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 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, 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. 

Researchers are now also identifying genes that predispose people to 

tobacco addiction and predict their 

response to smoking cessation treatments. These findings—and many 

other recent research accomplishments—present unique opportunities 

to discover, develop, and disseminate 

new treatments for tobacco addiction, 

as well as scientifically based prevention programs to help curtail the 

public health burden that tobacco 

use represents.

We hope this Research Report will 

help readers understand the harmful 

effects of tobacco use and identify 

best practices for the prevention and 

treatment of tobacco addiction.

Nora D. Volkow, M.D.

Director

National Institute on Drug Abuse

Tobacco 

Addiction

What are 

the medical 

consequences 

of tobacco use?

See page 4.

continued inside

According to the 2007 National Survey on Drug Use 

and Health, an estimated 70.9 million Americans aged 

12 or older reported current use of tobacco—60.1 

million (24.2 percent of the population) were current cigarette 

smokers, 13.3 million (5.4 percent) smoked cigars, 8.1 million 

(3.2 percent) used smokeless tobacco, and 2 million (0.8 percent) 

smoked pipes, confirming that tobacco is one of the most widely 

abused substances in the United States. Although the numbers 

of people who smoke are still unacceptably high, according 

What Are the Extent and 

Impact of Tobacco Use?
Research Report Series

to the Centers for Disease 

Control and Prevention there 

has been a decline of almost 

50 percent since 1965.

NIDA’s 2008 Monitoring the 

Future survey of 8th-, 10th-, and 

12th-graders, which is used to track 

drug use patterns and attitudes, has 

also shown a striking decrease 

in smoking trends among the 

Nation’s youth. The latest results 

indicate that about 7 percent of 

8th-graders, 12 percent of 

10th-graders, and 20 percent of 

12th-graders had used cigarettes in 

the 30 days prior to the survey—

the lowest levels in the history of 

the survey. 

The declining prevalence of 

cigarette smoking among the 

general U.S. population, however, is not reflected in patients 

with mental illnesses. The rate of 

smoking in patients suffering from 

post-traumatic stress disorder, 

bipolar disorder, major depression, 

and other mental illness is two- to 

fourfold higher than in the general 

population; and among people 

with schizophrenia, smoking 

rates as high as 90 percent 

have been reported. 

Tobacco use is the leading 

preventable cause of death in the 

United States. The impact of 

tobacco use in terms of morbidity 

and mortality to society is staggering.

Economically, more than 

$96 billion of total U.S. health 

care costs each year are 

attributable directly to smoking. 

However, this is well below the 

total cost to society because it 

does not include burn care from 

smoking-related fires, perinatal 

care for low-birthweight infants of 

mothers who smoke, and medical 

care costs associated with disease 

caused by secondhand smoke. 

In addition to health care costs, 

the costs of lost productivity due 

to smoking effects are estimated 

at $97 billion per year, bringing 

a conservative estimate of the 

economic burden of smoking to 

more than $193 billion per year.

How Does 

Tobacco Deliver 

Its Effects? 

There are more than 4,000 

chemicals found in the smoke 

of tobacco products. Of these, 

nicotine, first identified in the 

early 1800s, is the primary reinforcing component of tobacco. 

Cigarette smoking is the 

most popular method of using 

tobacco; however, there has also 

been a recent increase in the 

use of smokeless tobacco products, such as snuff and chewing 

tobacco. These smokeless products also contain nicotine, as 

well as many toxic chemicals.

The cigarette is a very efficient 

and highly engineered drug delivery system. By inhaling tobacco 

smoke, the average smoker takes 

in 1–2 mg of nicotine per cigarette. When tobacco is smoked, 

nicotine rapidly reaches peak 

levels in the bloodstream and 

enters the brain. A typical smoker 

will take 10 puffs on a cigarette 

over a period of 5 minutes that 

Tobacco 

Addiction

2 NIDA Research Report Series

12th grade

10th grade

8th grade

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Source: University of Michigan, 2008 Monitoring the Future Survey. 

5

10

15

20

25

30

35

40

Percent Reporting Use

Trends in Prevalence of Cigarette Use 

for 8th-, 10th-, and 12th-Graders

Percentage of Students Using Cigarettes Over a 30-Day Period, 1992–2008
the cigarette is lit. Thus, a person 

who smokes about 11⁄2 packs (30 

cigarettes) daily gets 300 “hits” of 

nicotine to the brain each day. In 

those who typically do not inhale 

the smoke—such as cigar and pipe 

smokers and smokeless tobacco 

users—nicotine is absorbed 

through the mucosal membranes 

and reaches peak blood levels 

and the brain more slowly.

Immediately after exposure 

to nicotine, there is a “kick” 

caused in part by the drug’s 

stimulation of the adrenal glands 

and resulting discharge of 

epinephrine (adrenaline). 

The rush of adrenaline stimulates the body and causes an 

increase in blood pressure, 

respiration, and heart rate. 

Is Nicotine 

Addictive?

Yes. Most smokers use tobacco 

regularly because they are addicted 

to nicotine. Addiction is characterized by compulsive drug seeking and abuse, even in the face 

of negative health consequences. 

It is well documented that most 

smokers identify tobacco use 

as harmful and express a desire 

to reduce or stop using it, and 

nearly 35 million of them want 

to quit each year. Unfortunately, 

more than 85 percent of those 

who try to quit on their own 

relapse, most within a week.

Research has shown how nicotine acts on the brain to produce 

a number of effects. Of primary 

importance to its addictive nature 

are findings that nicotine activates 

reward pathways—the brain circuitry that regulates feelings of 

pleasure. A key brain chemical 

involved in mediating the desire to 

consume drugs is the neurotransmitter dopamine, and research 

has shown that nicotine increases 

levels of dopamine in the reward 

circuits. This reaction is similar to 

that seen with other drugs of abuse 

and is thought to underlie the pleasurable sensations experienced by 

many smokers. For many tobacco 

users, long-term brain changes 

induced by continued nicotine 

exposure result in addiction.

Nicotine’s pharmacokinetic 

properties also enhance its abuse 

potential. Cigarette smoking 

produces a rapid distribution of 

nicotine to the brain, with drug 

levels peaking within 10 seconds 

of inhalation. However, the 

acute effects of nicotine dissipate 

quickly, as do the associated feelings of reward, which causes the 

smoker to continue dosing to 

maintain the drug’s pleasurable 

effects and prevent withdrawal.

Nicotine withdrawal symptoms include irritability, craving, 

depression, anxiety, cognitive 

and attention deficits, sleep disturbances, and increased appetite. These symptoms may begin 

within a few hours after the last 

cigarette, quickly driving people 

back to tobacco use. Symptoms 

peak within the first few days of 

smoking cessation and usually 

subside within a few weeks. For 

some people, however, symptoms may persist for months.

Although withdrawal is related 

to the pharmacological effects 

of nicotine, many behavioral 

factors can also affect the severity of withdrawal symptoms. For 

some people, the feel, smell, and 

sight of a cigarette and the ritual 

of obtaining, handling, lighting, 

and smoking the cigarette are all 

associated with the pleasurable 

effects of smoking and can make 

withdrawal or craving worse. 

Nicotine replacement therapies 

such as gum, patches, and inhalers 

may help alleviate the pharmacological aspects of withdrawal; 

however, cravings often persist. 

Behavioral therapies can help smokers identify environmental triggers 

of craving so they can employ 

strategies to prevent or circumvent these symptoms and urges. 

Tobacco plants

Most smokers 

identify tobacco 

use as harmful and 

express a desire 

to reduce or stop 

using it, and nearly 

35 million want to 

quit each year. 

NIDA Research Report Series 3
Are There Other 

Chemicals That 

May Contribute 

to Tobacco 

Addiction? 

Yes, research is showing that nicotine may not be the only ingredient 

in tobacco that affects its addictive 

potential. Using advanced neuroimaging technology, scientists can 

see the dramatic effect of cigarette 

smoking on the brain and are finding a marked decrease in the levels 

of monoamine oxidase (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 NIDAfunded researchers have shown 

that acetaldehyde, another 

chemical found in tobacco 

smoke, dramatically increases 

the reinforcing properties of 

nicotine and may also contribute 

to tobacco addiction. The investigators further report that this 

effect is age-related: adolescent 

animals display far more sensitivity to this reinforcing effect, 

which suggests that the brains 

of adolescents may be more vulnerable to tobacco addiction.

What Are 

the Medical 

Consequences 

of Tobacco Use?

Cigarette smoking kills an estimated 440,000 U.S. citizens each 

year—more than alcohol, illegal 

drug use, homicide, suicide, car 

accidents, and AIDS combined. 

Between 1964 and 2004, more 

than 12 million Americans died 

prematurely from smoking, and 

another 25 million U.S. smokers alive today will most likely 

die of a smoking-related illness. 

Cigarette smoking harms nearly 

every organ in the body. It has been 

conclusively linked to cataracts and 

pneumonia, and accounts for about 

one-third of all cancer deaths. The 

overall rates of death from cancer 

are twice as high among smokers 

as nonsmokers, with heavy smokers having rates that are four times 

greater than those of nonsmokers. Foremost among the cancers 

caused by tobacco use is lung 

cancer—cigarette smoking has 

been linked to about 90 percent of 

all cases of lung cancer, the number 

one cancer killer of both men and 

women. Smoking is also associated 

with cancers of the mouth, pharynx, larynx, esophagus, stomach, 

pancreas, cervix, kidney, bladder, 

and acute myeloid leukemia. 

In addition to cancer, smoking causes lung diseases such as 

chronic bronchitis and emphysema, 

and it has been found to exacerbate 

asthma symptoms in adults and 

children. About 90 percent of all 

deaths from chronic obstructive 

pulmonary diseases are attributable to cigarette smoking. It has 

also been well documented that 

smoking substantially increases 

the risk of heart disease, including stroke, heart attack, vascular 

Nicotine replacement 

therapies such as gum, 

patches, and inhalers 

may help alleviate 

the pharmacological 

aspects of withdrawal.

Using advanced neuroimaging technology, scientists can see the dramatic effect of 

cigarette smoking on the brain and body and are finding a marked decrease in the 

levels of monoamine oxidase (MAO B), an important enzyme that is responsible for 

the breakdown of dopamine. (Source: Fowler et al., 2003)

4 NIDA Research Report Series
disease, and aneurysm. Smoking causes coronary heart disease, the leading cause of death 

in the United States: cigarette 

smokers are 2–4 times more 

likely to develop coronary heart 

disease than nonsmokers.

Exposure to high doses of 

nicotine, such as those found in 

some insecticide sprays, can be 

extremely toxic as well, causing vomiting, tremors, convulsions, and death. In fact, one 

drop of pure nicotine can kill 

a person. Nicotine poisoning 

has been reported from accidental ingestion of insecticides 

by adults and ingestion of 

tobacco products by children 

and pets. Death usually results 

in a few minutes from respiratory failure caused by paralysis.

Although we often think 

of medical consequences that 

result from direct use of tobacco 

products, passive or secondary 

smoke also increases the risk for 

many diseases. Environmental 

tobacco smoke is a major source 

of indoor air contaminants; secondhand smoke is estimated to 

cause approximately 3,000 lung 

cancer deaths per year among 

nonsmokers and contributes to 

more than 35,000 deaths related 

to cardiovascular disease. Exposure to tobacco smoke in the 

home is also a risk factor for 

new cases and increased severity of childhood asthma. Additionally, dropped cigarettes are 

the leading cause of residential 

fire fatalities, leading to more 

than 1,000 deaths each year.

Sticky, brown tar coats the 

lungs of tobacco smokers. 

Along with thousands of 

other damaging chemicals, 

tar can lead to lung cancer 

and acute respiratory 

diseases.

NIDA Research Report Series 5

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 not 

yet been evaluated sufficiently 

to determine whether they are 

indeed associated with reduced 

risk of disease. Recent studies 

indicate that the levels of carcinogens in these PREPs range from 

relatively low to comparable to 

conventional tobacco products. 

These studies conclude that 

medicinal nicotine (found in the 

nicotine patch and gum) is a safer 

alternative than these modified 

tobacco products.
Smoking and 

Pregnancy—

What Are 

the Risks?

In the United States, it is estimated that about 16 percent of 

pregnant women smoke during 

their pregnancies. Carbon monoxide and nicotine from tobacco 

smoke may interfere with the oxygen supply to the fetus. Nicotine 

also readily crosses the placenta, 

and concentrations in the fetus 

can be as much as 15 percent 

higher than maternal levels.

Nicotine concentrates in fetal 

blood, amniotic fluid, and breast 

milk. Combined, these factors 

can have severe consequences 

for the fetuses and infants of 

smoking mothers. Smoking 

during pregnancy caused an 

estimated 910 infant deaths 

annually from 1997 through 2001, 

and neonatal care costs related 

to smoking are estimated to be 

more than $350 million per year.

 The adverse effects of smoking 

during pregnancy can include fetal 

growth retardation and decreased 

birthweight. The decreased birthweights seen in infants of mothers 

who smoke reflect a dose-dependent relationship—the more the 

woman smokes during pregnancy, 

the greater the reduction of infant 

birthweight. These newborns 

also display signs of stress and 

drug withdrawal consistent 

with what has been reported in 

infants exposed to other drugs. 

In some cases, smoking during 

pregnancy may be associated 

with spontaneous abortions and 

sudden infant death syndrome 

(SIDS), as well as learning 

and behavioral problems and 

an increased risk of obesity in 

children. 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.

There is clear evidence of high rates of psychiatric 

comorbidity, including other substance abuse, 

among adolescents and adults who smoke. For 

example, it has been estimated that individuals 

with psychiatric disorders purchase approximately 

44 percent of all cigarettes sold in the United States, 

which undoubtedly contributes to the disproportionate rates of morbidity and mortality in these populations. In addition, studies have shown that as many 

as 80 percent of alcoholics smoke regularly, and that 

a majority of them will die of smoking-related, rather 

than alcohol-related, disease. 

In young smokers, the behavior appears to be 

strongly associated with increased risk for a variety 

of mental disorders. In some cases—such as with 

conduct disorders and attention-deficit hyperactivity 

disorder—these disorders may precede the onset of 

smoking, while in others—such as with substance 

abuse—the disorders may emerge later in life. 

Whether daily smoking among boys and girls is the 

result or the cause of a manifest psychiatric condition, 

it is troubling that so very few adolescents have their 

nicotine dependence diagnosed or properly treated. 

Preventing the early onset of smoking and treating its 

young victims are critical primary-care priorities, the 

fulfillment of which could have a dramatic impact on 

our ability to prevent or better address a wide range 

of mental disorders throughout life. 

Among adults, the rate of major depressive episodes is highest in nicotine-dependent individuals, 

lower in nondependent current smokers, and lowest 

in those who quit or never started smoking. Furthermore, there is evidence showing that, for those who 

have had more than one episode, smoking cessation 

may increase the likelihood of a new major depressive episode. Adult tobacco use also increases 

risk for the later development of anxiety disorders, 

which may be associated with an increased severity 

of withdrawal symptoms during smoking cessation 

therapy. But the most extensive comorbidity overlap 

is likely the one that exists between smoking and 

schizophrenia, since, in clinical samples, the rate of 

smoking in patients with schizophrenia has ranged 

as high as 90 percent.

Tobacco Use and Comorbidity

6 NIDA Research Report Series
Smoking and Adolescence

In 2007, more than 3 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 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.

Adolescents may also be more sensitive to the reinforcing effects of 

nicotine in combination with other chemicals found in cigarettes, thus 

increasing susceptibility to tobacco addiction. As mentioned above, 

acetaldehyde increases nicotine’s addictive properties in adolescent, 

but not adult, animals. A recent study also suggests that specific genes 

may increase risk for addiction among people who begin smoking during 

adolescence. NIDA continues to actively support research aimed 

at increasing our understanding of why and how adolescents become 

addicted, and to develop prevention and treatment strategies to meet 

their specific needs.

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 differently, such as social factors or 

the sensory aspects of smoking.

The number of smokers in the 

United States declined in the 1970s 

and 1980s, remained relatively 

stable throughout the 1990s, and 

Large-scale smoking 

cessation trials show 

that women are 

less likely to initiate 

quitting and may be 

more likely to relapse 

if they do quit. 

NIDA Research Report Series 7
declined further through the early 

2000s. Because this decline in 

smoking was greater among men 

than women, the prevalence of 

smoking is only slightly higher for 

men today than it is for women. 

Several factors appear to be 

contributing to this narrowing 

gender gap, including women 

being less likely than men to quit.

Large-scale smoking cessation 

trials show that women are less 

likely to initiate quitting and may 

be more likely to relapse if they 

do quit. In cessation programs 

using nicotine replacement methods, such as the patch or gum, the 

nicotine does not seem to reduce 

craving as effectively for women 

as for men. Other factors that 

may contribute to women’s difficulty with quitting 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, they were more successful at quitting than women who 

were in a program designed only 

to attenuate postcessation weight 

gain. Other NIDA researchers 

have found that medications 

used for smoking cessation, 

such as bupropion and naltrexone, can also attenuate postcessation weight gain and could 

become an additional strategy 

for enhancing treatment success. 

It is important for treatment 

professionals to be aware that 

standard regimens may have to be 

adjusted to compensate for gender 

differences in nicotine sensitivity 

and in other related factors that 

contribute to continued smoking.

Are There 

Effective 

Treatments 

for Tobacco 

Addiction?

Yes, extensive research has shown 

that treatments for tobacco 

addiction do work. Although 

some smokers can quit without 

help, many individuals need 

assistance with quitting. This is 

particularly important because 

smoking cessation can have 

immediate health benefits. For 

example, within 24 hours of 

quitting, blood pressure and 

chances of heart attack decrease. 

Long-term benefits of smoking 

cessation include decreased risk 

of stroke, lung and other cancers, 

and coronary heart disease. 

A 35-year-old man who quits 

smoking will, on average, increase 

his life expectancy by 5 years.

Nicotine Replacement 

Treatments

Nicotine replacement therapies 

(NRTs), such as nicotine gum and 

the transdermal nicotine patch, 

were the first pharmacological 

treatments approved by the Food 

and Drug Administration (FDA) 

for use in smoking cessation therapy. NRTs are used (in conjunction 

with behavioral support) to relieve 

withdrawal symptoms—they 

produce less severe physiological 

alterations than tobacco-based 

systems and generally provide 

users with lower overall nicotine levels than they receive with 

tobacco. An added benefit is that 

these forms of nicotine have little 

abuse potential since they do not 

produce the pleasurable effects 

of tobacco products, nor do they 

contain the carcinogens and gases 

associated with tobacco smoke. 

Behavioral treatments, even beyond 

what is recommended on packaging labels, have been shown to 

enhance the effectiveness of NRTs 

and improve long-term outcomes.

The FDA’s approval of nicotine 

gum in 1984 marked the availability (by prescription) of the first 

NRT on the U.S. market. In 1996, 

the FDA approved Nicorette gum 

for over-the-counter (OTC) sales. 

Whereas nicotine gum provides 

some smokers with the desired 

control over dose and the ability to 

relieve cravings, others are unable 

to tolerate the taste and chewing 

demands. In 1991 and 1992, the 

FDA approved four transdermal 

Smoking cessation can 

have immediate health 

benefits. For example, 

within 24 hours of 

quitting, blood pressure 

and chances of heart 

attack decrease. 

8 NIDA Research Report Series
nicotine patches, two of which 

became OTC products in 1996. 

In 1996 a nicotine nasal spray, 

and in 1998 a nicotine inhaler, 

also became available by prescription, thus meeting the needs of 

many additional tobacco users. 

All the NRT products—gum, 

patch, spray, and inhaler—appear 

to be equally effective. 

Additional Medications

Although the primary focus of 

pharmacological treatments for 

tobacco addiction has been nicotine replacement, other treatments 

are also available. For example, 

the antidepressant bupropion was 

approved by the FDA in 1997 to 

help people quit smoking and is 

marketed as Zyban. Varenicline 

tartrate (Chantix) is a medication that recently received FDA 

approval for smoking cessation. 

This medication, which acts at 

the sites in the brain affected by 

nicotine, may help people quit 

by easing withdrawal symptoms 

and blocking the effects of nicotine if people resume smoking.

Several other nonnicotine 

medications are being investigated 

for the treatment of tobacco addiction, including other antidepressants and an antihypertensive 

medication. Scientists are also 

investigating the potential of a 

vaccine that targets nicotine for 

use in relapse prevention. The 

nicotine vaccine is designed to 

stimulate the production of antibodies that would block access of 

nicotine to the brain and prevent 

nicotine’s reinforcing effects.

Behavioral Treatments

Behavioral interventions play an 

integral role in smoking cessation 

treatment, either in conjunction 

with medication or alone. A variety of methods can assist smokers with quitting, ranging from 

self-help materials to individual 

cognitive-behavioral therapy. These 

interventions teach individuals to 

recognize high-risk smoking situations, develop alternative coping 

strategies, manage stress, improve 

problemsolving skills, and increase 

social support. Research has also 

shown that the more therapy is 

tailored to a person’s situation, the 

greater the chances are for success. 

Traditionally, behavioral 

approaches were developed and 

delivered through formal settings, 

such as smoking cessation clinics and community and public 

health settings. Over the past 

decade, however, researchers have 

been adapting these approaches 

for mail, telephone, and Internet 

formats, which can be more acceptable and accessible to smokers 

who are trying to quit. In 2004, 

the U.S. Department of Health 

and Human Services (HHS) established a national toll-free number, 

800-QUIT-NOW (800-784-8669), 

to serve as a single access point 

for smokers seeking information 

and assistance in quitting. Callers 

to the number are routed to their 

State’s smoking cessation quitline 

or, in States that have not established quitlines, to one maintained 

by the National Cancer Institute. 

In addition, a new HHS Web site 

(www.smokefree.gov) offers online 

advice and downloadable information to make cessation easier. 

Quitting smoking can be 

difficult. People can be helped 

during the time an intervention 

is delivered; however, most intervention programs are short-term 

(1–3 months). Within 6 months, 

75–80 percent of people who try 

to quit smoking relapse. Research 

has now shown that extending 

treatment beyond the typical 

duration of a smoking cessation 

program can produce quit rates 

as high as 50 percent at 1 year.

NIDA Research Report Series 9

Twin studies indicate 

that approximately 

40–70 percent of 

a person’s risk of 

becoming addicted 

to nicotine depends 

on his or her genes. 
New Frontiers 

in Tobacco 

Research

If so many smokers want to quit, 

why are few able to do so successfully? To address this question, 

scientists are increasingly focusing 

on the powerful role of genetics in 

addiction. Twin studies indicate 

that approximately 40–70 percent 

of a person’s risk of becoming 

addicted to nicotine depends on 

his or her genes. Although complex 

diseases like addiction involve large 

numbers of genes interacting with 

a wide variety of environmental 

factors, the contribution of a 

particular gene can be substantial: 

Genetic variants associated with 

nicotine metabolism, for example, 

have been shown to influence 

how people smoke such that slow 

metabolizers smoke fewer cigarettes per day and have a higher 

likelihood of quitting, and that 

there is greater abstinence among 

individuals receiving nicotine 

patch therapy. A recent NIDAfunded study identified a variant 

in the gene for a nicotinic receptor 

subunit that doubled the risk for 

nicotine addiction among smokers. 

A subsequent study found that this 

gene variant also increased susceptibility to the severe health consequences of smoking, including 

lung cancer and peripheral arterial 

disease. NIDA is currently supporting large-scale genome-wide association studies to uncover additional 

genetic risk factors in order to better understand tobacco addiction 

and its adverse effects on health. 

In addition to predicting an 

individual’s risk for nicotine 

addiction, genetic markers can 

also help predict whether medications (like bupropion) will effectively help a smoker quit. This 

takes root in the emerging field 

of pharmacogenomics, which 

investigates how genes influence 

a patient’s response to drugs and 

medications. In the future, genetic 

screening could help clinicians 

select treatments, adjust dosages, 

and avoid or minimize adverse 

reactions, tailoring smoking cessation therapies to an individual’s 

unique genetic inheritance.

Glossary

Addiction: A chronic, relapsing 

disease characterized by compulsive drug seeking and abuse and 

by long-lasting neurochemical and 

molecular changes in the brain.

Adrenal glands: Glands located 

above each kidney that secrete 

hormones, e.g., adrenaline.

Craving: A powerful, often uncontrollable desire for drugs.

Dopamine: A neurotransmitter 

present in regions of the brain that 

regulate movement, emotion, motivation, and feelings of pleasure.

Emphysema: A lung disease in 

which tissue deterioration results 

in increased air retention and 

reduced exchange of gases. The 

result is difficulty breathing and 

shortness of breath. 

Neurotransmitter: A chemical that 

acts as a messenger to carry signals or information from one nerve 

cell to another. 

Nicotine: An alkaloid derived from 

the tobacco plant that is primarily 

responsible for smoking’s psychoactive and addictive effects.

Pharmacokinetics: The pattern 

of absorption, distribution, and 

excretion of a drug over time.

Tobacco: A plant widely cultivated 

for its leaves, which are used primarily for smoking; the N. tabacum

species is the major source of 

tobacco products.

Withdrawal: A variety of symptoms that occur after chronic use 

of an addictive drug is reduced 

or stopped.

10 NIDA Research Report Series
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Merritt, R. Neonatal health care costs 

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Belluzzi, J.D.; Wang, R.; and Leslie, 

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Benowitz, N.L. Pharmacology of 

nicotine: Addiction and therapeutics. 

Ann Rev Pharmacol Toxicol 36:597–

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Buka, S.L.; Shenassa, E.D.; and 

Niaura, R. Elevated risk of tobacco 

dependence among offspring of mothers who smoked during pregnancy: 

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NIDA Research Report Series 11
NIH Publication Number 09-4342

Printed July 1998, Reprinted August 2001, Revised July 2006,

Revised June 2009

Feel free to reprint this publication.

Where Can I Get More Scientific Information on 

Tobacco Addiction?

To learn more about tobacco and other drugs of 

abuse, or to order materials on these topics free 

of charge in English or Spanish, visit the NIDA 

Web site at www.drugabuse.gov or contact

the DrugPubs Research Dissemination Center 

at 877-NIDA-NIH (877-643-2644; 

TTY/TDD: 240-645-0228).

What’s New on the NIDA Web Site

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NIDA Web Sites

drugabuse.gov

backtoschool.drugabuse.gov

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For Physician Information

www.drugabuse.gov/nidamed

Other Web Sites

Information on tobacco addiction is also 

available through these other Web sites:

•	 Centers for Disease Control and Prevention:

www.cdc.gov/tobacco

•	 National Cancer Institute: www.cancer.gov

•	 U.S. Department of Health and Human Services:

www.smokefree.gov

•	 Substance Abuse and Mental Health Services

Administration Health Information Network: 

www.samhsa.gov/shin

•	 Society for Research on Nicotine and Tobacco:

www.srnt.org

•	 NicNet: www.nicnet.org

•	 The Robert Wood Johnson Foundation:

www.rwjf.org

•	 Join Together Online: www.quitnet.org

•	 American Legacy Foundation:

www.americanlegacy.org