Research Report

Revised May 2022

Tobacco, Nicotine, and E-Cigarettes Research

Report

Table of Contents
Tobacco, Nicotine, and E-Cigarettes Research Report
Introduction

What is the scope of tobacco, nicotine, and e-cigarette use in the United States?

How does tobacco deliver its effects?

Is nicotine addictive?

What are the physical health consequences of tobacco use?

What are the effects of secondhand and thirdhand tobacco smoke?

What are the risks of smoking during pregnancy?

How many adolescents use tobacco?

What are electronic cigarettes?

Other Tobacco Products

Are there gender differences in tobacco smoking?

Do people with mental illness and substance use disorders use tobacco more often?

What are treatments for tobacco dependence?

How can we prevent tobacco use?

What research is being done on tobacco use?

References

Where can I get further information about tobacco/nicotine?

Tobacco, Nicotine, and E-Cigarettes Research Report
All materials appearing in the ?Research Reports series are in the public domain and may be
reproduced without permission from NIDA. Citation of the source is appreciated.

Introduction
In 2014, the Nation marked the 50th anniversary of the first Surgeon General’s Report on Smoking
and Health. In 1964, more than 40 percent of the adult population smoked. Once the link between
smoking and its medical consequences—including cancers and heart and lung diseases—became a
part of the public consciousness, education efforts and public policy changes were enacted to reduce
the number of people who smoke. These efforts resulted in substantial declines in smoking rates in the
1
United States—to half the 1964 level.
2
However, rates of cigarette smoking and other tobacco use are still too high, and some populations
are disproportionately affected by tobacco’s health consequences. Most notably, people with mental
3–6
disorders—including substance use disorders—smoke at higher rates than the general population.
Additionally, people living below the poverty line and those with low educational attainment are more
likely to smoke than those in the general population. As tobacco use is the leading preventable cause
1
of mortality in the United States, differential rates of smoking and use of other tobacco products is a
significant contributor to health disparities among some of the most vulnerable people in our society.

What is the scope of tobacco, nicotine, and e-cigarette use in

the United States?
All data refer to the United States population.

How many people use tobacco products or vaping devices?

Among people aged 12 or older in 2020:
 20.7% (or about 57.3 million people) reported using tobacco products or vaping nicotine in the
past 30 days.
15.0% (or about 41.4 million people) reported smoking cigarettes in the past 30 days.
3.8% (or about 10.4 million people) reported vaping nicotine in the past 30 days.

Source: 2020 National Survey on Drug Use and Health

How many young students use tobacco products or vaping devices?

Among young people in 2021:
th th th
An estimated 9.4% of 8 graders and 15.7% of 10 graders, and 24.6% of 12 graders reported
any nicotine use in the past 30 days.
th th th
An estimated 1.1% of 8 graders, 1.8% of 10 graders, and 4.1% of 12 graders reported any
cigarette use in the past 30 days.
th th th
An estimated 7.6% of 8 graders, 13.1% of 10 graders, and 19.6% of 12 graders reported
vaping nicotine in the past 30 days.

Source: 2021 Monitoring the Future Survey

How many people have a nicotine dependence?

Among people aged 12 or older in 2020, 8.5% (or about 23.6 million people) had nicotine
dependence in the past 30 days.

Source: 2020 National Survey on Drug Use and Health

How does tobacco deliver its effects?

The smoke from combustible tobacco products contains more than 7,000 chemicals. Nicotine is the
20,21
primary reinforcing component of tobacco; it drives tobacco addiction. Hundreds of compounds are
22
added to tobacco to enhance its flavor and the absorption of nicotine. Cigarette smoking is the most
popular method of using tobacco; however, many people also use smokeless tobacco products, such
as snuff and chewing tobacco, which also contain nicotine (see "Other Tobacco Products"). E-

Page 3
cigarettes, which deliver nicotine in the absence of other chemicals in tobacco, have become popular
in recent years (see "What are electronic cigarettes?").

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
23
smoker will take 10 puffs on a cigarette over the roughly 5 minutes that the cigarette is lit. Thus, a
person who smokes about 1 pack (20 cigarettes) daily gets 200 "hits" of nicotine to the brain each day.
Among those who do not inhale the smoke—such as cigar and pipe smokers and smokeless tobacco
users—nicotine is absorbed through mucous membranes in the mouth and reaches peak blood and
brain levels 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
24
the body and causes an increase in blood pressure, respiration, and heart rate. Like other drugs,
nicotine also activates reward pathways in the brain—circuitry that regulates reinforcement and
20,21
feelings of pleasure.

Is nicotine addictive?
Yes. Most smokers use tobacco regularly because they are addicted to nicotine. Addiction is
characterized by compulsive drug-seeking and use, even in the face of negative health consequences.
The majority of smokers would like to stop smoking, and each year about half try to quit permanently.
25
Yet, only about 6 percent of smokers are able to quit in a given year. Most smokers will need to
22
make multiple attempts before they are able to quit permanently. Medications including varenicline,
and some antidepressants (e.g. bupropion), and nicotine-replacement therapy, can help in many
26
cases (see "What are treatments for tobacco dependence?").

A transient surge of endorphins in the reward circuits of the brain causes a slight, brief euphoria when
nicotine is administered. This surge is much briefer than the "high" associated with other drugs.
However, like other drugs of abuse, nicotine increases levels of the neurotransmitter dopamine in
20,21,27
these reward circuits, which reinforces the behavior of taking the drug. Repeated exposure

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alters these circuits' sensitivity to dopamine and leads to changes in other brain circuits involved in
learning, stress, and self-control. For many tobacco users, the long-term brain changes induced by
continued nicotine exposure result in addiction, which involves withdrawal symptoms when not
28,29
smoking, and difficulty adhering to the resolution to quit.

The pharmacokinetic properties of nicotine, or the way it is processed by the body, contribute to its
24
addictiveness. When cigarette smoke enters the lungs, nicotine is absorbed rapidly in the blood and
delivered quickly to the brain, so that nicotine levels peak within 10 seconds of inhalation. But the
acute effects of nicotine also dissipate quickly, along with the associated feelings of reward; this rapid
cycle causes the smoker to continue dosing to maintain the drug's pleasurable effects and prevent
30
withdrawal symptoms.

Withdrawal occurs as a result of dependence, when the body becomes used to having the drug in the
system. Being without nicotine for too long can cause a regular user to experience irritability, craving,
depression, anxiety, cognitive and attention deficits, sleep disturbances, and increased appetite.
These withdrawal symptoms may begin within a few hours after the last cigarette, quickly driving
people back to tobacco use.

When a person quits smoking, withdrawal symptoms peak within the first few days of the last cigarette
31
smoked and usually subside within a few weeks. For some people, however, symptoms may persist
for months, and the severity of withdrawal symptoms appears to be influenced by a person's genes.
30,31

In addition to its pleasurable effects, nicotine also temporarily boosts aspects of cognition, such as the
ability to sustain attention and hold information in memory. However, long-term smoking is associated
with cognitive decline and risk of Alzheimer's Disease, suggesting that short-term nicotine-related
32
enhancement does not outweigh long-term consequences for cognitive functioning. In addition,
people in withdrawal from nicotine experience neurocognitive deficits such as problems with attention
33
or memory. These neurocognitive withdrawal symptoms are increasingly recognized as a contributor
34
to continued smoking. A small research study also suggested that withdrawal may impair sleep for
35
severely dependent smokers, and that this may additionally contribute to relapse.
30
In addition to the drug's impact on multiple neurotransmitters and their receptors, many behavioral
factors can affect the severity of withdrawal symptoms. For many people who smoke, the feel, smell,

Page 5
and sight of a cigarette and the ritual of obtaining, handling, lighting, and smoking the cigarette are all
36
associated with the pleasurable effects of smoking and can make withdrawal or craving worse.
Learning processes in the brain associate these cues with nicotine-induced dopamine surges in the
21
reward system —similar to what occurs with other drug addictions. Nicotine replacement therapies
such as gum, patches, and inhalers, and other medications approved for the treatment of nicotine
37–39
addiction may help alleviate the physiological aspects of withdrawal (see "What are treatments for
tobacco dependence?"); however, cravings often persist because of the power of these cues.
Behavioral therapies can help smokers identify environmental triggers of craving so they can use
40,41
strategies to avoid these triggers and manage the feelings that arise when triggers cannot be.

Are there other chemicals that may contribute to tobacco addiction?

Research is showing that nicotine may not be the only ingredient in tobacco that affects its
addictive potential.

Smoking is linked with a marked decrease in the levels of monoamine oxidase (MAO), an
important enzyme that is responsible for the breakdown of dopamine, as well as a reduction in
42
MAO binding sites in the brain. This change is likely caused by some as-yet-unidentified
ingredient in tobacco smoke other than nicotine, because we know that nicotine itself does not
dramatically alter MAO levels. Animal research suggests that MAO inhibition makes nicotine more
reinforcing, but more studies are needed to determine whether MAO inhibition affects human
42
tobacco dependence.

Animal research has also shown that acetaldehyde, another chemical in tobacco smoke created
by the burning of sugars added as sweeteners, dramatically increases the reinforcing properties
43
of nicotine and may also contribute to tobacco addiction.

What are the physical health consequences of tobacco use?

1,44
Cigarette smoking harms nearly every organ in the body, and smoking is the leading preventable
cause of premature death in the United States. Although rates of smoking have declined, it is

Page 6
 1
estimated that it leads to about 480,000 deaths yearly. Smokers aged 60 and older have a twofold
increase in mortality compared with those who have never smoked, dying an estimated 6 years earlier.
45
Quitting smoking results in immediate health benefits, and some or all of the reduced life
46
expectancy can be recovered depending on the age a person quits.

Although nicotine itself does not cause cancer, at least 69 chemicals in tobacco smoke are
1
carcinogenic, and cigarette smoking accounts for at least 30 percent of all cancer deaths.22 The
overall rates of death from cancer are twice as high among smokers as nonsmokers, with heavy
1
smokers having a four times greater risk of death from cancer than nonsmokers.

Foremost among the cancers caused by tobacco use is lung cancer. Cigarette smoking has been
linked to about 80 to 90 percent of all cases of lung cancer, the leading cause of cancer death for both
22,47
men and women, and it is responsible for roughly 80 percent of deaths from this disease. Smoking
48
increases lung cancer risk five to tenfold, with greater risk among heavy smokers. Smoking is also
associated with cancers of the mouth, pharynx, larynx, esophagus, stomach, pancreas, cervix, kidney,
1
and bladder, as well as acute myeloid. Cigarette smoking is not the only form of tobacco use
associated with cancers. Smokeless tobacco (see "Other Tobacco Products") has been linked to
49
cancer of the pharynx, esophagus, stomach, and lung, as well as to colorectal cancer.

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. Cigarette smoking is the
50
most significant risk factor for chronic obstructive pulmonary disease (COPD). Survival statistics
indicate that quitting smoking results in repair to much of the smoking-induced lung damage over time.
However, once COPD develops, it is irreversible; COPD-related lung damage is not repaired with time.

Smoking also substantially increases the risk of heart disease, including stroke, heart attack, vascular
51,52
disease, and aneurysm. Cardiovascular disease is responsible for 40 percent of all smoking-
53
related deaths. Smoking causes coronary heart disease, the leading cause of death in the United
States. Smoking is also linked to many other major health conditions—including rheumatoid arthritis,
inflammation, and impaired immune function.1 Even young smokers aged 26 to 41 report reduced
health-related quality of life compared with nonsmoking peers, according to a cross-sectional
54
population study. Recent animal research also identified a pathway between the pancreas and a
part of the brain active in nicotine intake, potentially linking cigarette smoking to the risk of developing
Type 2 Diabetes.

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What are the effects of secondhand and thirdhand tobacco
smoke?
Secondhand smoke is a significant public health concern and driver of smoke-free policies. Also called
55
passive or secondary smoke, secondhand smoke increases the risk for many diseases. Exposure to
48
environmental tobacco smoke among nonsmokers increases lung cancer risk by about 20 percent.
Secondhand smoke is estimated to cause approximately 53,800 deaths annually in the United States.
55 56
Exposure to tobacco smoke in the home is also a risk factor for asthma in children.

Smoking also leaves chemical residue on surfaces where smoking has occurred, which can persist
long after the smoke itself has been cleared from the environment. This phenomenon, known as
"thirdhand smoke," is increasingly recognized as a potential danger, especially to children, who not
only inhale fumes released by these residues but also ingest residues that get on their hands after
crawling on floors or touching walls and furniture. More research is needed on the risks posed to
humans by thirdhand smoke, but a study in mice showed that thirdhand smoke exposure has several
behavioral and physical health impacts, including hyperactivity and adverse effects on the liver and
57
lungs.

What are the risks of smoking during pregnancy?

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Smoking during pregnancy is Photo by morgueFile.com

linked with a range of poor birth

outcomes—including:
58,59
Low birth weight and preterm birth
60
Restricted head growth
61
Placental problems
62
Increased risk of still birth
62,63
Increased risk of miscarriage

Health and developmental consequences among children have also been linked to prenatal smoke
exposure, including:
64
Poorer lung function, persistent wheezing, and asthma, possibly through DNA methylation
65
Visual difficulties, such as strabismus, refractive errors, and retinopathy

Unfortunately, smoking by pregnant women is common. In 2014, 8.4 percent of women smoked at any
time during pregnancy, with those aged 20 to 24 who were American Indian or Alaska Natives having
66
higher rates, at 13 percent and 18 percent, respectively. One fifth of women who smoked during the
first 6 months of pregnancy quit by their third trimester. Overall cessation rates were highest for those
with the highest educational attainment and private insurance.66 Therefore, there is a clear need to
expand smoking cessation treatment to younger women and to those of lower socioeconomic status
(see Box: "Smoking Cessation for Pregnant Women").

How many adolescents use tobacco?

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Most people who use tobacco Photo by NIDA

started during adolescence, and

those who begin at a younger
67
age are more likely to develop nicotine dependence and have trouble quitting. According to the 2017
Monitoring the Future Survey, 9.7 percent of 12th graders, 5.0 percent of 10th graders, and 1.9
12
percent of 8th graders used cigarettes in the past month. Analyses of the 2012 National Youth
Tobacco Survey (NYTS) found that 20.8 percent of current adolescent tobacco users reported wanting
to use tobacco within 30 minutes of waking—a classic symptom of nicotine dependence. This study
68
also found that 41.9 percent reported strong cravings for tobacco. Other research has found that
light and intermittent smoking among adolescents is associated with the same level of difficulty quitting
69
as daily smoking.

Any exposure to nicotine among youth is a concern. The adolescent brain is still developing, and
nicotine has effects on the brain’s reward system and brain regions involved in emotional and
70
cognitive functions. Research suggests that the nicotine-related changes to these areas of the brain
71
during adolescence may perpetuate continued tobacco use into adulthood. These changes also
contribute to a higher rate of other substance use disorders among people who use tobacco during
70,72
adolescence, sometimes referred to as a "gateway" effect.

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Mental health, beliefs about Photo by Mandie Mills, CDC

smoking, perception of
schoolmates’ smoking, and other
substance use are additional factors that can influence an adolescent’s risk for smoking and nicotine
73 74 75
dependence. Emotional problems—including depression and recent negative life events —are
associated with tobacco use among adolescents. Smoking among peers and within social groups is a
major environmental factor that influences adolescent smoking; social smoking is a more important
76
motivator for adolescents compared to adult smokers.

It is common for adolescent smoking to follow an intergenerational pattern, which has genetic,
73,77
epigenetic, and environmental influences. Data from parents and adolescents suggests that
current parental nicotine dependence is strongly linked with adolescent smoking and dependence.
Other factors—such as parents’ education, marital status, and parenting behavior also influence teen
smoking.

What are electronic cigarettes?

E-cigarettes (electronic nicotine delivery systems) emerged in the U.S. market in 2007 and have
78
rapidly grown in popularity. E-cigarettes, or e-vaporizers, are devices that heat a liquid containing
79
solvents, flavors, and often nicotine. Users inhale the resulting vapor. A variety of designs are
available, some mimicking the look of traditional cigarettes. More than 7,000 flavors are available for
80
e-cigarettes, some of which are especially appealing to youth. Many convenience stores, drug
stores, grocery stores, and other physical and online retail outlets sell e-cigarettes, although as of mid
December, 2019, it is illegal to sell any nicotine or tobacco products to people under 21.237 Some
convenience stores and drugstore chains have also stopped selling e-cigarettes to promote public
health.
78
In 2013, more than one third of cigarette smokers said they had ever used e-cigarettes. According to
data from the 2014 Tobacco Products and Risk Perceptions Survey, current cigarette smokers had a
greater likelihood of using e-cigarettes. This analysis found that half of cigarette smokers had ever
used an e-cigarette and 20.7 percent currently used these devices. However, approximately 10
81
percent of adults who used e-cigarettes had never smoked previously. Data from the 2014 National

Page 11
Health Interview Survey indicated that 0.4 percent of adults who have never smoked and 0.8 percent
of former smokers (abstinent 4 or more years) currently use e-cigarettes.82 The survey also found that
82
13 percent of daily e-cigarette users were former smokers who quit during the past year.

As with cigarette use, e-cigarette use is higher among people with mental health conditions—with 3.1
83
percent currently using compared with 1.1 percent of those without mental illness. It is also a
concern that pregnant women are using e-cigarettes, as nicotine exposure during periods of
84
developmental vulnerability (including prenatal development) has adverse health consequences.
85
Users report the belief that e-cigarette products are less harmful than traditional cigarettes, and
many report using them to help quit smoking traditional cigarettes. While it is not yet clear if e-
cigarettes are effective smoking cessation aids, the devices are sometimes marketed for this purpose
86
(see "Are e-cigarettes useful for smoking cessation?"). Some research suggests that older adults
use these devices as a tobacco substitute, although not always as a cessation method.87 Users also
88
cite convenience and being conscientious towards others as reasons for using these products.

Reports of Deaths Related to Vaping

The Food and Drug Administration has alerted the public to thousands of reports of serious lung
illnesses associated with vaping, including dozens of deaths. They are working with the Centers
for Disease Control and Prevention (CDC) to investigate the cause of these illnesses. Many of the
suspect products tested by the states or federal health officials have been identified as vaping
products containing THC, the main psychotropic ingredient in marijuana. Some of the patients
reported a mixture of THC and nicotine, and some reported vaping nicotine alone. No one
substance has been identified in all of the samples tested, and it is unclear if the illnesses are
related to one single compound. Until more details are known, FDA officials have warned people
not to use any vaping products bought on the street, and they warn against modifying any
products purchased in stores. They are also asking people and health professionals to report any
adverse effects. The CDC has posted an information page for consumers.

The Food and Drug Administration has alerted the public to thousands of reports of serious lung
illnesses associated with vaping, including dozens of deaths. They are working with the Centers

Page 12
for Disease Control and Prevention (CDC) to investigate the cause of these illnesses. Many of the
suspect products tested by the states or federal health officials have been identified as vaping
products containing THC, the main psychotropic ingredient in marijuana. Some of the patients
reported a mixture of THC and nicotine; and some reported vaping nicotine alone. While the CDC
and FDA continue to investigate possible other contributing substances, CDC has identified a
thickening agent—Vitamin E acetate—as a chemical of concern among people with e-cigarette or
vaping associated lung injuries. They recommend that people should not use any product
containing Vitamin E acetate, or any vaping products containing THC; particularly from informal
sources like friends, family, or in-person and online dealers. They also warn against modifying
any products purchased in stores, or using any vaping products bought on the street. People,
including health professionals, should report any adverse effects of vaping products. The CDC
has posted an information page for consumers.

How does the federal government regulate e-cigarettes?

The U.S. Food and Drug Administration (FDA), which regulates cigarettes, tobacco, and
smokeless tobacco, gained the authority in 2016 to also regulate electronic nicotine delivery
systems (such as e-cigarettes and vape pens), all cigars, hookah (waterpipe) tobacco, pipe
tobacco, and nicotine gels, among other tobacco products. Under the new regulations, e-cigarette
manufacturers must list ingredients. In December 2019, the federal government raised the legal
minimum age of sale of tobacco products from 18 to 21 years, and in January 2020, the FDA
issued a policy on the sale of flavored vaping cartridges

Is it true that e-cigarettes are safer than traditional cigarettes?

It is likely that, on balance, e-cigarettes are safer than traditional cigarettes from the
standpoint of physical health. However, as discussed above, the nicotine in e-cigarettes can
cause addiction and neurocognitive impairments.

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Although for regulatory purposes e-cigarettes are classified as “tobacco products,” they do
not contain tobacco or produce the same toxic combustion products, like tar, that cause
lung cancer and other diseases in users and people exposed to secondhand smoke.
However, the vapor from e-cigarettes typically contains nicotine and a range of other
89
chemicals. Because these products are relatively new, evidence on the short-term effects
of exposure to e-cigarette aerosols is limited, and very little is known about the long-term
health effects.

A review of recent literature found that some of the chemicals in e-cigarette liquid,
89
propylene glycol and glycerol, cause throat irritation and coughing. Other research
89
suggests that vapor exposure may be linked with impaired lung function. Chemical
analyses that compare the profiles of electronic and traditional cigarettes have suggested
that e-cigarettes have a reduced carcinogenic profile and impart a lower potential for
90
disease. However, toxicants, carcinogens, and metal particles have been detected in the
liquids and aerosols of e-cigarettes, and it is currently unclear what risk they pose with
91
repeated use. As with traditional cigarettes, use of e-cigarettes involuntarily exposes
91
nonusers to secondhand and thirdhand aerosol.

The research on secondhand exposure to the aerosol from e-cigarettes is limited, but one
study found that fine particulate matter concentrations during an indoor event in a large
room with e-cigarette smokers were higher than those reported previously in venues that
88
allowed cigarette smoking. An in vitro study showed that exposing lung tissues and cells
to e-cigarette liquid induced increased inflammatory responses and oxidative stress
92
markers. Another study that analyzed e-cigarette flavorings found that 39 of the 51 flavors
tested positive for diacetyl, a chemical associated with an irreversible obstructive lung
disease called bronchiolitis obliterans. Other chemicals, 2,3-pentanedione and acetoin,
associated with severe respiratory diseases among exposed people, were also found in
89
many e-cigarette flavorings.

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 The amount of nicotine in e-cigarette fluid varies. Some research has found that e-
cigarettes deliver less nicotine on average than traditional cigarettes,93 but that users may
change puffing patterns to compensate. Inexperienced e-cigarette users take in modest
nicotine concentrations, but those who regularly use these devices adjust their puffing to
consume similar levels of the drug as with traditional cigarettes.93–95 Newer e-cigarette
devices can deliver substantial amounts of nicotine, and some users are able to get nicotine
96 97,98
at levels similar to or even greater than a traditional cigarette. One study found
equivalent levels of nicotine's major metabolite in the blood of smokers who use traditional
89
and e-cigarettes. Thus, all the nicotine-related concerns of traditional
cigarettes—addiction, effects on cognitive function, and effects on prenatal
development—apply to e-cigarettes as well.

Risks of E-Cigarettes to Children

Young children may accidentally ingest the concentrated nicotine (which often contains
91
flavors) in e-cigarette liquid. The Centers for Disease Control and Prevention recently
compared calls to poison centers in the United States related to human exposures to
e-cigarettes and traditional cigarettes. The study found that between September 2010
and February 2014, the proportion of e-cigarette calls among all cigarette-related calls
99
increased from 0.3 percent to 41.7 percent. Most of the e-cigarette exposures were
among children under the age of 5 years (51.1 percent) and people over age 20 (42.0
percent), whereas almost all traditional cigarette exposure calls involved young
99
children. Data indicated that a greater proportion of e-cigarette exposure calls (57.8
percent) resulted in adverse health effects than traditional cigarette exposure (36.0
99
percent). These adverse health effects included vomiting, nausea, and eye irritation.

Are e-cigarettes useful for smoking cessation?

Some research suggests e-cigarettes may help people quit smoking cigarettes, while other
data suggest that they can impede quitting and that they may open the door to traditional
cigarette use for people who might not otherwise try them. Thus, much more research is

Page 15
 needed on this question.

One review of recent studies suggested that the likelihood of quitting cigarettes was 28
percent lower among individuals who used e-cigarettes compared with those who did not
100
use these devices, regardless of whether users were interested in quitting. Research
from the United Kingdom suggests that among smokers who continue to use traditional
cigarettes, daily use of e-cigarettes was associated with increased attempts to quit and cut
101
back, but not with success. However, another analysis estimated that, in England, 16,000
smokers were able to quit in 2014 who would not have quit if e-cigarettes had not been
102
available. A review and meta-analysis also suggested that using e-cigarettes for a
minimum of 6 months was associated with quitting or reducing the number of cigarettes
103
used.
E-cigarettes and Teens
National survey data suggest that e-cigarettes were the most commonly used nicotine
12–17
delivery product among youth. A review of the literature found that up to 20 percent of
87
adolescents who currently use e-cigarettes had never smoked a traditional cigarette.

A major concern is that e-cigarettes’ flavors, design, and marketing particularly appeal to
91
youth, and that by introducing young people to nicotine and glamorizing a smoking-like
behavior, e-cigarettes could open the door to cigarette use in a population that is particularly
vulnerable to addiction and that has seen historic declines in cigarette smoking.

Some research indicates that e-cigarette use may lead to the use of traditional cigarettes
104
among adolescents and young adults. According to data from the 2012 NYTS, youth who
had only used e-cigarettes reported an increased intention to smoke traditional cigarettes
compared with peers who had never used these devices. The survey found no link between
e-cigarette use and intention to quit smoking among youth who were current smokers,
indicating that this age group does not see these products primarily as smoking-cessation
105
aids. A longitudinal cohort study of 16- to 26-year-olds who had never smoked traditional
cigarettes found that 2.3 percent (16 participants) used e-cigarettes at the start of the study.
After a one-year follow-up, approximately 69 percent (11 of 16) of these participants

Page 16
 progressed to smoking traditional cigarettes compared to 18.9 percent (128 of 678) among
those who never used an e-cigarette.106 Another study found that past-month e-cigarette
use predicted future cigarette use, but that past-month cigarette use did not predict future e-
107
cigarette use.

Many young people report experimenting with e-cigarettes out of curiosity, because the
108
flavors appeal to them, or because of peer influences. The majority of youth who reported
e-cigarette use in one study had friends who used these products. Almost half of
adolescents who used e-cigarettes said that they did not believe these products were
109
associated with health risks. Young people also perceived e-cigarettes as easy to obtain,
"cool," and a better alternative to cigarettes because they were thought to be healthier and
could be used anywhere. Among youth who stopped using e-cigarettes, the major
underlying reasons were health concerns, loss of interest, high cost, bad taste, and view of
108
e-cigarettes as less satisfying than cigarettes.

Other Tobacco Products

While cigarette smoking has declined significantly during the past 40 years, use of other tobacco
110
products is increasing—particularly among young people. These include:

Cigars: tobacco wrapped in leaf tobacco or another tobacco-containing substance instead of

paper, which can be bought individually
Cigarillos: small cigars that cost less and are also available for purchase individually
Hookahs or waterpipes: pipes with a long, flexible tube for drawing smoke from lit, flavored
tobacco through water contained in a bowl
Smokeless tobacco: products like chewing tobacco and snuff that are placed in the mouth
between the teeth and gums
Powder tobacco: mixtures that are inhaled through the nose

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In 2014, almost one-quarter of high school students reported past-month use of a tobacco
product—with e-cigarettes (13.4 percent), hookahs (9.4 percent), cigarettes (9.2 percent), cigars (8.2
percent), smokeless tobacco (5.5 percent), and snus (moist powder tobacco) (1.9 percent) as the most
17
popular.

Cigars
In 2016, an estimated 12 million people aged 12 or older (4.6 percent of the adolescent and adult
7
population) smoked cigars during the past month. The majority of adolescents and young adults who
111
smoked cigars also smoke cigarettes.

Cigarillos
Data from the Tobacco Use Supplement to the Current Population Survey and NSDUH suggest that
111
younger and less economically advantaged males initiate tobacco use with cigarillos. From 2002 to
2011, past-month cigarette smoking declined for males and females of all age groups. However,
during this same period, rates of cigarillo use among males aged 18 to 25 remained constant (at
111
approximately 9 percent).

Hookahs or waterpipes
Between 2011 and 2014, use of hookah increased among middle and high school students, despite
17
decreased use of cigarettes and cigars, according to the NYTS. Research also suggests that rates of
112
hookah use for tobacco smoking increase during the first month of college. Nationally
representative data from college students indicate that daily cigarette or cigar smokers (as well as
113
marijuana users) were more likely to be frequent waterpipe users.

Hookah users may mistakenly believe that it is less addictive or dangerous than cigarettes; however,
one session of hookah smoking exposed users to greater smoke volumes and higher levels of tobacco
114
toxicants (e.g., tar) than a single cigarette. Additionally, hookah smoking is linked with nicotine
115,116
dependence and its associated medical consequences (see "What are the physical health
consequences of tobacco use?"). Reviews of the literature on waterpipe users suggest that like those
115
who use other forms of tobacco, many have tried to quit but have been unsuccessful on their own.
These findings indicate the need for tobacco control policies and prevention and treatment
interventions for this form of nicotine delivery that are similar to those seen for cigarettes.

Page 18
Smokeless tobacco
In 2016, 8.8 million people aged 12 or older (3.3 percent of this population) used smokeless tobacco
7
during the past month. Overall, use of smokeless tobacco among adults decreased from 1992 to
117
2003 but has held constant since. Longitudinal data suggest that people are more likely to switch
118
from smokeless tobacco use to cigarette smoking than vice versa. Although smokers may attempt
116
to use smokeless products to cut down or quit, research suggests that this approach is not effective.
However, some argue that using smokeless tobacco in lieu of cigarettes may help reduce the harms
119
associated with smoking traditional cigarettes.

Polytobacco Use
Some users of tobacco consume it in multiple forms (polytobacco use); this behavior is associated
72
with greater nicotine dependence120 and the risk for other substance use disorder. Analyses of a
decade of data from NSDUH found steady rates of polytobacco use from 2002 to 2011 (8.7 percent to
7.4 percent) among people age 12 and older. However, use of some product combinations—such as
cigarettes and smokeless tobacco, cigars and smokeless tobacco, and use of more than two
120
products—increased over that period.

Among individuals younger than 26, rates of polytobacco use increased despite declines in overall
tobacco use. Polytobacco use was associated with being male, having relatively low income and
120
education, and engaging in risk-taking behaviors. In 2014, an estimated 2.2 million middle and high
school students had used two or more types of tobacco products during the past month, according to
121
the NYTS. Polytobacco use was common, even among students who used tobacco products 5 days
121
or fewer during the past month. The 2012 NYTS had found that 4.3 percent of students used three
or more types of tobacco. This study also observed that male gender, use of flavored products,
nicotine dependence, receptivity to tobacco marketing, and perceived peer use were all associated
122
with youth polytobacco use.

Flavored Tobacco Use Among Adolescents and Young Adults

One specific concern about e-cigarettes and tobacco products like cigarillos and hookahs is the
17,111
addition of flavorings, which may make them particularly appealing to youth. The Family

Page 19
 Smoking Prevention and Tobacco Control Act of 2009 banned the sale of cigarettes with flavors
other than menthol, but other flavored tobacco products (e.g., small cigars, cigarillos, and
smokeless tobacco) can still be sold. Adding flavors to tobacco products or to the nicotine
solution of e-cigarettes can make them more appealing to some users because they can mask
108,123
the harsh taste. Although more research is needed on how flavors affect long-term use,
health experts have expressed concerns that many of the flavorings used in tobacco products are
124
also found in candies and beverages. Such flavors may make them more appealing to youth
and may contribute to increased use of these products among young people.

Approximately 6.3 percent of middle and high school students reported using either flavored
125
cigarettes or small cigars, according to the 2011 NYTS. Data from the 2014 NYTS indicate that
of middle and high school students who currently used tobacco, about 70 percent—an estimated
126
3.26 million youths—had used at least one flavored tobacco product during the past month.
Among past-month users, the most commonly used flavored products were e-cigarettes, hookah
126
tobacco, and cigars. It seems that youth may not necessarily “grow out of” using flavored
tobacco products. Among young adults aged 18 to 34, nearly one-fifth (18.5 percent) of those
127
who use tobacco, consumed flavored (including menthol) products.

Are there gender differences in tobacco smoking?

Page 20
Generally, men tend to use all Photo by ©Thinkstock.com/BananaStock

tobacco products at higher rates

128
than women. In 2015, 16.7
129
percent of adult males and 13.6 percent of adult females smoked cigarettes. Such differences may
relate to a combination of physiological (particularly ovarian hormones), cultural, and behavioral
130
factors.

Results from neuroimaging studies suggest that smoking activates men’s reward pathways more than
131
women's. This finding is consistent with the idea that men smoke for the reinforcing effects of
nicotine, whereas women smoke to regulate mood or in response to cigarette-related cues. A study of
stress responses and craving among male and female smokers who were trying to quit found that
during abstinence, lower levels of the stress hormone cortisol predicted relapse in men. However, high
132
cortisol levels were predictive of relapse in women. Other work on abstinence found that smoking a
cigarette with nicotine, as compared to a de-nicotinized cigarette, alleviated the symptoms of
withdrawal and negative mood to a greater extent in men than women. Women obtained equal relief
from cigarettes with and without nicotine, suggesting that they found the drug less rewarding than
133
men.

Cigarette craving is a major reason why smokers find it hard to quit, and this strong urge to smoke can
be evoked by sensory cues and stress. Research suggests that women experience stronger craving
134 135
than men in response to stress, but men may be more responsive to environmental cues.
Additionally, longitudinal data from international surveys conducted in four industrialized countries
indicated that men and women did not differ in their desire to quit, plans to quit, or quit attempts.
136
However, women were 31 percent less likely to quit successfully. One reason why women may
have difficulty quitting is post-cessation weight gain. This concern should be addressed in behavioral
137
counseling and adjunct treatments for all smokers.

The overall lower cessation rate for women may reflect sex differences in response to particular
medications (see "What are treatments for tobacco dependence?"). For example, varenicline has
greater short- and immediate-term efficacy (at 3 and 6 months) among women smokers. However,
138
women and men show similar 1-year quit rates when using varenicline. In contrast, a combination of
139
varenicline plus bupropion was less effective for cessation among women compared with men.

Page 21
Another particular concern related to tobacco use among women is smoking during pregnancy (see "
What are the risks of smoking during pregnancy?").

Do people with mental illness and substance use disorders

use tobacco more often?
A larger proportion of people diagnosed with mental disorders report cigarette smoking compared with
people without mental disorders. Among US adults in 2019, the percentage who reported past-month
cigarette smoking was 1.8 times higher for those with any past-year mental illness than those without
140
(28.2% vs. 15.8%). Smoking rates are particularly high among people with serious mental illness
(those who demonstrate greater functional impairment). While estimates vary, as many as 70-85% of
141,142
people with schizophrenia and as many as 50-70% of people with bipolar disorder smoke.

Rates of smoking among people with mental illness were highest for young adults less than age 45,
143
those with low levels of education, and those living below the poverty level. The 2005-2013 National
Survey on Drug Use and Health (NSDUH) data indicated that smoking among adults without chronic
conditions has declined significantly, but remains higher among those reporting anxiety, depression,
3
and substance use disorders. Similarly, a recent study based on the 2006-2019 NSDUH data showed
higher smoking rates in adults with psychiatric disorders than in those without; however, most
importantly, smoking rates among adults with major depression and/or substance use disorder
declined significantly during 2006-2019 in every examined age, sex, and racial and ethnic subgroup,
except for non-Hispanic American Indian or Alaska Native adults. These results suggest that tobacco
238
cessation is achievable among adults with psychiatric disorders and tobacco use.

Smoking is believed to be more prevalent among people with depression and schizophrenia because
nicotine may temporarily lessen the symptoms of these illnesses, such as poor concentration, low
144–146
mood, and stress. But it is important to note that smoking cessation has been linked with
improved mental health—including reduced depression, anxiety, and stress, and enhanced mood and
147
quality of life.

In addition to smoking, there is also a higher prevalence of smokeless tobacco use among individuals
3
with anxiety or substance use disorders. Other research drawing on data from the National

Page 22
Epidemiologic Survey on Alcohol and Related Conditions (NESARC) found that all types of substance
148
dependence were associated with dependence on nicotine. Smoking is also highly prevalent among
149
people in treatment for substance use disorders, with most studies finding rates between 65-85%
149
among people in addiction treatment.

Additionally, people who smoke with a mental health disorder tend to smoke more cigarettes than
those in the general population. The average number of cigarettes smoked during the past month was
higher among those with a mental illness compared with those without one—331 versus 310
150
cigarettes. High cigarette consumption is a particular problem for people with serious mental illness.
Although adults with both tobacco addiction and co-occurring mental disorders apart from substance
use disorders comprised only 7.1% of the total U.S. population, they consumed 34.2% of all cigarettes
151
smoked in the U.S., according to data from the 2001–2002 NESARC.

High Prevalence of Smoking Among People with Schizophrenia

Researchers are working to identify the brain circuits that contribute to the high prevalence of smoking
among people with schizophrenia. Schizophrenia is associated with widespread reductions in
functional connectivity between the dorsal anterior cingulate cortex and diverse parts of the limbic
system. One report identified 15 circuits for which the reduction of functional connectivity correlated
152
with severity of nicotine addiction.

People with substance use disorders and other mental illnesses, do not quit smoking at the same rate
4
as those in the general population. Survey responses from people who have smoked at some point
during their lives indicated that fewer smokers with mental illness had quit compared to those without
psychiatric disorders: 47.4% of lifetime smokers without mental illness smoked during the past month,
150
compared with 66% of those with mental illness. A recent study found that among U.S. adults in
2019, the percentage who reported past-month cigarette smoking was higher among those with past-
year major depressive episodes than those without (24.2% vs. 17.6%) and among those with past-
238
year substance (alcohol or drug) use disorders than those without (35.8% vs. 16.8%).

Having a mental disorder at the time of cessation is a risk factor for relapse to smoking, even for those
153
who have sustained abstinence for more than a year. Many smokers with mental illness want to quit
for the same reasons cited by others (such as health and family), but they may be more vulnerable to
154
relapse related to stress and other negative feelings.

Page 23
The disparity in smoking prevalence is costing lives. A recent study found that tobacco-related
diseases accounted for approximately 53% of deaths among people with schizophrenia, 48% among
155
those with bipolar disorder, and 50% among those with depression.

Since the 1980s, many providers have believed that people with schizophrenia smoke to obtain relief
147
from symptoms like poor concentration, low mood, and stress. But research is now showing that
smoking is associated with worse behavioral and physical health outcomes in people with mental
147,156
illness, and quitting smoking is showing clear benefits for this population. Comprehensive
tobacco control programs and enhanced efforts to prevent and treat nicotine addiction among those
with mental illness would reduce illness and deaths. Integrated treatment—concurrent therapy for
157
mental illness and nicotine addiction—will likely have the best outcomes.
6
Smokers who receive mental health treatment have higher quit rates than those who do not.
Moreover, evidence-based treatments that work in the general population are also effective for people
with mental illness. For example, people with schizophrenia showed better quit rates with the
medication bupropion, compared with placebo, and showed no worsening of psychiatric symptoms.
158,159
A combination of the medication varenicline and behavioral support has shown promise for
helping people with bipolar and major depressive disorders quit, with no worsening of psychiatric
160
symptoms. A clinical trial found that a combination of varenicline and cognitive behavioral therapy
(CBT) was more effective than CBT alone for helping people with serious mental illness stop smoking
161
for a prolonged period—after 1 year of treatment and at 6 months after treatment ended.

What are treatments for tobacco dependence?

Page 24
There are effective treatments Photo by ©iStock

that support tobacco cessation,

including both behavioral
therapies and FDA-approved medications. FDA-approved pharmacotherapies include various forms of
nicotine replacement therapy as well as bupropion and varenicline. Research indicates that smokers
who receive a combination of behavioral treatment and cessation medications quit at higher rates than
37,40,162–167
those who receive minimal intervention. Interventions such as brief advice from a health
care worker, telephone helplines, automated text messaging, and printed self-help materials can also
163
facilitate smoking cessation. Cessation interventions utilizing mobile devices and social media also
168
show promise in boosting tobacco cessation. It is important for cessation treatment to be as
personalized as possible, as some people smoke to avoid negative effects of withdrawal while others
are more driven by the rewarding aspects of smoking.

Surgeon General’s Report on Smoking Cessation

The Surgeon General’s Report on Smoking Cessation, released in January 2020, offers evidence
that smoking cessation is beneficial at any age, improves health status and enhances quality of
life. It also reduces the risk of premature death and can add as much as a decade to life
expectancy.

The prevalence of tobacco use and dependence among adolescents—as well as the neurobiological
impact and medical consequences of nicotine exposure—suggest that pediatric primary care settings
169
should deliver tobacco cessation treatments to both youth and parents who use tobacco. Current
clinical guidance does not recommend medications for adolescent tobacco cessation because of a
170
lack of high-quality studies; however, a combination of behavioral treatments—such as motivational
171
enhancement and CBT—has shown promise for helping adolescents quit tobacco. More well-
designed smoking cessation studies need to be conducted with adolescent smokers, particularly in the
170
area of pharmacologic treatments for nicotine dependence.

Behavioral Treatments

Page 25
Behavioral counseling is typically provided by specialists in smoking cessation for four to eight
40
sessions. Both in-person and telephone counseling have been found beneficial for patients who are
164
also using cessation medications. A variety of approaches to smoking cessation counseling are
available.

Cognitive Behavioral Therapy (CBT)—CBT helps patients identify triggers—the people, places, and
things that spur behavior—and teaches them relapse-prevention skills (e.g., relaxation techniques)
172,173
and effective coping strategies to avoid smoking in the face of stressful situations and triggers. A
study that compared CBT and basic health education observed that both interventions reduced
174
nicotine dependence. However, another study found that among smokers trying to quit with the
nicotine replacement therapy (NRT) patch, patients who participated in six sessions of intensive group
175
CBT had better quit rates than those who received six sessions of general health education.

Motivational Interviewing (MI)—In MI, counselors help patients explore and resolve their
ambivalence about quitting smoking and enhance their motivation to make healthy changes. MI is
patient-focused and nonconfrontational, and providers point out discrepancies between patients’ goals
or values and their current behaviors. They adjust to patients’ resistance to change and support self-
173
efficacy and optimism. Studies of MI suggest that this intervention results in higher quit rates than
176
brief advice to stop smoking or usual care.

Mindfulness—In mindfulness-based smoking cessation treatments, patients learn to increase

177
awareness of and detachment from sensations, thoughts, and cravings that may lead to relapse. In
this therapy, patients purposely attend to the thoughts that trigger cravings and urges for tobacco and
cognitively reframe them as expected and tolerable. Patients learn techniques that help them tolerate
negative emotions—including stress and cravings—without returning to tobacco use or other
177
unhealthy behaviors. Interest in mindfulness-based treatments has increased during the past
decade, and studies show that this approach benefits overall mental health and can help prevent
178
relapse to smoking. However, well-controlled clinical trials are needed.

Telephone support and quitlines—As part of tobacco control efforts, all states offer toll-free
telephone numbers (or quitlines) with smoking cessation counselors who provide information and
support (800-QUIT-NOW or 800-784-8669). Studies of quitline interventions indicate that smokers who
179
call quitlines benefit from these services, particularly when a counselor calls them back for multiple

Page 26
 180
sessions. There is limited evidence on the optimal number of calls needed, but smokers who
participated in three or more calls had a greater likelihood of quitting, compared with those who only
180
received educational materials, brief advice, or pharmacotherapy alone. Quitlines have also been
181
shown to help smokeless tobacco cessation. The U.S. Department of Health and Human Services
provides a Smoking Quitline (877-44U-QUIT or 877-448-7848), as well as more information and tools
for quitting (including text messages and other telephone-based support) at https://smokefree.gov/.

Text messaging, web-based services, and social media support—Technology, including mobile
phones, internet, and social media platforms can be used to provide smoking cessation interventions.
These technologies have the power to increase access to care by extending the work of counselors
and overcoming the geographical barriers that may deter people from entering treatment.

A review of the literature on technology-based smoking cessation interventions (internet, personal

computer, and mobile telephone) found that these supports can increase the likelihood of adults
quitting, compared with no intervention or self-help information, and they can be a cost-effective
182
adjunct to other treatments. A technology does not necessarily have to be recent or highly
sophisticated to help boost cessation rates. For example, studies suggest that adults who receive
encouragement, advice, and quitting tips via text-message—a capability on even the most basic
183,184
mobile devices—show improved quit rates compared with control programs.

Among adult tobacco users who called a state quitline, most selected an integrated phone/web
185
cessation program in favor of a web-only intervention. Participants who chose the web-only option
tended to be younger and healthier smokers, with a higher socioeconomic status. These participants
tended to interact intensely with the site once, but did not re-engage as much as those who opted for
the phone/web combination. A review of internet-based smoking cessation programs for adults
suggested that interactive internet-based interventions that are tailored to individual needs can help
186,187
people quit for 6 months or longer. Future research should determine the effectiveness of
different technologies for smoking cessation support among populations that may be hard to reach,
including those of low socioeconomic status and adults older than age 50.

Technology-based cessation interventions are particularly relevant to young adults aged 18 to

7
25—about 3.2 million of whom smoked daily in 2016. A systematic review and meta-analysis of
published randomized trials of technology-based interventions—including computer programs,

Page 27
internet, telephone, and text messaging—for smoking cessation among this population found that they
188
increased abstinence by 1.5 times that of comparison subjects. Researchers recommend
189
embedding cessation interventions in commonly used social networking platforms, and there has
been some exploratory work in this area. Results of a trial with a relatively small number of participants
suggested that Facebook was an accessible, low-cost platform for engaging young adults considering
cessation. However, the study pointed to challenges in maintaining participation, retaining young
189
people in the program, and the need for gender-specific features. A randomized controlled trial has
been designed to test a stage-based smoking cessation intervention on Facebook tailored for smokers
aged 18 to 25. Participants will be recruited online, randomly assigned to a Facebook group according
to their readiness to quit, and will receive tailored daily messages and weekly counseling. The study
will assess the intervention’s impact on abstinence from smoking 3, 6, and 12 months after treatment,
number of cigarettes smoked, quit attempts lasting 24 hours or more, and commitment to abstinence.
190

Smoking Cessation for Pregnant Women

Given the risks associated with smoking during pregnancy, but also the challenges faced by all
smokers when trying to quit, researchers have studied an array of approaches to improve
cessation rates for this population. Many women are motivated to quit during pregnancy, but like
other smokers, most will need assistance.

Studies show that behavioral treatments are effective, whereas pharmacotherapies have only
191
marginal success. A combination of incentives and behavioral counseling is most effective for
192
pregnant women. Adding vouchers to routine care (which included free nicotine replacement
therapy for 10 weeks and four weekly support phone calls) more than doubled cessation rates
193
during pregnancy. Pooled results of behavioral intervention studies indicate that treatment
reduced preterm births and the proportion of infants born with low birth weight, compared with
194
usual care. This finding is supported by an analysis of pooled results from studies with
economically disadvantaged pregnant smokers, which found that voucher-based incentives
improved sonographically estimated fetal growth, birth weight, percentage of low-birth-weight
195,196
deliveries, and breastfeeding duration.

Page 28
Medications
Nicotine Replacement Therapy
(NRT)—A variety of formulations
of nicotine NRTs are available
over the counter—including the
transdermal patch, spray, gum,
and lozenges—and are equally
37,38,197,198
effective for cessation.
NRTs stimulate the brain receptors targeted by nicotine, helping relieve nicotine withdrawal symptoms
37
and cravings that lead to relapse. Many people use NRT to help them get through the early stages of
cessation, and those with more severe nicotine addiction can benefit from longer-term treatment. Use
of NRT improves smoking cessation outcomes, and adding behavioral therapies further increases quit
198
rates. A combination of continual nicotine delivery through the transdermal patch and one other
form of nicotine taken as needed (e.g., lozenge, gum, nasal spray, inhaler) has been found to be more
37,167,198
effective at relieving withdrawal symptoms and cravings than a single type of NRT.
37
Researchers estimate that NRT increases quit rates by 50 to 70 percent. Using the patch for up to
39
24 weeks has been shown to be safe.

Bupropion—Bupropion (immediate-release and extended-release) was originally approved as an

antidepressant. It works by inhibiting the reuptake of the brain chemicals norepinephrine and
dopamine as well as stimulating their release. Bupropion has been found to increase quit rates
166,198,199
compared with placebo in both short- and long-term follow-up studies and is indicated for
167
smoking cessation. It is equally effective to NRT.

Varenicline—Varenicline helps reduce nicotine cravings by stimulating the alpha-4 beta-2 nicotinic
receptor but to a lesser degree than nicotine. Varenicline boosts the odds of successfully quitting,
198
compared with unassisted attempts. Varenicline increased the likelihood of quitting compared with
200,201
placebo, and some studies find that it is more effective than single forms of NRT and bupropion.
167 Photo by ©istock.com/HconQ
In a primary care setting, 44 percent of patients on varenicline, either alone or combined with
counseling, were abstinent at the 2-year follow-up. Patients who participated in group therapy and
202
adhered to the medication were more likely to remain abstinent. Research also suggests that this
199
medication may be more effective than bupropion.

Page 29
Medication combinations—Some studies suggest that combining NRT with other medications may
facilitate cessation. For example, a meta-analysis found that a combination of varenicline and NRT
203
(especially, providing a nicotine patch prior to cessation) was more effective than varenicline alone.
199
Similarly, adding bupropion to NRT also improved cessation rates. For smokers who could not cut
down significantly by using the NRT patch, combining extended-release bupropion and varenicline
was more effective than placebo, particularly for men and those who were severely nicotine
139
dependent.

Other antidepressants—In addition to bupropion, some other antidepressant medications have also
been found effective for smoking cessation, independent of their antidepressant effects, and are
considered second-line treatments. A few small studies suggest that nortriptyline is equally effective as
167,199
NRT. Although nortriptyline may have side effects in some patients, the small studies for its use
199
in smoking cessation have not reported any. Researchers have not observed any impact of
selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, paroxetine, and sertraline) on
199
smoking, either alone or in combination with NRT.

Precision Medicine—Researchers have been examining ways to personalize treatment based on

important individual biological differences, including genetic differences. The field of pharmacogenetics
examines how genes influence therapeutic response to medications, providing critical information to
help tailor pharmacotherapies to the individual for maximum benefit. For example, people metabolize
nicotine at different rates because of variations in several genes. Individuals who metabolize nicotine
204
quickly smoke more, show greater dependence, and have more difficulty quitting. Such genetic
204,205
variation influences the therapeutic responses to NRT and other cessation medications. A recent
study compared rates of abstinence 1 week after treatment for slow, normal, and fast metabolizers of
nicotine who were randomly assigned to either placebo, NRT, or varenicline. Results indicated that
varenicline worked best for normal nicotine metabolizers, whereas NRT patches were most effective
205,206
for slow metabolizers.

Promising medications and ongoing research—NIDA supports research to develop new and
improve current treatment options for smoking cessation based on a growing understanding of the
neurobiology of addiction. In the area of medications, research is focusing on the receptors targeted
208
by nicotine and the brain circuits and regions known to influence nicotine consumption. Newer brain
targets—including the orexin and glutamate signaling systems—have also shown promise for

Page 30
 207,208
medication treatment. Repurposing medications already on the market for other indications may
209,210
also prove useful in the search for new smoking cessation therapies. This approach has been
successful in the past, as bupropion was an established antidepressant before the FDA approved it as
a smoking cessation medication. One current candidate is N-acetylcysteine, a medication for
acetaminophen overdose, which has shown promise as a treatment for various substance use
211
disorders—including nicotine dependence. Another approach that could prevent relapse and that
has shown promise in early studies is a nicotine vaccine, which would generate antibodies that keep
212,213
nicotine from reaching the brain.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a relatively new approach being tested to treat addiction. It
is a physiological intervention that noninvasively stimulates neural activity in targeted areas of the
brain using magnetic fields. Multiple TMS pulses given consecutively are referred to as repetitive TMS
(rTMS). The FDA has approved two rTMS devices for depression treatment in adults.

Research on rTMS as a treatment for smoking cessation is in early stages but has shown promise.
214,215
Among adult smokers who had not been able to quit using other treatments, high-frequency
TMS treatment significantly reduced the number of cigarettes smoked. Combining high-frequency
TMS with exposure to smoking cues improved effectiveness and boosted the overall abstinence rate
to 44 percent at the end of the treatment. Six months after treatment, 33 percent of participants
216
remained abstinent from cigarettes. Future randomized controlled clinical trials with large numbers
of patients will be needed to establish its efficacy for smoking cessation.

How can we prevent tobacco use?

Page 31
The medical consequences of Photo by ©Shutterstock/Kenishirotie

tobacco use—including
secondhand exposure—make
tobacco control and smoking prevention crucial parts of any public health strategy. Since the first
Surgeon General’s Report on Smoking and Health in 1964, states and communities have made efforts
to reduce initiation of smoking, decrease exposure to smoke, and increase cessation. Researchers
estimate that these tobacco control efforts are associated with averting an estimated 8 million
premature deaths and extending the average life expectancy of men by 2.3 years and of women by
18
1.6 years. But there is a long way yet to go: roughly 5.6 million adolescents under age 18 are
13
expected to die prematurely as a result of an illness related to smoking.

Prevention can take the form of policy-level measures, such as increased taxation of tobacco
products; stricter laws (and enforcement of laws) regulating who can purchase tobacco products; how
and where they can be purchased; where and when they can be used (i.e., smoke-free policies in
restaurants, bars, and other public places); and restrictions on advertising and mandatory health
warnings on packages. Over 100 studies have shown that higher taxes on cigarettes, for example,
217
produce significant reductions in smoking, especially among youth and lower-income individuals.
218
Smoke-free workplace laws and restrictions on advertising have also shown benefits.

Prevention can also take place at the school or community level. Merely educating potential smokers
218
about the health risks has not proven effective. Successful evidence-based interventions aim to
reduce or delay initiation of smoking, alcohol use, and illicit drug use, and otherwise improve outcomes
for children and teens by reducing or mitigating modifiable risk factors and bolstering protective
factors. Risk factors for smoking include having family members or peers who smoke, being in a lower
socioeconomic status, living in a neighborhood with high density of tobacco outlets, not participating in
219
team sports, being exposed to smoking in movies, and being sensation-seeking. Although older
teens are more likely to smoke than younger teens, the earlier a person starts smoking or using any
addictive substance, the more likely they are to develop an addiction. Males are also more likely to
take up smoking in adolescence than females.

Some evidence-based interventions show lasting effects on reducing smoking initiation. For instance,
communities utilizing the intervention-delivery system, Communities that Care (CTC) for students aged
10 to14 show sustained reduction in male cigarette initiation up to 9 years after the end of the
220
intervention.

Page 32
What research is being done on tobacco use?
New scientific developments can improve our understanding of nicotine addiction and spur the
development of better prevention and treatment strategies.

Genetics and Epigenetics

221
An estimated 50-75 percent of the risk for nicotine addiction is attributable to genetic factors. A
cluster of genes (CHRNA5-CHRNA3-CHRNB4) on chromosome 15 that encode the ?5, ?3, and ?4
221–223
protein subunits that make up the brain receptor for nicotine are particularly implicated in
nicotine dependence and smoking among people of European descent. Variation in the CHRNA5
224
gene influences the effectiveness of combination NRT, but not varenicline. Other research has
225
identified genes that influence nicotine metabolism and therefore, the number of cigarettes smoked,
204,205 226
responsiveness to medication, and chances of successfully quitting. For example, the
therapeutic response to varenicline is associated with variants for the CHRNB2, CHRNA5, and
CHRNA4 genes, while bupropion-related cessation is linked with variation in genes that affect nicotine
227
metabolism.

Smoking can also lead to persistent changes in gene expression (epigenetic changes), which may
228
contribute to associated medical consequences over the long term, even following cessation.
Epigenetic changes may serve as a potential biomarker for prenatal tobacco smoke exposure.
Researchers found tobacco-specific changes at 26 sites on the epigenome, and this pattern predicted
229
prenatal exposure with 81 percent accuracy. A large scale meta-analysis of data on epigenetic
changes associated with prenatal exposure to cigarette smoke also identified many epigenetic
230
changes that persisted into later childhood. More research is needed to understand the long-term
health impacts of these changes.

Neuroimaging
Cutting-edge neuroimaging technologies have identified brain changes associated with nicotine
dependence and smoking. Using functional magnetic resonance imaging (fMRI), scientists can
visualize smokers’ brains as they respond to cigarette-associated cues that can trigger craving and
231
relapse. Such research may lead to a biomarker for relapse risk and for monitoring treatment
29
progress, as well as point to regions of the brain involved in the development of nicotine addiction.

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A neuroimaging technology called default-mode or resting-state fMRI (rs-fMRI) reveals intrinsic brain
activity when people are alert but not performing a particular task. Using this technique, researchers
are examining the neurobiological profile associated with withdrawal and how nicotine impacts
232
cognition. Comparisons between smokers and nonsmokers suggest that chronic nicotine may
weaken connectivity within brain circuits involved in planning, paying attention, and behavioral
233
control—possibly contributing to difficulty with quitting. fMRI studies also reveal the impact of
smoking cessation medications on the brain—particularly how they modulate the activity of different
brain regions to alleviate withdrawal symptoms and reduce smoking. A review of these studies
suggested that NRT enhances cognition during withdrawal by modulating activity in default-network
234
regions, but may not affect neural circuits associated with nicotine addiction.

Some imaging techniques allow researchers to visualize neurotransmitters and their receptors, further
27
informing our understanding of nicotine addiction and its treatment. Using these techniques,
researchers have established that smoking increases the number of brain receptors for nicotine.
28
Individuals who show greater receptor upregulation are less likely to stop smoking. Combining
neuroimaging and genetics may yield particularly useful information for improving and tailoring
treatment. For example, nonsmoking adolescents with a particular variant in the CHRNA5-CHRNA3-
CHRNB4 gene cluster (which is associated with nicotine dependence and smoking) showed reduced
brain activity in response to reward in the striatum as well as the orbitofrontal and anterior cingulate
cortex. This finding suggests that genetics can influence how the brain processes rewards which may
235
influence vulnerability to nicotine dependence. Neuroimaging genetics also shows that other genes,
including ones that influence dopamine neurotransmission, influence reward sensitivity and risk for
236
addiction to nicotine.

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Where can I get further information about tobacco/nicotine?

NIDA's website includes:
Information on drugs of use and misuse and related health consequences
NIDA publications, news, and events
Resources for health care professionals, educators, and patients and families
Information on NIDA research studies and clinical trials

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 Funding information (including program announcements and deadlines)
International activities
Links to related websites (access to websites of many other organizations in the field)
Information in Spanish (en español)

NIDA websites and webpages

nida.nih.gov/publications/drugfacts/cigarettes-other-tobacco-products
nida.nih.gov/publications/drugfacts/electronic-cigarettes-e-cigarettes
researchstudies.drugabuse.gov
irp.drugabuse.gov

For physician information

NIDAMED: nida.nih.gov/nidamed

Other websites
Information on nicotine/tobacco abuse is also available through the following websites:

National Cancer Institute (NCI)

Centers for Disease Control and Prevention (CDC)
Substance Abuse and Mental Health Services Administration (SAMHSA)
Monitoring the Future
The Partnership for Drug-Free Kids

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