Tobaccorrsv3

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/
Nicotine
What are
the medical
consequences
of tobacco use?
See page 4.
continued inside
A
ccording to the 2010 National Survey on Drug Use
and Health, an estimated 69.6 million Americans aged
12 or older reported current use of tobacco — 58.3
million (23.0 percent of the population) were current cigarette
smokers, 13.2 million (5.2 percent) smoked cigars, 8.9 million
(3.5 percent) used smokeless tobacco, and 2.2 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 to the Centers for Disease Control and Prevention
there has been a decline of almost 50 percent since 1965.
What Are the Extent and
Impact of Tobacco Use?

Research Report Series
NIDA’s 2011 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 6 percent of 8th-graders,
12 percent of 10th-graders, and
19 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 illnesses is twofold 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. healthcare 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 healthcare
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 7,000
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, many people also use
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
milligrams 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 the cigarette is lit.
Thus, a person who smokes about
1½ packs (30 cigarettes) daily gets
300 “hits” of nicotine to the brain
each day. In those who typically
Tobacco/
Nicotine
2 NIDA Research Report Series
12th grade
10th grade
8th grade
07 08 09 10 110605040302012000999897961995
Source: University of Michigan, 2011 Monitoring the Future Survey.
5
10
15
20
25
30
35
40
PercentReportingUse
Trends in Prevalence of Cigarette Use
for 8th-, 10th-, and 12th-Graders
Percentage of Students Using Cigarettes Over a 30-Day Period, 1995–2011

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 NIDA-
funded 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,
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), an important enzyme that is responsible for
the breakdown of dopamine. (Source: Fowler et al., 2003)
NIDA Research Report Series4

heart attack, vascular 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
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.
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 conven-
tional products. These “poten-
tially 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 carcino-
gens 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.

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.
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.
There is clear evidence of high rates of psychiat-
ric 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 disproportion-
ate rates of morbidity and mortality in these popula-
tions. 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 condi-
tion, 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 pri-
orities, 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 epi-
sodes is highest in nicotine-dependent individuals,
lower in nondependent current smokers, and lowest
in those who quit or never started smoking. Further-
more, there is evidence showing that, for those who
have had more than one episode, smoking cessation
may increase the likelihood of a new major depres-
sive 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

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.
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 earlier,
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.
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
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.

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 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
Smoking cessation can
have immediate health
benefits. For example,
within 24 hours of
quitting, blood pressure
and chances of heart
attack decrease.

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 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 non-nicotine
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
Twin studies indicate
that approximately
40–70 percent of
a person’s risk of
becoming addicted
to nicotine depends
on his or her genes.

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.
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. Slow metabolizers
smoke fewer cigarettes per day and
have a higher likelihood of quitting,
and there is greater abstinence
among individuals receiving
nicotine patch therapy. A recent
NIDA-funded 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 despite
adverse consequences. It is
associated with long-lasting changes
in the brain.
Adrenal glands: Glands located
above each kidney that secrete
hormones, e.g., adrenaline.
Carcinogen: Any substance that
causes cancer.
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.

Adams, E.K.; Miller, V.P.; Ernst, C.;
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References

NIH Publication Number 12-4342
Printed July 1998, Reprinted August 2001, Revised July 2006,
Revised June 2009, Revised July 2012.
Feel free to reprint this publication.
To learn more about tobacco/
nicotine and other drugs of
abuse, 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).
Where can I get further information about
tobacco/nicotine?
What’s on the NIDA Web Site
• Information on drugs of abuse
and related health consequences
• NIDA publications, news, and
events
• Resources for health care
professionals
• Funding information (including
program announcements and
deadlines)
• International activities
• Links to related Web sites
(access to Web sites of many
other organizations in the field)
NIDA Web Sites
www.drugabuse.gov
www.drugabuse.gov/publications/
term/160/DrugFacts
www.easyread.drugabuse.gov
www.drugabuse.gov/blending-
initiative
For Physician Information
www.drugabuse.gov/nidamed
Other Web Sites
Information on tobacco
addiction is also available
through these 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
• Office of the Surgeon General:
www.surgeongeneral.
gov/initiatives/tobacco
• Society for Research on
Nicotine and Tobacco:
www.srnt.org
• The Robert Wood Johnson
Foundation:
www.rwjf.org
• Join Together Online:
www.quitnet.com
• American Legacy Foundation:
www.americanlegacy.org

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