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Research Report Series (2016): Tobacco/Nicotine PDF

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What are the medical consequences of tobacco use? See page 4. from the director: Tobacco use kills approximately 440,000 Americans each year, with one in every five U.S. deaths the result of smoking. Smoking harms nearly every organ in the body, causes many diseases, and compromises Tobacco/ smokers’ health in general. Nicotine, a component of tobacco, is the primary reason that tobacco is addictive, although cigarette smoke contains many other dangerous chemicals, Nicotine including tar, carbon monoxide, acetaldehyde, nitrosamines, and more. An improved overall understanding of addiction and of nicotine as an addictive drug has been instrumental in developing medications and behavioral treatments for tobacco addiction. For example, the nicotine patch and gum, now readily available at drugstores and supermarkets nationwide, have proven effective for smoking cessation when combined with behavioral therapy. Advanced neuroimaging technologies make it possible for researchers to observe changes in brain function that result from smoking tobacco. What Are the Extent and Researchers are now also identifying genes that predispose people to Impact of Tobacco Use? tobacco addiction and predict their response to smoking cessation treatments. These findings— According to the 2010 National Survey on Drug Use and many other recent research accomplishments—present unique and Health, an estimated 69.6 million Americans aged opportunities to discover, develop, 12 or older reported current use of tobacco — 58.3 and disseminate new treatments for tobacco addiction, as well as million (23.0 percent of the population) were current cigarette scientifically based prevention smokers, 13.2 million (5.2 percent) smoked cigars, 8.9 million programs to help curtail the public (3.5 percent) used smokeless tobacco, and 2.2 million (0.8 health burden that tobacco use represents. percent) smoked pipes, confirming that tobacco is one of the We hope this Research Report will most widely abused substances in the United States. Although help readers understand the harmful the numbers of people who smoke are still unacceptably high, effects of tobacco use and identify best practices for the prevention and according to the Centers for Disease Control and Prevention treatment of tobacco addiction. there has been a decline of almost 50 percent since 1965. Nora D. Volkow, M.D. Director continued inside National Institute on Drug Abuse Tobacco/ Research Report Series Nicotine NIDA’s 2011 Monitoring the disorder, major depression, and and medical care costs associated Future survey of 8th-, 10th-, and other mental illnesses is twofold to with disease caused by secondhand 12th-graders, which is used to track fourfold higher than in the general smoke. In addition to healthcare drug use patterns and attitudes, has population; and among people with costs, the costs of lost productivity also shown a striking decrease in schizophrenia, smoking rates as high due to smoking effects are estimated smoking trends among the Nation’s as 90 percent have been reported. at $97 billion per year, bringing youth. The latest results indicate Tobacco use is the leading a conservative estimate of the that about 6 percent of 8th-graders, preventable cause of death in the economic burden of smoking to 12 percent of 10th-graders, and United States. The impact of tobacco more than $193 billion per year. 19 percent of 12th-graders had use in terms of morbidity and used cigarettes in the 30 days prior mortality to society is staggering. to the survey—the lowest levels Economically, more than $96 How Does in the history of the survey. billion of total U.S. healthcare costs Tobacco Deliver The declining prevalence of each year are attributable directly Its Effects? cigarette smoking among the general to smoking. However, this is well U.S. population, however, is not below the total cost to society There are more than 7,000 reflected in patients with mental because it does not include burn chemicals found in the smoke illnesses. The rate of smoking care from smoking-related fires, of tobacco products. Of these, in patients suffering from post- perinatal care for low-birthweight nicotine, first identified in the traumatic stress disorder, bipolar infants of mothers who smoke, early 1800s, is the primary reinforcing component of tobacco. Cigarette smoking is the most popular method of using tobacco; however, many people also use smokeless tobacco products, such Trends in Prevalence of Cigarette Use as snuff and chewing tobacco. These smokeless products for 8th-, 10th-, and 12th-Graders also contain nicotine, as well as many toxic chemicals. Percentage of Students Using Cigarettes Over a 30-Day Period, 1995–2011 The cigarette is a very efficient 40 and highly engineered drug delivery system. By inhaling tobacco smoke, 35 the average smoker takes in 1–2 12th grade milligrams of nicotine per cigarette. 30 e When tobacco is smoked, nicotine s U g 25 rapidly reaches peak levels in the ortin 10th grade bloodstream and enters the brain. Rep 20 A typical smoker will take 10 puffs nt on a cigarette over a period of 5 e erc 15 8th grade minutes that the cigarette is lit. P Thus, a person who smokes about 10 1½ packs (30 cigarettes) daily gets 300 “hits” of nicotine to the brain 5 each day. In those who typically 1995 96 97 98 99 2000 01 02 03 04 05 06 07 08 09 10 11 Source: University of Michigan, 2011 Monitoring the Future Survey. 2 NIDA Research Report Series do not inhale the smoke—such other drugs of abuse and is thought as cigar and pipe smokers and to underlie the pleasurable sensations smokeless tobacco users—nicotine experienced by many smokers. is absorbed through the mucosal For many tobacco users, long-term membranes and reaches peak blood brain changes induced by continued levels and the brain more slowly. nicotine exposure result in addiction. Immediately after exposure to Nicotine’s pharmacokinetic nicotine, there is a “kick” caused properties also enhance its abuse in part by the drug’s stimulation potential. Cigarette smoking of the adrenal glands and produces a rapid distribution of resulting discharge of epinephrine nicotine to the brain, with drug (adrenaline). The rush of adrenaline levels peaking within 10 seconds stimulates the body and causes of inhalation. However, the acute an increase in blood pressure, effects of nicotine dissipate respiration, and heart rate. quickly, as do the associated feelings of reward, which causes the smoker to continue dosing to Is Nicotine maintain the drug’s pleasurable Addictive? effects and prevent withdrawal. Nicotine withdrawal symptoms Yes. Most smokers use tobacco include irritability, craving, regularly because they are depression, anxiety, cognitive and addicted to nicotine. Addiction is attention deficits, sleep disturbances, Tobacco plants characterized by compulsive drug- and increased appetite. These seeking and abuse, even in the face symptoms may begin within a few of negative health consequences. It is hours after the last cigarette, quickly well-documented that most smokers driving people back to tobacco Most smokers identify tobacco use as harmful use. Symptoms peak within the and express a desire to reduce or identify tobacco first few days of smoking cessation stop using it, and nearly 35 million and usually subside within a few use as harmful and of them want to quit each year. weeks. For some people, however, express a desire Unfortunately, more than 85 percent symptoms may persist for months. of those who try to quit on their to reduce or stop Although withdrawal is related own relapse, most within a week. to the pharmacological effects using it, and nearly Research has shown how of nicotine, many behavioral 35 million want to nicotine acts on the brain to produce factors can also affect the severity quit each year. a number of effects. Of primary of withdrawal symptoms. For importance to its addictive nature some people, the feel, smell, and are findings that nicotine activates sight of a cigarette and the ritual reward pathways—the brain circuitry of obtaining, handling, lighting, that regulates feelings of pleasure. and smoking the cigarette are all A key brain chemical involved in associated with the pleasurable cravings often persist. Behavioral mediating the desire to consume effects of smoking and can make therapies can help smokers drugs is the neurotransmitter withdrawal or craving worse. identify environmental triggers dopamine, and research has shown Nicotine replacement therapies such of craving so they can employ that nicotine increases levels of as gum, patches, and inhalers may strategies to prevent or circumvent dopamine in the reward circuits. This help alleviate the pharmacological these symptoms and urges. reaction is similar to that seen with aspects of withdrawal; however, 3 NIDA Research Report Series adolescent animals display far overall rates of death from cancer more sensitivity to this reinforcing are twice as high among smokers as Nicotine replacement effect, which suggests that the nonsmokers, with heavy smokers therapies such as gum, brains of adolescents may be more having rates that are four times patches, and inhalers vulnerable to tobacco addiction. greater than those of nonsmokers. may help alleviate Foremost among the cancers caused by tobacco use is lung cancer— the pharmacological cigarette smoking has been linked to aspects of withdrawal. What Are about 90 percent of all cases of lung the Medical cancer, the number one cancer killer Consequences of both men and women. Smoking of Tobacco Use? is also associated with cancers of the Are There Other mouth, pharynx, larynx, esophagus, Chemicals That Cigarette smoking kills an estimated stomach, pancreas, cervix, kidney, 440,000 U.S. citizens each year— May Contribute bladder, and acute myeloid leukemia. more than alcohol, illegal drug use, to Tobacco In addition to cancer, smoking homicide, suicide, car accidents, causes lung diseases such as chronic Addiction? and AIDS combined. Between 1964 bronchitis and emphysema, and and 2004, more than 12 million Yes, research is showing that it has been found to exacerbate Americans died prematurely from nicotine may not be the only asthma symptoms in adults and smoking, and another 25 million U.S. ingredient in tobacco that affects its children. About 90 percent of all smokers alive today will most likely addictive potential. Using advanced deaths from chronic obstructive die of a smoking-related illness. neuroimaging technology, scientists pulmonary diseases are attributable Cigarette smoking harms nearly can see the dramatic effect of to cigarette smoking. It has also every organ in the body. It has been cigarette smoking on the brain and been well-documented that smoking conclusively linked to cataracts and are finding a marked decrease in substantially increases the risk of pneumonia, and accounts for about the levels of monoamine oxidase heart disease, including stroke, one-third of all cancer deaths. The (MAO), an important enzyme that is responsible for the breakdown of dopamine. This change is likely caused by some ingredient in tobacco smoke other than nicotine, because we know that nicotine itself does not dramatically alter MAO levels. The decrease in two forms of MAO (A and B) results in higher dopamine levels and may be another reason that smokers continue to smoke—to sustain the high dopamine levels that lead to the desire for repeated drug use. Animal studies by NIDA- funded researchers have shown that acetaldehyde, another chemical found in tobacco smoke, dramatically increases the reinforcing properties of nicotine Using advanced neuroimaging technology, scientists can see the dramatic effect of and may also contribute to tobacco cigarette smoking on the brain and body and are finding a marked decrease in the addiction. The investigators further levels of monoamine oxidase (MAO), an important enzyme that is responsible for report that this effect is age-related: the breakdown of dopamine. (Source: Fowler et al., 2003) 4 NIDA Research Report Series Are There Safe Tobacco Products? The adverse health effects of tobacco use are well known, yet many people do not want to quit or have difficulty quitting. As a result, there has been a recent surge in the development of tobacco products that claim to reduce exposure to harmful tobacco constituents or to have fewer health risks than conventional products. These “potentially reduced exposure products” (PREPs), which include cigarettes and smokeless tobacco (e.g., snuff, tobacco lozenges), have Sticky, brown tar coats the not yet been evaluated sufficiently to lungs of tobacco smokers. determine whether they are indeed Along with thousands of associated with reduced risk of other damaging chemicals, tar can lead to lung cancer disease. Recent studies indicate that and acute respiratory the levels of carcinogens in these diseases. PREPs range from relatively low to comparable to conventional tobacco products. These studies conclude that medicinal nicotine (found in the heart attack, vascular disease, and pets. Death usually results in and aneurysm. Smoking causes a few minutes from respiratory nicotine patch and gum) is a safer coronary heart disease, the leading failure caused by paralysis. alternative than these modified cause of death in the United States: Although we often think of tobacco products. cigarette smokers are 2–4 times medical consequences that result more likely to develop coronary from direct use of tobacco products, heart disease than nonsmokers. passive or secondary smoke also Learn About Exposure to high doses of increases the risk for many diseases. Electronic Cigarettes nicotine, such as those found in Environmental tobacco smoke some insecticide sprays, can be is a major source of indoor air extremely toxic as well, causing contaminants; secondhand smoke Read NIDA’s DrugFacts: vomiting, tremors, convulsions, is estimated to cause approximately Electronic Cigarettes (e-Cigarettes) at and death. In fact, one drop of pure 3,000 lung cancer deaths per year www.drugabuse.gov/publications/ nicotine can kill a person. Nicotine among nonsmokers and contributes drugfacts/electronic-cigarettes- poisoning has been reported to more than 35,000 deaths related e-cigarettes for information about from accidental ingestion of to cardiovascular disease. Exposure electronic cigarettes, including how insecticides by adults and ingestion to tobacco smoke in the home is of tobacco products by children also a risk factor for new cases safe they are compared to tobacco cigarettes. 5 NIDA Research Report Series Tobacco Use and Comorbidity There is clear evidence of high rates of psychiat- their nicotine dependence diagnosed or properly ric comorbidity, including other substance abuse, treated. Preventing the early onset of smoking and among adolescents and adults who smoke. For treating its young victims are critical primary-care pri- example, it has been estimated that individuals with orities, the fulfillment of which could have a dramatic psychiatric disorders purchase approximately 44 impact on our ability to prevent or better address a percent of all cigarettes sold in the United States, wide range of mental disorders throughout life. which undoubtedly contributes to the disproportion- Among adults, the rate of major depressive epi- ate rates of morbidity and mortality in these popula- sodes is highest in nicotine-dependent individuals, tions. In addition, studies have shown that as many lower in nondependent current smokers, and lowest as 80 percent of alcoholics smoke regularly, and that in those who quit or never started smoking. Further- a majority of them will die of smoking-related, rather more, there is evidence showing that, for those who than alcohol-related, disease. have had more than one episode, smoking cessation In young smokers, the behavior appears to be may increase the likelihood of a new major depres- strongly associated with increased risk for a variety sive episode. Adult tobacco use also increases of mental disorders. In some cases—such as with risk for the later development of anxiety disorders, conduct disorders and attention-deficit hyperactivity which may be associated with an increased severity disorder—these disorders may precede the onset of of withdrawal symptoms during smoking cessation smoking, while in others—such as with substance therapy. But the most extensive comorbidity overlap abuse—the disorders may emerge later in life. is likely the one that exists between smoking and Whether daily smoking among boys and girls is the schizophrenia, since, in clinical samples, the rate of result or the cause of a manifest psychiatric condi- smoking in patients with schizophrenia has ranged tion, it is troubling that so very few adolescents have as high as 90 percent. and increased severity of childhood concentrates in fetal blood, asthma. Additionally, dropped amniotic fluid, and breast milk. cigarettes are the leading cause of Combined, these factors can have residential fire fatalities, leading to severe consequences for the fetuses more than 1,000 deaths each year. and infants of smoking mothers. Smoking during pregnancy caused an estimated 910 infant deaths Smoking and annually from 1997 through 2001, Pregnancy— and neonatal care costs related What Are to smoking are estimated to be more than $350 million per year. the Risks? The adverse effects of smoking In the United States, it is estimated during pregnancy can include fetal that about 16 percent of pregnant growth retardation and decreased women smoke during their birthweight. The decreased consistent with what has been pregnancies. Carbon monoxide birthweights seen in infants of reported in infants exposed to other and nicotine from tobacco smoke mothers who smoke reflect a drugs. In some cases, smoking may interfere with the oxygen dose-dependent relationship— during pregnancy may be associated supply to the fetus. Nicotine also the more the woman smokes with spontaneous abortions and readily crosses the placenta, and during pregnancy, the greater the sudden infant death syndrome concentrations in the fetus can reduction of infant birthweight. (SIDS), as well as learning and be as much as 15 percent higher These newborns also display signs behavioral problems and an than maternal levels. Nicotine of stress and drug withdrawal increased risk of obesity in children. 6 NIDA Research Report Series In addition, smoking more than one pack a day during pregnancy nearly doubles the risk that the affected child will become addicted to tobacco if that child starts smoking. Are There Gender Differences in Tobacco Smoking? Several avenues of research now indicate that men and women differ in their smoking behaviors. For instance, women smoke fewer cigarettes per day, tend to use cigarettes with lower nicotine content, and do not inhale as deeply as men. However, it is unclear whether this is due to differences in sensitivity to nicotine or other factors that affect women Smoking and Adolescence In 2010, about 2.6 million American adolescents (aged 12–17) reported using a tobacco product in the month prior to the survey. In that same year, it was found that nearly 60 percent of new smokers were under the age of 18 when they first smoked a cigarette. Of smokers under age 18, more than 6 million will likely die prematurely from a smoking-related disease. Tobacco use in teens is not only the result of psychosocial influences, such as peer pressure; recent research suggests that there may be biological reasons for this period of increased vulnerability. There is some evidence that intermittent smoking can result in the development of tobacco addiction in some teens. Animal models of teen smoking provide additional evidence of an increased vulnerability. Adolescent rats are more susceptible to the reinforcing effects of nicotine than adult rats, and take more nicotine when it is available than do adult animals. Large-scale smoking Adolescents may also be more sensitive to the reinforcing effects of cessation trials show nicotine in combination with other chemicals found in cigarettes, thus increasing susceptibility to tobacco addiction. As mentioned earlier, that women are acetaldehyde increases nicotine’s addictive properties in adolescent, less likely to initiate but not adult, animals. A recent study also suggests that specific genes quitting and may be may increase risk for addiction among people who begin smoking during adolescence. NIDA continues to actively support research aimed more likely to relapse at increasing our understanding of why and how adolescents become if they do quit. addicted, and to develop prevention and treatment strategies to meet their specific needs. 7 NIDA Research Report Series are that withdrawal may be more intense for women or that women are more concerned about weight gain. Although postcessation weight gain is typically modest (about 5–10 pounds), concerns about this may be an obstacle to treatment success. In fact, NIDA research has found that when women’s weight concerns were addressed during cognitive-behavioral therapy, other cancers, and coronary heart they were more successful at disease. A 35-year-old man who quits quitting than women who were in a smoking will, on average, increase Smoking cessation can program designed only to attenuate his life expectancy by 5 years. have immediate health postcessation weight gain. Other NIDA researchers have found that Nicotine Replacement benefits. For example, medications used for smoking Treatments within 24 hours of cessation, such as bupropion and Nicotine replacement therapies quitting, blood pressure naltrexone, can also attenuate (NRTs), such as nicotine gum and and chances of heart postcessation weight gain and could the transdermal nicotine patch, were become an additional strategy for the first pharmacological treatments attack decrease. enhancing treatment success. approved by the Food and Drug It is important for treatment Administration (FDA) for use in professionals to be aware that smoking cessation therapy. NRTs are standard regimens may have to be used (in conjunction with behavioral differently, such as social factors or adjusted to compensate for gender support) to relieve withdrawal the sensory aspects of smoking. differences in nicotine sensitivity symptoms—they produce less The number of smokers in the and in other related factors that severe physiological alterations than United States declined in the 1970s contribute to continued smoking. tobacco-based systems and generally and 1980s, remained relatively stable provide users with lower overall throughout the 1990s, and declined nicotine levels than they receive further through the early 2000s. Are There with tobacco. An added benefit is Because this decline in smoking was Effective that these forms of nicotine have greater among men than women, Treatments little abuse potential since they do the prevalence of smoking is only for Tobacco not produce the pleasurable effects slightly higher for men today than it Addiction? of tobacco products, nor do they is for women. Several factors appear contain the carcinogens and gases to be contributing to this narrowing Yes, extensive research has associated with tobacco smoke. gender gap, including women shown that treatments for tobacco Behavioral treatments, even beyond being less likely than men to quit. addiction do work. Although some what is recommended on packaging Large-scale smoking cessation smokers can quit without help, labels, have been shown to enhance trials show that women are less many individuals need assistance the effectiveness of NRTs and likely to initiate quitting and may with quitting. This is particularly improve long-term outcomes. be more likely to relapse if they do important because smoking cessation The FDA’s approval of nicotine quit. In cessation programs using can have immediate health benefits. gum in 1984 marked the availability nicotine replacement methods, such For example, within 24 hours of (by prescription) of the first NRT as the patch or gum, the nicotine quitting, blood pressure and chances on the U.S. market. In 1996, the does not seem to reduce craving as of heart attack decrease. Long-term FDA approved Nicorette gum for effectively for women as for men. benefits of smoking cessation include over-the-counter (OTC) sales. Other factors that may contribute decreased risk of stroke, lung and Whereas nicotine gum provides to women’s difficulty with quitting 8 NIDA Research Report Series some smokers with the desired control over dose and the ability to relieve cravings, others are unable to tolerate the taste and chewing Twin studies indicate demands. In 1991 and 1992, the FDA that approximately approved four transdermal nicotine patches, two of which became OTC 40–70 percent of products in 1996. In 1996 a nicotine a person’s risk of nasal spray, and in 1998 a nicotine becoming addicted inhaler, also became available to nicotine depends by prescription, thus meeting the on his or her genes. needs of many additional tobacco users. All the NRT products— gum, patch, spray, and inhaler— appear to be equally effective. other antidepressants and an settings. Over the past decade, antihypertensive medication. however, researchers have been Scientists are also investigating adapting these approaches for mail, the potential of a vaccine that telephone, and Internet formats, targets nicotine for use in relapse which can be more acceptable prevention. The nicotine vaccine is and accessible to smokers who designed to stimulate the production are trying to quit. In 2004, the of antibodies that would block access U.S. Department of Health and of nicotine to the brain and prevent Human Services (HHS) established nicotine’s reinforcing effects. a national toll-free number, 800-QUIT-NOW (800-784-8669), Behavioral Treatments Additional Medications Behavioral interventions play an Although the primary focus of integral role in smoking cessation pharmacological treatments for treatment, either in conjunction tobacco addiction has been nicotine with medication or alone. A variety replacement, other treatments are of methods can assist smokers also available. For example, the with quitting, ranging from self- antidepressant bupropion was help materials to individual approved by the FDA in 1997 to cognitive-behavioral therapy. These help people quit smoking and is interventions teach individuals marketed as Zyban. Varenicline to recognize high-risk smoking tartrate (Chantix) is a medication that situations, develop alternative coping recently received FDA approval for smoking cessation. This medication, strategies, manage stress, improve to serve as a single access point for which acts at the sites in the brain problemsolving skills, and increase smokers seeking information and affected by nicotine, may help social support. Research has also assistance in quitting. Callers to the people quit by easing withdrawal shown that the more therapy is number are routed to their State’s symptoms and blocking the effects of tailored to a person’s situation, the smoking cessation quitline or, in nicotine if people resume smoking. greater the chances are for success. States that have not established Several other non-nicotine Traditionally, behavioral quitlines, to one maintained by medications are being approaches were developed and the National Cancer Institute. In investigated for the treatment delivered through formal settings, addition, a new HHS Web site of tobacco addiction, including such as smoking cessation clinics (www.smokefree.gov) offers and community and public health 9 NIDA Research Report Series online advice and downloadable 40–70 percent of a person’s risk peripheral arterial disease. NIDA information to make cessation easier. of becoming addicted to nicotine is currently supporting large-scale Quitting smoking can be difficult. depends on his or her genes. genome-wide association studies People can be helped during the Although complex diseases like to uncover additional genetic time an intervention is delivered; addiction involve large numbers risk factors in order to better however, most intervention programs of genes interacting with a wide understand tobacco addiction and are short-term (1–3 months). variety of environmental factors, its adverse effects on health. Within 6 months, 75–80 percent the contribution of a particular In addition to predicting an of people who try to quit smoking gene can be substantial. individual’s risk for nicotine relapse. Research has now shown Genetic variants associated with addiction, genetic markers that extending treatment beyond nicotine metabolism, for example, can also help predict whether the typical duration of a smoking have been shown to influence how medications (like bupropion) will cessation program can produce quit people smoke. Slow metabolizers effectively help a smoker quit. rates as high as 50 percent at 1 year. smoke fewer cigarettes per day and This takes root in the emerging have a higher likelihood of quitting, field of pharmacogenomics, and there is greater abstinence which investigates how genes New Frontiers among individuals receiving influence a patient’s response to nicotine patch therapy. A recent drugs and medications. In the in Tobacco NIDA-funded study identified a future, genetic screening could Research variant in the gene for a nicotinic help clinicians select treatments, receptor subunit that doubled the adjust dosages, and avoid or If so many smokers want to risk for nicotine addiction among minimize adverse reactions, quit, why are few able to do so smokers. A subsequent study tailoring smoking cessation successfully? To address this found that this gene variant also therapies to an individual’s question, scientists are increasingly increased susceptibility to the unique genetic inheritance. focusing on the powerful role severe health consequences of of genetics in addiction. Twin smoking, including lung cancer and studies indicate that approximately Glossary Dopamine: A neurotransmitter Nicotine: An alkaloid derived present in regions of the brain from the tobacco plant that is Addiction: A chronic, relapsing that regulate movement, emotion, primarily responsible for smoking’s disease characterized by compulsive motivation, and feelings of pleasure. psychoactive and addictive effects. drug-seeking and abuse despite adverse consequences. It is Emphysema: A lung disease in Pharmacokinetics: The pattern of associated with long-lasting changes which tissue deterioration results in absorption, distribution, and excretion in the brain. increased air retention and reduced of a drug over time. exchange of gases. The result is Adrenal glands: Glands located difficulty breathing and shortness of Tobacco: A plant widely cultivated for above each kidney that secrete breath. its leaves, which are used primarily hormones, e.g., adrenaline. for smoking; the N. tabacum species Neurotransmitter: A chemical that is the major source of tobacco Carcinogen: Any substance that acts as a messenger to carry signals products. causes cancer. or information from one nerve cell to another. Withdrawal: A variety of symptoms Craving: A powerful, often that occur after chronic use of an uncontrollable desire for drugs. addictive drug is reduced or stopped. 10 NIDA Research Report Series

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