost. The aim of the present study is to model whether the behavioral-economic metric of unit price (cigarette cost/nicotine content) accounts for cigarette preference shifts and whether preference changes to very low nicotine content cigarettes (VLNCs) are associated with corresponding changes in smoking rate. Methods: 169 daily smokers from populations vulnerable to smoking completed sessions in which choices between smoking normal nicotine content (NNC) (15.8mg/g) and VLNC (0.4mg/g) cigarettes were concurrently available. In Condition 1, choices for both products were available ad-lib at an equal cost of 10 responses/choice. In Condition 2, VLNCs were again available ad-lib at 10 responses/choice, but NNCs were available on a progressive-ratio (PR) schedule wherein response cost (and unit price) increased following each NNC choice (10,160,320…8400 responses/choice). Results were analyzed using ANOVAs and a binomial test (p\u3c.05). Results: Participants preferred NNCs over VLNCs in Condition 1, but shifted preference to VLNCs in Condition 2 (p\u3c.001) immediately before the point in the PR progression where unit price for NNCs exceeded unit price for VLNCs (p\u3c.001). Additionally, this preference shift corresponded with reduced total cigarette consumption compared to Condition 1 levels (p\u3c.001). Conclusions: These results suggest that unit price of nicotine underpins cigarette preference and may provide a metric by which regulators can predict product preference and potentially impact it through policy. These results also demonstrate that VLNCs sustain lower smoking rates than NNCs even under acute laboratory conditions

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell

Effects of Chronic Electronic Vapor Exposure on Body Weight, Appetite, and Metabolism

Cigarette smokers weigh less than non-smokers and gain weight upon smoking cessation. Electronic cigarettes (E-cigs) have been used as a smoking cessation tool among many, however, their effects on metabolism, appetite, and energy balance are virtually unknown. This study compares the effects of chronic E-cig vapor exposure on body mass, food intake, metabolism, and body composition in mice. We hypothesized that E-cig exposure would elicit similar changes on body mass, body composition, food intake, and metabolic and appetite-regulating markers as conventional cigarettes (i.e. 3R4F reference cigarette). Female C57BL/6 mice were exposed to filtered room air (n=15), mainstream smoke from 3R4F reference cigarettes (n=15), or E-cig vapor (n=15) for a total of 8-months (4 h/d, 5d/wk). Body mass, food intake, metabolic and appetite-regulating markers, heat production, and body composition were measured. Weight gain, fat-free mass (FFM), and fat mass were significantly elevated in E-cig and control mice compared to 3R4F mice. Food consumption and heat production (kcal expended/hr) was significantly increased in E-cig mice compared to control and 3R4F mice. Appetite-regulating markers (NPY, POMC, leptin, and GLP-1) were similar between all groups. Mitochondrial uncouplers (UCP-1 and UCP-3) remained unchanged between E-cig and control groups, however, UCP-1 was significantly elevated in E-cig mice compared to 3R4F mice and UCP-3 was significantly elevated in control vs. 3R4F mice. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were also significantly elevated in E-cig and 3R4F mice compared to control mice, while respiratory exchange ratios (RER) were unchanged. Unlike conventional cigarettes, we found that E-cig exposure did not elicit reductions in total body or adipose mass. This suggests the effects of E-cig may not be the same as that occurring with traditional tobacco cigarettes, or that the exposure to nicotine and/or other chemicals in the E-cig liquid elicits a different response on appetite or feeding behavior. While E-cig mice increased food intake, their basal metabolism was also elevated, suggesting energy dissipation resulting in a similar net energy balance compared to control mice. Further studies are needed to evaluate the effect that flavorings and/or the compounds produced in E-cig vapor exert on metabolism, energy balance, and the neural regulation of appetite

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function

Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed

Formulating a Regulatory Stance: The Comparative Politics of E-Cigarette Regulation in Australia, Canada and New Zealand

Depending on who is asked, electronic cigarettes (e-cigarettes) are either the worst thing to happen to the fight against tobacco or a godsent technology that will dramatically improve public health. Unlike tobacco cigarettes, where the world has converged on common regulatory policies intent on shrinking the market for those deadly products, jurisdictions diverge immensely in their regulatory goals towards e-cigarettes. Illustratively, in March 2017, the government of New Zealand announced it would legalize the sale of e-cigarettes. In February 2017, Australia’s pharmaceutical regulator rejected a proposal to legalize the sale of nicotine for use in e-cigarettes because evidence of the product’s long-term safety was lacking. Previously, the medicines regulator in each country agreed the sale of e-cigarettes with nicotine should not be legal. Within a month, two wealthy, democratic, neighboring former British colonies, with a history of being leaders in tobacco control policy, led by right-wing governments, parted company on this momentous policy issue. Why? Through a comparative study of Australia, Canada, and New Zealand, this study addresses how the concerns of public health advocates, business, bureaucrats, and politicians around e-cigarettes are translated into regulatory policy. Political science has only begun to apply its theories to the study of public health policies, and most of what drives public health policy outcomes remains poorly understood. Here, a qualitative comparative approach of three most-similar country cases is used to determine what factors enabled e-cigarette regulatory policy change or stasis. To imbue meaning to the purpose of a regulatory framework, the study introduces an organizing framework called a regulatory stance, which describes the intent of a regulatory framework to alter the size of a market in the future relative to the present. All three case countries began with a prohibitionist regulatory stance towards e-cigarettes, which intended the market for e-cigarettes should make up none of their economies. New Zealand and Canada soon adopted expansionist regulatory stances, meaning that these countries intended on growing the size of their e-cigarette markets. Australia kept its original regulatory stance. Structured by John W. Kingdon’s Multiple Streams Approach to agenda-setting, the case studies examine how and why a country’s regulatory stance towards e-cigarettes, changed or did not. I employed qualitative techniques of document collection and key informant interviews to piece together a comparative study of e-cigarette regulatory policy and politics. In the Multiple Streams Approach, the problem and policy streams must become primed before they can merge with the politics stream and open a policy window. The problem stream became primed once the current regulatory policy was deemed a failure when it was rejected by the courts as illegal, rejected by bureaucracies as not worth enforcing, or it failed to advance the fight against smoking. Next, the policy stream became primed once the public health policy community agreed on a consensus alternative regulatory stance expanding the market for e-cigarettes. Finally, the politics stream was primed when conditions in the problem and policy stream granted left-wing politicians’ permission to support a regulatory stance change favored by business groups. This freed right-wing politicians to support regulatory stance change without facing a political penalty. Once all stakeholders agreed they would benefit more by adopting the alternative regulatory stance than by continuing with the failed policy, a policy window to change the failed e-cigarette regulatory stance opened.PHDHealth Services Organization & PolicyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162993/1/acliber_1.pd

Nicotine' actions on energy balance: friend or foe?

Teixit adipós; Receptors nicotínics; ObesitatTejido adiposo; Receptores nicotínicos; ObesidadAdipose tissue; Nicotinic receptors; ObesityObesity has reached pandemic proportions and is associated with severe comorbidities, such as type 2 diabetes mellitus, hepatic and cardiovascular diseases, and certain cancer types. However, the therapeutic options to treat obesity are limited. Extensive epidemiological studies have shown a strong relationship between smoking and body weight, with non-smokers weighing more than smokers at any age. Increased body weight after smoking cessation is a major factor that interferes with their attempts to quit smoking. Numerous controlled studies in both humans and rodents have reported that nicotine, the main bioactive component of tobacco, exerts a marked anorectic action. Furthermore, nicotine is also known to modulate energy expenditure, by regulating the thermogenic activity of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT), as well as glucose homeostasis. Many of these actions occur at central level, by controlling the activity of hypothalamic neuropeptide systems such as proopiomelanocortin (POMC), or energy sensors such as AMP-activated protein kinase (AMPK). However, direct impact of nicotine on metabolic tissues, such as BAT, WAT, liver and pancreas has also been described. Here, we review the actions of nicotine on energy balance. The relevance of this interaction is interesting, because considering the restricted efficiency of obesity treatments, a possible complementary approach may focus on compounds with known pharmacokinetic profile and pharmacological actions, such as nicotine or nicotinic acetylcholine receptors signaling.Xunta de Galicia (RN: 2016-PG057; ML: 2016-PG068); Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of EU (RN: RTI2018-099413-B-I00; CD: BFU2017- 87721-P; ML: RTI2018-101840-B-I00; JMF-R and ML: BFU2017- 90578-REDT/Adipoplast); Instituto de Salud Carlos III (JMF-R: PI15–01934); Atresmedia Corporación (RN and ML); Fundación BBVA (RN); “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160022 (ML); European Foundation for the Study of Diabetes (RN); ERC Synergy Grant-2019-WATCH- 810331 (RN); US Na- tional Institutes of Health (KR: HL084207); the US Department of Vet- erans Affairs (KR: I01BX004249); The University of Iowa Fraternal Order of Eagles Diabetes Research Center (KR). PS-C is recipient of a fel- lowship from Xunta de Galicia (ED481B 2018/050). The CiMUS is sup- ported by the Xunta de Galicia (2016-2019, ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII