Nicotine Addiction for the Advancement Judith J

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Nicotine Addiction for the Advancement Judith J SCIENCE ADVANCES | REVIEW DISEASES AND DISORDERS Copyright © 2019 The Authors, some rights reserved; Current advances in research in treatment and recovery: exclusive licensee American Association Nicotine addiction for the Advancement Judith J. Prochaska1* and Neal L. Benowitz2 of Science. No claim to original U.S. Government Works. Distributed The health harms of combusted tobacco use are undeniable. With market and regulatory pressures to reduce the under a Creative harms of nicotine delivery by combustion, the tobacco product landscape has diversified to include smokeless, Commons Attribution heated, and electronic nicotine vaping products. Products of tobacco combustion are the main cause of smoking- NonCommercial induced disease, and nicotine addiction sustains tobacco use. An understanding of the biology and clinical features License 4.0 (CC BY-NC). of nicotine addiction and the conditioning of behavior that occurs via stimuli paired with frequent nicotine dosing, as with a smoked cigarette, is important for informing pharmacologic and behavioral treatment targets. We review current advances in research on nicotine addiction treatment and recovery, with a focus on conventional combustible cigarette use. Our review covers evidence-based methods to treat smoking in adults and policy approaches to prevent nicotine product initiation in youth. In closing, we discuss emerging areas of evidence and consider new directions for advancing the field. INTRODUCTION heat nicotine to an inhalable aerosol from a plug of tobacco (i.e., “To lower nicotine too much might end up destroying the nicotine heated or heat-not-burn tobacco) or from an e-liquid (nicotine habit in a large number of consumers and prevent it from ever being vaping device; e.g., e-cigarette, vape pen, and pod), and in pharmaceutical- acquired by new smokers.” grade nicotine replacement therapies (NRTs) (i.e., gum, lozenge, – British American Tobacco Company internal document, patch, nasal spray, mouth spray, and inhaler). Cigars come in a variety June 1959 (1). of sizes down to little filtered cigars, some discernible from cigarettes Combusted tobacco use remains a major cause of premature only by their tobacco leaf wrapper. Despite the diversification, disability and death around the world (2). Cigarette smoke contains conventional combusted cigarettes remain, by far, the most com- an estimated 7000 different chemical compounds, of which at least mon nicotine product used by adults in the United States and in 70 are proven or suspected human carcinogens including arsenic, most places globally. Worldwide, there are approximately 1 billion benzene, formaldehyde, lead, nitrosamines, and polonium 210. smokers (5). Tobacco smoke also contains poisonous gasses: carbon monoxide, While products of tobacco combustion are the main cause of hydrogen cyanide, butane, toluene, and ammonia. Little cigars and smoking-induced disease, nicotine addiction sustains tobacco use water pipes deliver similar toxicants. (8). Nicotine addiction, in the form of cigarette smoking, causes more Tobacco smoking causes about half a million U.S. deaths harm to public health than any other drug addiction. Reflected in annually, of which 50,000 are among nonsmokers exposed to the quote above, at least since the 1950s, the tobacco industry has secondhand smoke (3, 4). More than half of all long-term smokers researched and recognized, decades before it became generally die from a tobacco-caused disease, with an average loss of at least understood in the scientific community, that nicotine is an addictive 10 years of life (3). Smoking causes 87% of lung cancer deaths, 61% drug and central to their business (9). An understanding of the clinical of pulmonary disease deaths [chronic obstructive pulmonary disease features of nicotine addiction and the behavioral conditioning that (COPD) and emphysema], and one in three cancer deaths. In the occurs with frequent nicotine dosing is important for informing 50 years following the U.S. Surgeon General’s first report on tobacco pharmacologic and behavioral treatment targets. (1964–2014), 20 million Americans died from smoking, and an We review current advances in research on nicotine addiction estimated 1 billion people will die worldwide this century (3, 5). For treatment and recovery. The “Tobacco Product Use and Nicotine every person who dies from smoking, at least 30 people live with Addiction” section covers the changing landscape of nicotine products serious smoking-related illnesses costing >$300 billion annually, with with comparison of use patterns among adults and adolescents in nearly $170 billion in direct medical costs and $156 billion in lost the United States. The pharmacology of nicotine and effects on the worker productivity (3, 6). brain are then reviewed, with consideration of particularly vulnera- The health harms of combusted tobacco use are now undeniable ble populations. The “Treating Nicotine Addiction in Adults, with a (7). With market and regulatory pressures to reduce the harms of Focus on Conventional Cigarettes” section focuses on treatment of nicotine delivery by combustion, the tobacco product landscape has nicotine addiction with attention to counseling and behavioral diversified (Table 1). Nicotine now comes in smokeless tobacco approaches and cessation medications. The tobacco treatment litera- prepackaged pouches (i.e., snus tobacco), in electronic devices that ture is far more developed for combusted cigarettes and relatively sparse in other product areas. We focus on adults given develop- mental differences in adolescents’ preferred nicotine product type, 1Stanford Prevention Research Center, Department of Medicine, Stanford University, 2 use patterns, addiction profile, and treatment efficacy. The tobacco Stanford, CA, USA. Program in Clinical Pharmacology, Division of Cardiology, and treatment literature with adolescents largely consists of failed smoking the Center for Tobacco Control Research and Education, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. cessation trials (10), and while youth nicotine vaping is drawing *Corresponding author. Email: [email protected] public health concern and policy attention, no study, to date, has Prochaska and Benowitz, Sci. Adv. 2019; 5 : eaay9763 16 October 2019 1 of 23 SCIENCE ADVANCES | REVIEW Table 1. Diversity of tobacco products. Product Definition Types pH Nicotine levels Tobacco rolled in paper A typical cigarette weighs <1 g; Acidic, inhalable, pH 5.5–6 Average in rod, 13.5 mg for smoking regular length (70 mm long), (range: 11.9–14.5 mg); Cigarette king (84 mm), 100s (100 mm), nicotine yield to the and 120s (120 mm) smoker: 1–1.5 mg/cigarette Air-cured, fermented tobacco Small filtered cigars (0.9–1.3 g pH 6.5–8.0 inhalable and/or Nicotine content ranges wrapped in material made at tobacco), cigarillos (1.3–2.5 g tobacco), buccal depending on from 10 to 444 mg and Cigar least, in part, of tobacco leaf and large (premium) cigars product pH dependent on weight of the cigar Cannabis filled in a No pH data available Nicotine intake much lower hollowed-out cigarillo shell than from cigarette or cigar smoking, but, based on Blunt animal studies, could enhance rewarding effects of delta 9-tetrahydrocannbinaol Tobacco inserted between lip Snuff (ground tobacco), snus Products range from more Nicotine concentrations vary, and gum or snorted into (ground tobacco in a tea bag–like acidic, pH 5.2–7.1, to more range of 0.2 to 34 mg/g, the nose rather than pouch), chew (shredded alkaline for greater buccal the more alkaline Smokeless tobacco smoked by the user tobacco) absorption, pH 7.6–8.6 products are capable of delivering higher levels of nicotine Charcoal-heated flavored Water tobacco is a mixture of pH 3.8–5.8 Average of 1.13 mg/g and tobacco passed through a dried fruit, molasses and high of 3.30 mg/g for Waterpipe/Hookah water-filled chamber that glycerin, and conventional product containing cools the smoke tobacco leaf nicotine; nicotine-free for herbal (nontobacco) varieties Electronic devices that heat IQOS, Glo, and Ploom Tech pH 5.5–6 Nicotine delivery can match reconstituted tobacco that of conventional cigarettes Heated tobacco sticks treated with a glycerin humectant to deliver an aerosol Electric devices that produce Cigalikes/e-pens, tank systems, Free base e-liquid: alkaline, E-liquid nicotine content an aerosol from a liquid pods/nicotine salts (e.g., pH 7–9; nicotine salts: from 0 to 100 mg/ml. that typically contains benzoate and lactate) acidic, inhalable, pH Nicotine delivery can nicotine, propylene glycol, 3.5–6.8 match that of E-cigarette vegetable glycerin, and conventional cigarette but flavorings varies by device design (heating temperature), e-liquid nicotine content, and user behavior evaluated an intervention to treat e-cigarette use in adolescents. 1% (2.6 million) pipes, water pipes, or hookah (11). Among cigarette The “Tobacco Control Population-Based and Policy Approaches” smokers, 76% smoked daily (12). section gives greater attention to use in youth with review of In contrast, among U.S. adolescents, e-cigarettes exceed conven- the evidence for tobacco control policy interventions. The “Discus- tional cigarette use. In 2018, past 30-day e-cigarette use was reported sion: What Evidence Is Needed” section closes with discussion of by 21% of high school (3.05 million) and 5% of middle school emerging areas and consideration of new directions for advancing (570,000) students, and combustible cigarette use
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