Editor’s note:
A new
study by Harvard School of Public Health shows that the tobacco companies have
increased additive nicotine in four major brands of cigarettes by 11 percent
between 1998 and 2005.
Among others, smoking and use of other tobacco products are responsible
for one third of more than 1 million cases of cancer in the
U.S., according
to the American Cancer Society.
Here we
cite a document titled Tobacco Addiction from the National Institute on Drug
Abuse for those who want to know more about the issue.
For more information about the news report on the study,
read
Big
Tobacco Boosting Nicotine in Cigarettes: Study.
Tobacco Addition
What is the extent and impact of tobacco use?
According to the 2004 National Survey on Drug Use and
Health, an estimated 70.3 million Americans age 12 or older reported current
use of tobacco—59.9 million (24.9 percent of the population) were current
cigarette smokers, 13.7 million (5.7 percent) smoked cigars, 1.8 million (0.8
percent) smoked pipes, and 7.2 million (3.0 percent) used smokeless tobacco,
confirming that tobacco is one of the most widely abused substances in the
United States1. While these numbers are still unacceptably high, they represent
a decrease of almost 50 percent since peak use in 19652.
NIDA’s 2005 Monitoring the Future Survey of 8th-, 10th-, and
12th-graders, 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 9 percent of 8th-graders, 15 percent of
10th-graders, and 23 percent of 12th-graders had used cigarettes in the 30 days
prior to the survey3. Despite cigarette use being at the lowest levels of the
survey since a peak in the mid-1990s, the past few years indicate a clear
slowing of this decline. And while perceived risk and disapproval of smoking
had been on the rise, recent years have shown the rate of change to be
dwindling. In fact, current use, perceived risk, and disapproval leveled off
among 8th-graders in 20053, suggesting that renewed efforts are needed to
ensure that teens understand the harmful consequences of smoking.
Moreover, the declining prevalence of cigarette smoking
among the general
U.S.
population is not reflected in patients with mental illnesses. For them, it
remains substantially higher, with the incidence of smoking in patients
suffering from post-traumatic stress disorder, bipolar disorder, major
depression, and other mental illness twofold to fourfold higher than the
general population, and smoking incidence among people with schizophrenia as
high as 90 percent4,5,6.
Tobacco use is the leading preventable cause of death in the
United States.
The impact of tobacco use in terms of morbidity and mortality costs to society
is staggering. Economically, more than $75 billion of total
U.S. healthcare
costs each year is attributable directly to smoking7. However, this cost is
well below the total cost to society because it does not include burn care from
smoking-related fires, perinatal care for low birth-weight 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 $82 billion per year, bringing a conservative
estimate of the economic burden of smoking to more than $150 billion per year7.
How does tobacco deliver its effects?
Tobacco PlantThere are more than 4,000 chemicals found in
the smoke of tobacco products. Of these, nicotine, first identified in the
early 1800s, is the primary reinforcing component of tobacco that acts on the
brain.
Cigarette smoking is the most popular method of using
tobacco; however, there has also been a recent increase in the sale and
consumption of smokeless tobacco products, such as snuff and chewing tobacco.
These smokeless products also contain nicotine, as well as many toxic
chemicals.
The cigarette is a very efficient and highly engineered
drugdelivery system. By inhaling tobacco smoke, the average smoker takes in 1
to 2 mg of nicotine per cigarette8. 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 1-1/2 packs (30 cigarettes) daily gets
300 “hits” of nicotine to the brain each day. In those who typically do not
inhale the smoke—such as cigar and pipe smokers and smokeless tobacco
users––nicotine is absorbed through the mucosal membranes and reaches peak
blood levels and the brain more slowly.
Immediately after exposure to nicotine, there is a “kick”
caused in part by the drug’s stimulation of the adrenal glands and resulting discharge
of epinephrine (adrenaline). The rush of adrenaline stimulates the body and
causes a sudden release of glucose, as well as an increase in blood pressure,
respiration, and heart rate9. Nicotine also suppresses insulin output from the
pancreas, which means that smokers are always slightly hyperglycemic (i.e.,
they have elevated blood sugar levels10). The calming effect of nicotine
reported by many users is usually associated with a decline in withdrawal
effects rather than direct effects of nicotine.
Is nicotine addictive?
Yes. Most smokers use tobacco regularly because they are
addicted to nicotine9. Addiction is characterized by compulsive drug seeking
and use, 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 year7. Unfortunately, only about 6 percent of people who try to quit are
successful for more than a month11.
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 smokers9. 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 inhalation9. However, the acute effects of nicotine dissipate in a
few minutes, 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,
cognitive and attentional 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 may subside within a few weeks12. For some people,
however, symptoms may persist for months.
While 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. While nicotine gum and patches may alleviate the pharmacological
aspects of withdrawal, cravings often persist. Other forms of nicotine
replacement, such as inhalers, attempt to address some of these other issues,
while behavioral therapies can help smokers identify environmental triggers of
withdrawal and craving so they can employ strategies to prevent or circumvent
these symptoms and urges.
Are there other
chemicals that may contribute to tobacco addiction?
Yes, research is showing that nicotine may not be the only
psychoactive ingredient in tobacco. 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 dopamine13. This
change is likely caused by some tobacco smoke ingredient other than nicotine,
since 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.
Recently, NIDA-funded researchers have shown in animals that
acetaldehyde, another chemical constituent of tobacco smoke, dramatically
increases the reinforcing properties of nicotine and may also contribute to
tobacco addiction14. The investigators further report that this effect is
age-related, with adolescent animals displaying far more sensitivity to this
reinforcing effect14, suggesting 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, cocaine, heroin, homicide, suicide, car accidents,
fire, and AIDS combined15. Since 1964, more than 12 million Americans have died
prematurely from smoking, and another 25 million
U.S. smokers alive today will most
likely die of a smoking-related illness7.
Cigarette smoking harms every organ in the body. It has been
conclusively linked to leukemia, cataracts, and pneumonia, and accounts for
about one-third of all cancer deaths14. 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 nonsmokers17. Foremost among the
cancers caused by tobacco use is lung cancer—cigarette smoking has been linked
to about 90 percent of all lung cancer cases, the number-one cancer killer of
both men and women18. Smoking is also associated with cancers of the mouth,
pharynx, larynx, esophagus, stomach, pancreas, cervix, kidney, ureter, and
bladder7.
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. More than 90 percent of all deaths from
chronic obstructive pulmonary diseases are attributable to cigarette smoking.
It has also been well documented that smoking substantially increases the risk
of heart disease, including stroke, heart attack, vascular disease, and
aneurysm7. It is estimated that smoking accounts for approximately 21 percent
of deaths from coronary heart disease each year16.
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 death19. 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.
Approximately 440,000 Annual Deaths are Attributable to
Cigarette Smoking
While 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 disease7. Exposure to tobacco smoke in
the home is also a risk factor for new cases and increased severity of
childhood asthma and has been associated with sudden infant death syndrome.
Additionally, dropped cigarettes are the leading cause of residential fire
fatalities, leading to more than 1,000 deaths each year20.
Are there safe tobacco products?
The adverse health effects of tobacco use are well known,
yet many people do not want to quit or have difficulty quitting. As a result,
there has been a recent surge in the development of tobacco products that claim
to reduce exposure to harmful tobacco constituents or to have fewer health
risks than conventional products. These “potentially reduced exposure products”
(or 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 disease21. Recent
studies indicate that the levels of carcinogens in these PREPs range from
relatively low to comparable to conventional tobacco products22,23. These
studies conclude that medicinal nicotine (found in the nicotine patch and gum)
is a safer alternative than these modified tobacco products.
WARNING: There is no safe tobacco product. The use of any
product–including cigarettes, cigars, pipes, and spit tobacco; mentholated,
"low tar," naturally grown" or "additive free"–can
cause cancer and other adverse health effects.
Smoking and pregnancy—What are the risks?
In the
United
States, it is estimated that 18 percent of
pregnant women smoke during their pregnancies1. Carbon monoxide and nicotine
from tobacco smoke may interfere with the oxygen supply to the fetus. Nicotine
also readily crosses the placenta, with concentrations in the fetus reaching as
much as 15 percent higher than maternal levels24. 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 200115, and neonatal care costs related to smoking are estimated to be
more than $350 million per year7,25.
The adverse effects of smoking during pregnancy can include
fetal growth retardation and decreased birth weights. The decreased birth
weights 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 birth weight26,27. These newborns also display signs of
stress and drug withdrawal consistent with what has been reported in infants
exposed to other drugs28. In some cases, smoking during pregnancy may be
associated with spontaneous abortions, sudden infant death syndrome, as well as
learning and behavioral problems in children. In addition, smoking more than a
pack a day during pregnancy nearly doubles the risk that the affected child
will become addicted to tobacco if that child starts smoking29.
Are there gender differences
in tobacco smoking?
Several avenues of research now indicate that men and women
differ in their smoking behavior. For instance, women smoke fewer cigarettes
per day, tend to use cigarettes with lower nicotine content, and do not inhale
as deeply as men. However, it is unclear whether this is due to differences in
sensitivity to nicotine or other factors that affect women differently, such as
social factors or the sensory aspects of smoking.
The number of smokers in the
United States declined in the 1970s
and 1980s, remained relatively stable throughout the 1990s, and 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 women30. Several factors appear to be contributing to this
narrowing gender gap, including increased initiation of smoking among female
teens and women being less likely than men to quit31.
Large-scale smoking cessation trials show that women are less
likely to initiate quitting and may be more likely to relapse if they do
quit30. 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 men31. 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 gain32. 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 success33,34.
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.
Smoking and adolescence
There are nearly 4 million American adolescents who have
used a tobacco product in the past month1. Nearly 90 percent of smokers start
smoking by age 18, and of smokers under 18 years of age, more than 6 million
will die prematurely from a smoking-related disease35.
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. Indeed, even
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 animals36.
Adolescents may also be more sensitive to the reinforcing
effects of nicotine in combination with other chemicals found in cigarettes,
thus increasing susceptibility to tobacco addiction. As mentioned above,
acetaldehyde increases nicotine’s addictive properties in adolescent, but not
adult, animals. That is, adolescent animals performing a task to receive
nicotine showed greater response rates to nicotine when combined with acetaldehyde14.
NIDA continues to actively support research aimed at increasing our
understanding of why and how adolescents become addicted, and to develop
prevention, intervention, and treatment strategies to meet the specific needs
of teens.
Are there effective treatments for tobacco addiction?
Forms of TreatmentYes, extensive research has shown that
treatments for tobacco addiction do work. Although some smokers can quit
without help, many individuals need assistance in 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 5.1 years37.
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 tobacco12. An added benefit is that these forms
of nicotine have little abuse potential since they do not produce the
pleasurable effects of tobacco products—nor do they contain the carcinogens and
gases associated with tobacco smoke. Behavioral treatments, even beyond what is
recommended on packaging labels, have been shown to enhance the effectiveness
of NRTs and improve long-term outcomes.
The FDA’s approval of nicotine gum in 1984 marked the
availability (by prescription) of the first NRT on the
U.S. market. In
1996, the FDA approved Nicorette gum for over-the-counter (OTC) sales. Whereas
nicotine gum provides some smokers with the desired control over dose and the ability
to relieve cravings, others are unable to tolerate the taste and chewing
demands. In 1991 and 1992, the FDA approved four transdermal 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 major focus of pharmacological treatments for
tobacco addiction has been nicotine replacement, other treatments are also
being studied. 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 new medication that recently received FDA approval for
smoking cessation. This medication, which acts at the sites in the brain
affected by nicotine, may help people quit by easing withdrawal symptoms and
blocking the effects of nicotine if people resume smoking.
Several other nonnicotine medications are being investigated
for the treatment of tobacco addiction, including other antidepressants and an
antihypertensive medication, among others. 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. They
employ a variety of methods to assist smokers in 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, as well as increase social support. Research has also shown that the
more therapy is tailored to a person’s situation, the greater the chances are
for success.
Traditionally, behavioral approaches were developed and
delivered through formal settings, such as smoking-cessation clinics and
community and public health settings. Over the past decade, however,
researchers have been adapting these approaches for mail, telephone, and
Internet formats, which can be more acceptable and accessible to smokers who
are trying to quit. In 2004, the U.S. Department of Health and Human Services (HHS)
established a national toll-free number, 800–QUIT–NOW (800–784–8669), to serve
as a single access point for smokers seeking information and assistance in
quitting. Callers to the number are routed to their state’s smoking cessation
quitline or, in states that have not established quitlines, to one maintained
by the National Cancer Institute. In addition, a new HHS Web site
(www.smokefree.gov) offers online advice and downloadable information to make
cessation easier.
Quitting smoking can be difficult. While people can be
helped during the time an intervention is delivered, most intervention programs
are short-term (1–3 months). Within 6 months, 75–80 percent of people who try
to quit smoking relapse11. 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 year38.
Glossary
Addiction: A chronic, relapsing disease characterized by
compulsive drug seeking and abuse and by long-lasting neurochemical and molecular
changes in the brain.
Adrenal glands: Glands located above each kidney that
secrete hormones, e.g., adrenaline.
Craving: A powerful, often uncontrollable desire for drugs.
Dopamine: A neurotransmitter present in regions of the brain
that regulate movement, emotion, motivation, and feelings of pleasure.
Emphysema: A lung disease in which tissue deterioration
results in increased air retention and reduced exchange of gases. The result is
difficulty breathing and shortness of breath.
Hyperglycemic: The presence of an abnormally high
concentration of glucose in the blood.
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
responsible for smoking’s psychoactive and addictive effects.
Pharmacokinetics: The pattern of absorption, distribution,
and excretion of a drug over time.
Rush: A surge of euphoria that rapidly follows
administration of some drugs.
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.
References
1 Substance Abuse and Mental Health Services Administration.
Results from the 2004 National Survey on Drug Use and Health: National
Findings. DHHS Pub. No. SMA 05-4062, 2005.
2 Giovino GA, Henningfield JE, Tomar SL, Escobedo LG, Slade
J. Epidemiology of tobacco use and dependence. Epidemiol Rev 17(1):48–65, 1995.
3 National Institute on Drug Abuse. Monitoring the Future,
National Results on Adolescent Drug Use, Overview of Key Findings 2005. NIH
Pub. No. 01-4923, 2005.
4 Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick
D, Bor DH. Smoking and mental illness. A population-based prevalence study.
JAMA 284:2606–2610, 2000.
5 Breslau N. Psychiatric comorbidity of smoking and nicotine
dependence. Behav Genet 25:95–101, 1995.
6 Hughes JR, Hatsukami DK, Mitchell JE, and
Dahlgren LA.
Prevalence of smoking among psychiatric outpatients. American Journal of
Psychiatry 143:993-997, 1986.
7 U.S. Department of Health and Human Services. The Health
Consequences of Smoking: A Report of the Surgeon General. Atlanta, Georgia:
U.S. Department of Health and Human Services, Centers for Disease Control and
Prevention, National Center for Chronic Disease Prevention and Health
Promotion, Office on Smoking and Health, 2004.
8 Federal Trade Commission. "Tar," nicotine, and
carbon monoxide of the smoke of 1294 varieties of domestic cigarettes for the
year 1998. Federal Trade Commission, 2000.
9 Benowitz NL. Pharmacology of nicotine: addiction and
therapeutics. Ann Rev Pharmacol Toxicol 36:597–613, 1996.
10 Bornemisza P, Suciu I. Effect of cigarette smoking on the
blood glucose level in normals and diabetics. Med Interne 18 :353-6, 1980.
11 U.S. Department of Health and Human Services. Reducing
Tobacco Use: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department
of Health and Human Services, Centers for Disease Control and Prevention,
National Center for Chronic Disease Prevention and Health Promotion, Office on
Smoking and Health, 2000.
12 Henningfield JE. Nicotine medications for smoking
cessation. New Engl J Med 333:1196–1203, 1995.
13 Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J,
MacGregor R, Alexoff D, Shea C, Schlyer D, Wolf AP, Warner D, Zezulkova I,
Cilento R. Inhibition of monoamine oxidase B in the brains of smokers. Nature
22:733–736, 1996.
14 Belluzzi JD, Wang R, Leslie FM. Acetaldehyde enhances
acquisition of nicotine self-administration in adolescent rats.
Neuropsychopharmacology 30:705–712, 2005.
15 Centers for Disease Control and Prevention (CDC).
Morbidity and Mortality Weekly Report (MMWR) 54(25):625–628, 2005.
16 U.S. Department of Health and Human Services. Reducing the
Health Consequences of Smoking. Atlanta, Georgia: U.S. Department of Health and
Human Services, Centers for Disease Control and Prevention, National Center for
Chronic Disease Prevention and Health Promotion, Office on Smoking and Health,
1989.
17 Centers for Disease Control and Prevention (CDC).
Morbidity and Mortality Weekly Report (MMWR) 31(7):77–80, 1982.
18 American Cancer Society. Cancer Facts and Figures, 2005.
http://www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf
19 Riordan M, Rylance G, Berry K. Poisoning in children 5:
rare and dangerous poisons. Arch Dis Child 87:407-10, 2002.
20 Centers for Disease Control and Prevention (CDC).
Morbidity and Mortality Weekly Report (MMWR) 51(14):300–303, 2002.
21 Institute of Medicine (IOM). Clearing the smoke: assessing
the science base for tobacco harm reduction, pp. 5, 2001.
22 Stepanov I, Jensen J, Hatsukami D, Hecht SS.
Tobacco-specific nitrosamines in new tobacco products. Nicotine Tob Res
8:309–313, 2006.
23 Hatsukami DK, Lemmonds C, Zhang Y, Murphy SE, Le C,
Carmella SG, Hecht SS. Evaluation of carcinogen exposure in people who used
"reduced exposure" tobacco products. J Nat'l Cancer Inst. 96:844-52,
2004.
24 Huizink AC, Mulder EJH. Maternal smoking, drinking or
cannabis use during pregnancy and neurobehavioral and cognitive functioning in
human offspring. Neurosci and Biobehav Reviews 30:24-41, 2006.
25 Adams EK, Miller VP, Ernst C, Nishimura BK, Melvin C,
Merritt R. Neonatal health care costs related to smoking during pregnancy.
Health Economics 11:193-206, 2002.
26 Ernst M, Moolchan ET, Robinson ML. Behavioral and neural
consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc
Psychiatry 40:630-641, 2001.
27 Fried PA, Watkinson B, Gray R. Growth from birth to early
adolescence in offspring prenatally exposed to cigarettes and marijuana.
Neurotox Teratol 21:513-525, 1999.
28 Law KL, Stroud LR, LaGasse LL, Niaura R, Liu J, Lester BM.
Smoking during pregnancy and newborn neurobehavior. Pediatrics 111:1318-1323,
2003.
29 Buka SL, Shenassa ED, Niaura R. Elevated risk of tobacco
dependence among offspring of mothers who smoked during pregnancy: a 30-year
prospective study. Am J Psychiatry 160:1978–1984, 2003.
30 Perkins KA, Donny E, Caggiula AR. Sex differences in
nicotine effects and self-administration: review of human and animal evidence.
Nic and Tobacco Res 1:301-315, 1999.
31 Perkins KA. Smoking cessation in women. Special
Considerations. CNS Drugs 15:391-411, 2001.
32 Perkins KA et al. Cognitive-behavioral therapy to reduce
weight concerns improves smoking cessation outcome in weight-concerned women. J
Consult Clin Psychol 69(4):604–613, 2001.
33 Evins AE, Mays VK, Rigotti NA, Tisdale T, Cather C, Goff
DC. A pilot trial of bupropion added to cognitive behavioral therapy for
smoking cessation in schizophrenia. Nicotine Tob Res 3:397–403, 2001.
34 O'Malley SS, Cooney JL, Krishnan-Sarin S, Dubin JA, McKee
SA, Cooney NL, Blakeslee A, Meandzija B, Romano-Dahlgard D, Wu R, Makuch R,
Jatlow P. A controlled trial of naltrexone augmentation of nicotine replacement
therapy for smoking cessation. Arch Intern Med. 166:667-674, 2006.
35 Centers for Disease Control and Prevention. Quick facts:
economic and health burden of chronic disease. http://www.cdc.gov/nccdphp/press/index.htm.
36 Levin ED, Rezvani AH, Montoya D, Rose JE, Swartzwelder HS.
Adolescent-onset nicotine self-administration modeled in female rats.
Psychopharmacol 169:141-149, 2003.
37 U.S. Department of Health and Human Services. The Health
Benefits of Smoking Cessation: A Report of the Surgeon General. Atlanta,
Georgia: U.S. Department of Health and Human Services, Centers for Disease
Control and Prevention, National Center for Chronic Disease Prevention and
Health Promotion, Office on Smoking and Health, 1990.
38 Hall SM, Humfleet GL, Reus VI, Munoz RF, Cullen J.
Extended nortriptyline and psychological treatment for cigarette smoking. Am J
Psychiatry 161:2100-2107, 2004.
http://www.nida.nih.gov/ResearchReports/Nicotine/Nicotine.html