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What are the medical consequences of tobacco use? See page 4.

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Tobacco use kills approximately 440,000 Americans each year, with one in every five U.S. the result of . Smoking harms nearly every organ in the body, causes many diseases, and compromises smokers’ health in general. , a component of tobacco, is the primary reason that tobacco is addictive, although smoke contains Tobacco/ many other dangerous chemicals, including , , acetaldehyde, nitrosamines, and more. An improved overall understanding Nicotine of and of nicotine as an addictive has been instrumental in developing medications and behavioral treatments for tobacco addiction. For example, the and gum, now readily available at drugstores and supermarkets nationwide, have proven effective for when combined with behavioral therapy.

Advanced neuroimaging technologies make it possible for researchers to observe changes in brain function that result from smoking tobacco. Researchers are now also identifying What Are the Extent and genes that predispose people to Impact of Tobacco Use? tobacco addiction and predict their response to smoking cessation treatments. These findings— ccording 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 A 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 , 8.9 million programs to help curtail the public health burden that tobacco use (3.5 percent) used , and 2.2 million (0.8 represents. percent) smoked pipes, confirming that tobacco is one of the We this Research Report will most widely abused substances in the . Although help readers understand the harmful effects of tobacco use and identify the numbers of people who smoke are still unacceptably high, 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 , 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 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 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 and . These smokeless products for 8th-, 10th-, and 12th-Graders also contain nicotine, as well Percentage of Students Using Cigarettes Over a 30-Day Period, 1995–2011 as many toxic chemicals. 40 The cigarette is a very efficient and highly engineered drug delivery

35 system. By inhaling , 12th grade the average smoker takes in 1–2 30 milligrams of nicotine per cigarette. When tobacco is smoked, nicotine 25 rapidly reaches peak levels in the 10th grade bloodstream and enters the brain. 20 A typical smoker will take 10 puffs on a cigarette over a period of 5 15 8th grade minutes that the cigarette is lit. Percent Reporting Use Reporting Percent 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

999897961995 2000 01 0605040302 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 of abuse and is thought as 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 (). 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 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. symptoms Yes. Most smokers use tobacco include irritability, , regularly because they are depression, , cognitive and addicted to nicotine. Addiction is attention deficits, disturbances, Tobacco 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 first few days of smoking cessation identify tobacco 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 Although withdrawal is related to reduce or stop 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 a number of effects. Of primary of withdrawal symptoms. For quit each year. 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 withdrawal or craving worse. identify environmental triggers , 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,

NIDA Research Report Series 3 adolescent animals display far overall rates of death from 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 caused the pharmacological by tobacco use is cancer— 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— bladder, and acute myeloid . May Contribute more than , 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 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 heart disease, including , 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 of tobacco smokers. determine whether they are indeed Along with thousands of associated with reduced risk of other damaging chemicals, tar can lead to disease. Recent studies indicate that and acute respiratory the levels of in these diseases. PREPs range from relatively low to comparable to conventional tobacco products. These studies conclude heart attack, vascular disease, and pets. Death usually results in that medicinal nicotine (found in the 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. nicotine, such as those found in Environmental tobacco smoke Electronic Cigarettes some 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 by adults and ingestion to tobacco smoke in the home is electronic cigarettes, including how of tobacco products by children also a risk factor for new cases safe they are compared to tobacco cigarettes.

NIDA Research Report Series 5

Tobacco Use and Comorbidity There is clear evidence of high rates of psychiat- their diagnosed or properly ric comorbidity, including other , 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 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 . 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 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 ? 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 nicotine in combination with other chemicals found in cigarettes, thus cessation trials show 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 may increase risk for addiction among people who begin smoking quitting and may be 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.

NIDA Research Report Series 7 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 by 5 years. have immediate health postcessation weight gain. Other benefits. For example, NIDA researchers have found that Nicotine Replacement medications used for smoking Treatments within 24 hours of cessation, such as and Nicotine replacement therapies quitting, blood pressure naltrexone, can also attenuate (NRTs), such as and and chances of heart postcessation weight gain and could the transdermal nicotine patch, were attack decrease. become an additional strategy for the first pharmacological treatments enhancing treatment success. approved by the 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 differently, such as social factors or used (in conjunction with behavioral adjusted to compensate for gender the sensory aspects of smoking. support) to relieve withdrawal differences in nicotine sensitivity The number of smokers in the symptoms—they produce less and in other related factors that United States declined in the 1970s severe physiological alterations than contribute to continued smoking. and 1980s, remained relatively stable tobacco-based systems and generally throughout the 1990s, and declined provide users with lower overall nicotine levels than they receive further through the early 2000s. Are There Because this decline in smoking was with tobacco. An added benefit is greater among men than women, Effective that these forms of nicotine have the prevalence of smoking is only Treatments little abuse potential since they do slightly higher for men today than it for Tobacco not produce the pleasurable effects is for women. Several factors appear Addiction? of tobacco products, nor do they to be contributing to this narrowing contain the carcinogens and gases Yes, extensive research has gender gap, including women associated with tobacco smoke. shown that treatments for tobacco being less likely than men to quit. Behavioral treatments, even beyond addiction do work. Although some Large-scale smoking cessation what is recommended on packaging smokers can quit without help, trials show that women are less labels, have been shown to enhance many individuals need assistance likely to initiate quitting and may the effectiveness of NRTs and with quitting. This is particularly be more likely to relapse if they do improve long-term outcomes. important because smoking cessation quit. In cessation programs using The FDA’s approval of nicotine can have immediate health benefits. nicotine replacement methods, such gum in 1984 marked the availability For example, within 24 hours of as the patch or gum, the nicotine (by prescription) of the first NRT quitting, blood pressure and chances does not seem to reduce craving as on the U.S. market. In 1996, the of heart attack decrease. Long-term effectively for women as for men. FDA approved Nicorette gum for benefits of smoking cessation include Other factors that may contribute over-the-counter (OTC) sales. decreased risk of stroke, lung and to women’s difficulty with quitting Whereas nicotine gum provides

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 and chewing Twin studies indicate demands. In 1991 and 1992, the FDA approved four transdermal nicotine that approximately 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 needs of many additional tobacco on his or her genes. 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 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), Additional Medications Behavioral Treatments Although the primary focus of Behavioral interventions play an pharmacological treatments for integral role in smoking cessation tobacco addiction has been nicotine treatment, either in conjunction replacement, other treatments are with medication or alone. A variety also available. For example, the of methods can assist smokers antidepressant bupropion was with quitting, ranging from self- approved by the FDA in 1997 to help materials to individual help people quit smoking and is cognitive-behavioral therapy. These marketed as Zyban. interventions teach individuals tartrate (Chantix) is a medication that to recognize high-risk smoking recently received FDA approval for situations, develop alternative coping 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

NIDA Research Report Series 9 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 , 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, If so many smokers want to receptor subunit that doubled the adjust dosages, and avoid or quit, why are few able to do so risk for nicotine addiction among minimize adverse reactions, successfully? To address this smokers. A subsequent study tailoring smoking cessation question, scientists are increasingly found that this gene variant also therapies to an individual’s focusing on the powerful role increased susceptibility to the unique genetic inheritance. of in addiction. Twin severe health consequences of studies indicate that approximately smoking, including lung cancer and

Glossary Dopamine: A neurotransmitter Nicotine: An derived present in regions of the brain from the tobacco 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 , which are used primarily hormones, e.g., adrenaline. for smoking; the N. tabacum species Neurotransmitter: A chemical that is the major source of tobacco : 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 References

Adams, E.K.; Miller, V.P.; Ernst, C.; Henningfield, J.E., Nicotine Abuse and Mental Health Services Nishimura, B.K.; Melvin, C.; and medications for smoking Administration, 2011. Available Merritt, R. Neonatal health care cessation. New Engl J Med at http://oas.samhsa.gov/ costs related to smoking during 333:1196–1203, 1995. NSDUH/2k10NSDUH/2k10Results. pregnancy. Health Economics Johnston, L.D.; O’Malley, P.M.; htm 11:193–206, 2002. Bachman, J.G.; and Schulenberg, Thorgeirsson, T.E., et al. A variant Belluzzi, J.D.; Wang, R.; and Leslie, J.E., Monitoring the Future associated with nicotine F.M. Acetaldehyde enhances National Results on Adolescent dependence, lung cancer and acquisition of nicotine self- Drug Use: Overview of Key peripheral arterial disease. Nature administration in adolescent rats. Findings, 2011. NIH . 452(7187):638–642, 2008. Neuropsychopharmacol 30:705– No. 11-6418. Bethesda, MD: U.S. Department of Health and Human 712, 2005. National Institute on Drug Services. Reducing Tobacco Use: Benowitz, N.L., Pharmacology Abuse, 2011. Available at: www. A Report of the Surgeon General. of nicotine: Addiction and monitoringthefuture.org. Atlanta: Centers for Disease therapeutics. Ann Rev Pharmacol Kalman, D.; Morissette, S.B.; and Control and Prevention, National Toxicol 36:597–613, 1996. George, T.P., Comorbidity Center for Chronic Disease Buka, S.L.; Shenassa, E.D.; and of smoking in patients with Prevention and Health Promotion, Niaura, R., Elevated risk of psychiatric and substance use Office on Smoking and Health, tobacco dependence among disorders. Am J Addict 14(2):106– 2000. Available at: http://www.cdc. offspring of mothers who 123, 2005. gov/tobacco/data_statistics/sgr/ smoked during pregnancy: A Levin, E.D.; Rezvani, A.H.; Montoya, index.htm. 30-year prospective study. Am J D.; Rose, J.E.; and Swartzwelder, U.S. Department of Health and Human Psychiatry 160:1978–1984, 2003. H.S., Adolescent-onset nicotine Services. The Health Benefits of Ernst, M.; Moolchan, E.T.; and self-administration modeled in Smoking Cessation: A Report of the Robinson, M.L., Behavioral and female rats. Psychopharmacol Surgeon General. Atlanta: Centers neural consequences of prenatal 169:141–149, 2003. for Disease Control and Prevention, exposure to nicotine. J Am Acad Perkins, K.A.; Donny, E.; and National Center for Chronic Disease Child Adolesc Psychiatry 40:630– Caggiula, A.R., Sex differences Prevention and Health Promotion, 641, 2001. in nicotine effects and self- Office on Smoking and Health, Fowler, J.S.; Volkow, N.D.; Wang, administration: Review of human 1990. Available at: http://www.cdc. G.J.; Pappas, N.; Logan, J.; and animal evidence. Nic and gov/tobacco/data_statistics/sgr/ MacGregor, R.; Alexoff, D.; Tobacco Res 1:301–315, 1999. index.htm. Shea, C.; Schlyer, D.; Wolf, Saccone, S.F., et al. U.S. Department of Health and A.P.; Warner, D.; Zezulkova, nicotinic receptor genes Human Services. The Health I.; and Cilento, R., Inhibition implicated in a nicotine Consequences of Smoking: A of monoamine oxidase B in dependence association study Report of the Surgeon General. the brains of smokers. Nature targeting 348 candidate genes Atlanta: Centers for Disease 22:733–736, 1996. with 3713 SNPs. Hum Mol Genet Control and Prevention, National Hatsukami, D.K.; Lemmonds, C.; 16(1):36–49, 2007. Center for Chronic Disease Zhang, Y.; Murphy, S.E.; Le, Substance Abuse and Mental Prevention and Health Promotion, C.; Carmella, S.G.; and Hecht, Health Services Administration, Office on Smoking and Health, S.S., Evaluation of carcinogen Results from the 2010 National 2004. Available at: http://www.cdc. exposure in people who used Survey on Drug Use and Health: gov/tobacco/data_statistics/sgr/ “reduced exposure” tobacco Summary of National Findings, sgr_2004/index.htm. products. J Natl Cancer Inst NSDUH Series H-41, HHS 96:844–852, 2004. Publication No. (SMA) 11-4658. Rockville, MD: Substance

NIDA Research Report Series 11 Where can I get further information about tobacco/nicotine?

To learn more about tobacco/ What’s on the NIDA Web Site Other Web Sites nicotine and other drugs of Information on tobacco • Information on drugs of abuse abuse, visit the NIDA Web and related health consequences addiction is also available site at www.drugabuse.gov or through these Web sites: contact the DrugPubs Research • NIDA publications, news, and events • Centers for Disease Control Dissemination Center at and Prevention: • Resources for health care 877-NIDA-NIH (877-643-2644; www.cdc.gov/tobacco TTY/TDD: 240-645-0228). professionals • Funding information (including • National Cancer Institute: program announcements and www.cancer.gov deadlines) • U.S. Department of Health • International activities and Human Services: www.smokefree.gov • Links to related Web sites (access to Web sites of many • Substance Abuse and Mental other organizations in the field) Health Services Administration Health Information Network: NIDA Web Sites www.samhsa.gov/shin www.drugabuse.gov • Office of the Surgeon General: www.drugabuse.gov/publications/ www.surgeongeneral. term/160/DrugFacts gov/initiatives/tobacco www.easyread.drugabuse.gov • Society for Research on www.drugabuse.gov/blending- Nicotine and Tobacco: www.srnt.org initiative • The Robert Wood Johnson For Physician Information Foundation: www.rwjf.org • Join Together Online: www.drugabuse.gov/nidamed www.quitnet.com • American Legacy Foundation: www.americanlegacy.org

NIH Publication Number 16-4342 Reviewed July 2012. Modified January 2016. This publication is available for your use and may be reproduced in its entirety without permission from NIDA. Citation of the source is appreciated, using the following language: Source: National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services.