NICOTINE

OFFICIAL NAMES: Nicotine, tobacco

STREET NAMES: Cigarettes, pipes, cigars, bidis (beedies), kreteks (clove cigarettes), spit tobacco (spit), chewing tobacco (chew), snuff

DRUG CLASSIFICATIONS: Not scheduled, stimulant

OVERVIEW

Nicotine dependence is almost invariably caused by addiction to tobacco, because tobacco is the overwhelming source of nicotine. Nicotine present within tobacco products causes physical and mental effects rapidly leading to addiction, and the user continues using tobacco despite adverse health consequences and usually a desire to stop. The widespread use of tobacco, despite its known dangers, probably reflects its low cost and easy availability, its high level of social acceptance until recent years, and its seemingly mild immediate side effects.

Nicotine use often begins in adolescence in response to commercial and social pressures and continues because of the positively reinforcing effects of nicotine, which can include both relaxation and increased alertness. In later stages of use, smoking may be used mainly to relieve withdrawal symptoms such as irritability and discomfort.

Addictive characteristics of nicotine

Nicotine meets the criteria for causing chemical dependence with the following characteristics:

• Users can exhibit tolerance, which is when additional amounts of nicotine are required to produce an effect.
• A great deal of time may be spent using nicotine (such as leaving work for cigarette breaks), and it is usually taken in larger amounts or over longer periods of time than was intended.
• Users may have a persistent desire for nicotine (craving) and unsuccessful attempts to cut down or control its use.
• Nicotine causes withdrawal symptoms, and its ingestion may continue despite knowledge of the harm it causes.
• Daily tobacco use becomes compulsive, repetitive, and imperative.
• The user avoids withdrawal symptoms and experiences the rewards by repeated dosing, that is, by ingesting more nicotine from tobacco products.
• There is a high rate of relapse once use ceases.

Nicotine dependence resembles that of alcohol, heroin, and cocaine but appears to be more harmless to smokers for two reasons. First, there are usually several years or decades before signs of disease are detected. Second, smoking does not produce a disabling state of intoxication seen with the other drugs. On the contrary, nicotine may improve attention or decrease fatigue and therefore improve performance.

Increased risk of developing dependence

Risk of dependence and disease increases with the number of cigarettes smoked and duration of smoking. There is a marked increase in dependence when use exceeds five cigarettes daily. The earlier individuals start to smoke, the more severe their addiction will be.

People with anxiety and depression are at greater risk of dependence as nicotine is used as a "self-medication" to enhance mood. Youths with adjustment problems, who are risk takers, or have extraverted (outgoing) personalities are at increased risk for smoking. Children whose parents are regular smokers are at high risk.

Genetic factors influence the risk of nicotine addiction, as with other addictive substances. Inheriting certain genes can either contribute to or help protect individuals from nicotine addiction. In some cases, the genetic vulnerability to nicotine addiction may be linked to a similar vulnerability to alcohol dependence. Genetic differences in dopamine receptors and rate of nicotine breakdown have been shown to effect the likelihood of nicotine dependence.

Introduction into society

Ingestion of nicotine is an ancient and widespread practice. Native North, Central, and South Americans have smoked, chewed, sniffed, and drank tobacco preparations for thousands of years. It was used in religious and ceremonial rituals, as a medication, and to suppress hunger. The word tobacco is derived from tobaga pipes used by Central American natives.

Christopher Columbus brought the practice back to Europe where it was first used for its medicinal properties. French diplomat Jean Nicot, for whom nicotine is

named, helped popularize its use to treat a wide array of illnesses: upset stomachs, ulcers, headaches, toothaches, constipation, and asthma. It was also used as a poultice and antiseptic for cuts, burns, and sores.

Nonmedical pipe smoking, chewing, and snuff were initially limited to sailors who had adopted the Native American habit but spread rapidly from Europe to Africa and Asia in the early 16th century. At the same time, there was strong condemnation of tobacco use on both health and social grounds. Popes and kings banned its use, perhaps slowing its spread as its popularity increased.

The commercial tobacco industry in North America began in the Jamestown colony in 1612 and grew to be one of the most important national crops over the next 200 years. By the early 1960s pipe smoking and snuff gave way to cigars and cigarettes with the development of a cigarette-rolling machine and the safety match. Cigarette consumption increased during both World Wars, and mass marketing caused a dramatic jump in cigarette use during the next several decades.

The height of the smoking epidemic in the United States was in 1965 when 52% of adult men and 32% of adult women smoked. Attitudes of Americans had slowly begun to change by the 1950s when long-term studies clearly linked tobacco and disease. Progress was made nationwide to decrease smoking rates using public health announcements on television, education in schools, increases of federal excise taxes, and warning labels on cigarette packages. In 1971 cigarette advertising was banned from television and radio, and during that same year the nonsmokers' rights movement began. Social acceptability of smoking began to fall, reinforced by the 1986 Surgeon General's report focusing on the hazards of environmental tobacco smoke to nonsmokers. By the end of the century, less than 25% of adults smoked, but the rate of decline slowed dramatically in the 1980s and 1990s for both men and women.

General impact today

Tobacco use, particularly smoking, is the number one cause of preventable death in the United States, causing 20% of all deaths. Smoking is a major risk factor for heart disease, stroke, lung and other forms of cancer, and chronic lung diseases—all leading causes of death. It is a major risk factor for a variety of other medical conditions as well.

There are at least 434,000 deaths attributable to smoking per year in the United States, almost 1,200 per day, one every 73 seconds. This death rate is higher than the combined total of deaths due to AIDS, alcohol, cocaine, heroin, homicide, suicide, motor vehicle crashes, and fires. Approximately half of all continuing smokers die from diseases caused by smoking. Of these, approximately half die between the ages 35 and 69, losing an average of 20 to 25 years of life expectancy. Continued smoking throughout life doubles age-specific mortality rates, nearly tripling them in late middle age.

Estimates of disease due to smoking do not include the contribution of smoking to overall poor health status. Poor general health may decrease survival for many diseases, including those not caused by smoking, and may limit the treatment options available to the patient. For example, a smoker with emphysema may not be a safe candidate for a surgery needed to treat another medical problem.

Reducing tobacco use

Despite overwhelming evidence for the adverse health effects of tobacco use, smoking habits have been difficult to change. Nicotine addiction, along with heavy promotion by the tobacco industry, maintains high levels of use. The Centers for Disease Control and Prevention (CDC) estimates that the average 14-year-old has been exposed to more than $20 billion in advertising since age six, creating a "friendly familiarity" with tobacco products. In1999, total advertising and promotional spending by the tobacco companies rose to $8.24 billion, more than $22 million per day. However, education, combined with community-wide and media-based activities, can postpone or prevent smoking onset in 20% to 40% of adolescents.

Studies show that the best ways to reduce tobacco use combine:

• restrictions or outright bans on tobacco advertising and promotion
• raising excise taxes on tobacco products
• enforcement of smoke-free environments in public areas and worksites
• banning of tobacco sales in vending machines
• warning labels on tobacco products and advertisements
• continuous education, especially for minors, on health effects of smoking
• a minimum age of 18 for sellers of tobacco products
• citation of storeowners who sell tobacco to minors
• licensing of tobacco-selling establishments plus compliance checks

The FDA was unsuccessful in its attempt from 1995 to 2000 to have nicotine named as a drug and cigarettes named as a drug delivery device and thus subject to FDA control. Such control would have had the potential to severely restrict promotion and access to tobacco products.

CHEMICAL/ORGANIC COMPOSITION

Nicotine (C₁₀ H₁₄ N₂, beta-pyridyl-alpha-N methylpyrrolidine) is a very poisonous, water-and lipid-soluble, liquid alkaloid with a burning taste. It is colorless, but turns brown and takes on the odor of tobacco upon exposure to air. First isolated in 1828, it is used as an insecticide in agriculture, and as a killer of parasites in veterinary medicine.

Tobacco plant leaves of two species, Nicotiana tobacum and the milder flavored Nicotiana rusticum, generally contain 2–8% nicotine. The average cigarette contains between 8 and 10 mg. Some nicotine is lost from the tobacco leaf during the curing (slow drying in sun, hot air, or smoke), storing, and manufacturing processes. The NCI points out that each can of chewing tobacco holds a lethal dose of nicotine. Also, each tin of snuff delivers as much nicotine as 30–40 cigarettes, with4.5–6.5 mg nicotine per pinch. Holding a pinch of snuff in the mouth for 20–30 minutes yields nicotine levels two to three times the amount of nicotine delivered by a regular-size cigarette.

Burned tobacco contains some 4,800 distinct chemicals in either gas or particle phases. Many of the compounds in both phases are highly reactive, poisonous, and toxic. Harmful products include oxidants and poisons produced during burning, as well as radioactivity, heavy metals, and pesticides that may have accumulated within the tobacco leaf. Sixty-nine of these substances are known to cause cancer in humans and animals, and many others are known to be strong irritants.

The gaseous phase contains the harmful gases carbon monoxide (CO) and nitrogen oxide, along with carbon dioxide, ammonia, hydrogen cyanide, benzene,

toluene, formaldehyde, acetone, acetaldehyde, methanol, and vinyl chloride. CO is a byproduct of the incomplete burning of tobacco and is thought to be a major culprit in causing cardiovascular (heart) disease.

The compounds of the particle phase are collectively called tar, or total particulate matter (TPM). Tar is the oily residue left behind when moisture evaporates from burned tobacco. It contains thousands of compounds, including cancer-causing aromatic amines, nitrosamines, and polycyclic aromatic hydrocarbons that are present in both smoking and smokeless tobacco. Other harmful constituents include radioactive lead and polonium as well as arsenic, among others.

Additives

The manufacturers of tobacco products add fillers, flavor enhancers, preservatives, and other additives to make the product more desirable to consumers, especially low-tar brands. Each company's list of additives was a closely guarded trade secret until 1984, when the lists were submitted to the government. The public was barred from seeing the lists until 1994. The initial list contained 700 potential additives, of which 13 are not allowed in food. One additive, ammonia, may be included to boost the absorption of nicotine and enhance the addictive "kick." Sweeteners and chocolate may help make cigarettes more attractive to children and first-time users.

Menthol is commonly added to certain brands as it numbs the throat to the irritating effects of smoke. Menthol opens up the lung passages and allows more smoke to be inhaled deeper into the lungs. It makes the lungs more permeable to tars and carcinogens (cancer-causing agents), causing greater disease. These cigarettes also boost nicotine and CO levels. Menthol cigarettes accounted for 26% of the market in 1999.

Low tar and nicotine cigarettes and compensatory smoking

In the 1950s tobacco companies introduced filters on cigarettes to try to remove some of the toxins in smoke. By 1999, 98% of United States smokers used filter-tipped cigarettes. The companies then made other changes to the cigarette to further reduce the amount of tar and nicotine delivered to the smoker. Such changes included altering the composition of the tobacco and adding ventilation holes in the filter to dilute smoke with air. The average tar yield has fallen from 37 mg to 12 mg since 1968. The average nicotine yield fell from 2.7 mg to 0.85 mg.

In theory, filters and other changes to decrease the amount of tar and nicotine in cigarettes should decrease the health hazards of smoking. In fact, the mortality risk among current smokers has risen in the last 40 years even though tar and nicotine levels have fallen. Many smokers of low-yield brands compensate by taking deeper, longer, or more frequent puffs from their cigarettes to get the nicotine their body desires. They may hold the smoke longer in their lungs before exhaling or smoke the cigarette further down. This is referred to as "compensatory smoking." They may also increase the amount of tar and nicotine taken into the lungs by unintentionally blocking tiny ventilation holes in the filter with their fingers or lips. The smoker may end up inhaling as much or more tar and nicotine as in regular brands. Additionally, low tar products may also have higher levels of CO, and a variety of other toxins.

Kreteks and bidis

Increasing numbers of teens are turning to alternative cigarettes called bidis, tiny flavored cigarettes from India, and kreteks or clove cigarettes from Indonesia. Bidis (or beedies) are small, unfiltered cigarettes, handrolled in leaves. Flavorings such as chocolate, strawberry, and vanilla are added to the American versions of bidis to make them more appealing to minors. Bidis contain more than three times the amount of nicotine and five times the amount of tar than regular cigarette smoke. They are also puffed more frequently than regular cigarettes to prevent them from going out.

Kreteks contain tobacco and 40% shredded clove buds. They have a pleasant, sweet aroma of cloves, but have such high levels of tar, nicotine, and CO, that smoking one is equivalent to smoking 20 light American cigarettes. Eugenol, the local anesthetic in cloves, permits the inhalation of the harsh smoke.

INGESTION METHODS

Nicotine is ingested by smoking shredded tobacco in cigarettes, cigars, and pipes, or through smokeless tobacco. Smokeless tobacco comes in two major forms: snuff and chewing tobacco. Snuff is cured, ground tobacco manufactured in three varieties: dry, moist, and fine cut. Chewing tobacco is coarser than snuff and is also produced in three forms: loose-leaf, plug, and twist.

Today, moist snuff is usually taken orally, similar to chewing tobacco. Usually a pinch of snuff or a plug of chewing tobacco is placed between the gum and cheek, or the leaves or plug are chewed. Saliva mixes with the tobacco, and nicotine is absorbed through the lining of the mouth. This moist tobacco is referred to as a "chaw" or "quid" of chewing tobacco or a "dip" or "pinch" of snuff. It may be kept in the mouth for hours, and the user expectorates (spits out) the saliva that mixes with the tobacco. Dry snuff, which is less commonly used, is usually inhaled through the nose.

Absorption and metabolism

Nicotine is easily absorbed through all body surfaces including the lungs, oral and nasal passages, skin, and gastrointestinal tract. Absorption is influenced by the pH (acidity) of the smoke or chew. Cigarette smoke is acidic, and therefore the nicotine is best absorbed through the alveoli (tiny air sacs) of the lungs during deep inhalation. Cigar and pipe smokers typically do not inhale the alkaline smoke, and nicotine absorption, like that of smokeless tobacco, occurs through the lining of the mouth. Inhalation provides the quickest route of nicotine delivery to the brain and is therefore the most addictive. Absorption through the mouth is slower and through the skin slower yet.

Nicotine in chewing tobacco is absorbed in the first 10 minutes, with peak levels occurring within 30 minutes. The nicotine from a puff of cigarette reaches the brain within 10 seconds. With approximately 10 puffs per cigarette, a pack per day delivers 200 doses (hits) of this potent drug to the brain. The repeated, frequent peaks in nicotine levels in the brain and blood contribute to its addictiveness.

The smoke is 1% to 2% nicotine and approximately 1–3 mg of the drug reaches the smoker's bloodstream per cigarette. Half of the nicotine is eliminated from the blood in 30 to 120 minutes. This short half-life is the result of a portion of nicotine in the blood being metabolized (broken down or changed into other substances) in the liver, lungs, and other organs. Primarily, it is oxidized into cotinine, a less active substance. The kidney then rapidly removes nicotine and cotinine from the body.

The short half-life of nicotine contributes to its abuse potential. The initial effects drop off after a few minutes, causing the user to continue self-administering nicotine throughout the day to maintain pleasurable effects and prevent withdrawal symptoms. Studies clearly show that animals will self-administer nicotine intermittently to avoid both very low and very high levels of nicotine.

THERAPEUTIC USE

Nicotine is most often used in replacement therapy for tobacco addiction, but also has some potential uses to treat other conditions. It has been helpful in stopping bleeding in ulcerative colitis. Nicotine gum is being tested in conjunction with Tourette syndrome where it has been seen to lessen the severity and frequency of tics. Nicotine may reduce tremors in Parkinson's patients because it increases dopamine levels, which are reduced in these patients. It also improves attention in Alzheimer's patients. Nicotine is being studied for its effect on dystonias (movement disorders), chronic pain syndrome, sleep apnea, ulcers, attention deficit disorder, obesity, and chronic inflammatory skin disorders as well.

USAGE TRENDS

Scope and severity

Cigarette smoking is the most common substance use disorder in the United States. A billion cigarettes were produced in the entire United States in 1885. Today over one billion are smoked daily. Nationally, there were 48 million adult (18 years and older) smokers in 2001. The average smoker smokes 20 cigarettes per day.

Low-income adults smoke more than high-income adults. People with less education smoke more than those with college degrees. Habitual users of alcohol, cocaine, and heroin are more likely to be smokers too. More than 80% of alcoholics are smokers, and alcoholic drinkers are at least twice as likely to be smokers than are nondrinkers. The highest prevalence rates are seen with psychiatric patients: up to 88% of schizophrenics smoke, and approximately 50% of patients with anxiety, personality disorders, and depression smoke. Forty percent of adults with attention deficit hyperactivity disorder (ADHD) smoke.

However, the 2001 smoking rate of 25% is markedly decreased from the height of the smoking epidemic in 1965, when 42% of adults over 18 years old smoked. More than half of the smokers in the United States since the mid-1960s have quit. However, following years of steady decline, rates showed only modest declines in the 1990s.

The consumption of cigars has been increasing since 1993 with growing popularity among younger, affluent people. In 1998, 5% of adults had smoked a cigar product in the last month. Pipe smoking is in decline, with only 2% of men in partaking in 1991, and very uncommon usage among women. Pipe smoking is mainly found in men over the age of 45, who are also likely to be users of other tobacco products, especially cigarettes. National data from 1999 shows 6% of adult men and 1% of women use chewing tobacco or snuff. But the popularity of smokeless tobacco is increasing, especially among younger white males.

Gender trends

Historically, smoking became prevalent among men before women, but the gap between male and female smoking rates narrowed in the mid-1980s and has remained constant. The American 2001 smoking rate of 28% men and 22% women decreased from the 1965 peak, when 52% of men and 32% of women smoked. In developing countries, 48% of males smoke. Rates among women are substantially lower (7%) but increasing.

The prevalence of smoking during pregnancy has declined steadily in recent years, although 13–22% of pregnant women continue to smoke. Only about one third of women who stop during pregnancy are still abstinent one year after the delivery.

Studies indicate that men and women differ in their smoking behavior. Women tend to smoke fewer cigarettes per day than men, are more likely to use filtered or low-tar and -nicotine cigarettes, and inhale less deeply. Women are less likely to use smokeless tobacco, cigars, or pipes than men are. Correspondingly, lung cancer rates are lower in women than men. However, in 2001, the United States Surgeon General noted a 600% increase since 1950 in women's death rate from lung cancer, primarily caused by previous decades of cigarette smoking.

Age trends

Most tobacco users begin the habit in their teens. Initiation and addiction to smoking occurs in 90% of tobacco users by their eighteenth birthday. Every day in the United States, more than 6,000 young people try a cigarette, and almost 3,000 become regular smokers. First-time cigarette use is most likely to occur between ages 11 and 15, in sixth through tenth grade. A long-term national study found that 70% of high-school seniors who smoked as few as one to five cigarettes a day were still smoking five years later, and most were smoking more cigarettes per day. Tobacco is often the first drug used by young people who go on to use alcohol, marijuana, and other drugs.

In 1999, 44% of male students and 37% of female students reported using some form of tobacco (cigarettes, cigars, or smokeless tobacco) in the past month. Thirty-five percent of high-school students were current smokers, including 39% of white students, 33% of Hispanic students, and 20% of African American students. The 2000 rate of high school use of bidis was 5% and5.8% for kreteks.

Overall, the percentage of American high-school students who smoked increased through the mid-1990s after declining in the 1970s and 1980s. The CDC found that the sharpest rise in daily smoking rates began in 1988, the year the Joe Camel advertising campaign began. A study released in 2001 shows that high school smoking levels peaked in 1997 and have since made steady progress downward. The decline is attributed to several factors, including decreased advertising targeted at youth, increased anti-smoking advertising, and increased prices of cigarettes.

Adolescent boys are shifting from smoking to smokeless tobacco partly due to the mistaken belief that it is a safe substitute for smoking. Nationwide in 2000, 4% of middle school boys and 12% of high school boys used chewing tobacco or snuff. White male students were more likely than Hispanic or African American male students to use smokeless tobacco. The median age for first use of smokeless tobacco is 12, two years younger than the median age for first use of cigarettes.

An increasing number of boys and girls are experimenting with cigars, unaware that the risks are similar to cigarette smoking. In 1999, an alarming 25% of high school males, and 10% of high school females were using cigars. White students are more likely than African American students to smoke cigar products.

Ethnic trends

Multiple factors determine patterns of tobacco use among racial and ethnic minority groups in the United States: socioeconomic status, cultural characteristics, degree of assimilation into American culture, stress, biological elements, targeted advertising, price of tobacco products, and the varying capacity of communities to mount effective tobacco control initiatives.

Between 1983 and 1995, cigarette smoking declined for whites (34% to 26%), African Americans (37% to 27%), Hispanics (30% to 19%), and Asian and Pacific Islanders (24% to 15%). The prevalence of tobacco use among Native American and Alaskan Natives stayed at 41% between 1983 and 1995.

The American Heart Association smoking statistics for the year 2000 are as follows:

• Native American men: 38%; women: 31%
• African American men: 32%; women: 22%
• Caucasian American men: 27%; women: 23%
• Hispanic American men: 26%; women: 14%
• Asian and Pacific Islander American men: 22%; women: 12%

It is important to note that although African Americans do not have the highest smoking rates of racial groups in the United States, they appear to bear the greatest adverse health effects, particularly lung cancer in males. Some studies propose that the use of mentholated cigarettes by 80% of African Americans might be a cause.

Occupational and workplace trends

Professional, technical workers, and clergy have the lowest smoking rates whereas the military, law enforcement, and blue-collar workers have the highest rates. More adults are taking up the smokeless tobacco habit if they are no longer allowed to smoke on the job. Professional baseball players have an alarmingly high rate of 35% to 40% chewing tobacco use, and approximately half of those have pre-cancerous lesions of the mouth.

Larger employers with over 100 workers are more likely to adopt restrictive smoking policies, compared to smaller companies. Hospitality, service, and blue-collar workplaces in manufacturing and processing industries are less likely to be smoke-free environments.

Global trends

Tobacco use is one of the major causes of preventable death in the world. The estimated 1.2 billion smokers in the world consume an average of 14 cigarettes per day. In the year 2000, 4.2 million deaths were due to tobacco use, and the figure is expected to rise to 10 million deaths annually by the year 2030. Seven million of those deaths are expected to occur in developing countries. While smoking rates are slowly declining in developed nations, they are steadily growing in developing nations at a rate of 3.4% per year. Smoking will eventually kill about 500 million people alive in the world today. One billion people will die from tobacco in this century.

MENTAL EFFECTS

Nicotine has several effects that are due to its action on the brain. Beginning smokers may experience dizziness or lightheadedness and sometimes vertigo. At higher doses, nausea and vomiting may occur. These effects can also be elicited in chronic smokers with forced, rapid smoking. Most smokers learn to avoid such unpleasant effects by adjusting their inhalation patterns.

Studies have indicated that there are two major pleasurable effects of nicotine ingestion that reinforce the habit: stimulation (vigilance, wakefulness) and relaxation. Tobacco users may feel that smoking helps them concentrate and feel clear headed, and studies do show that nicotine causes an improvement in attention, recall, information processing, reaction time, and problem solving. Smokers may also feel that smoking helps them relax in stressful situations or that it lifts their mood. They may feel calm and experience less anger, tension, depression, and stress. Both stimulation and relaxation may be experienced at the same time, resulting in a state of relaxed wakefulness.

Nicotine is known to bind to acetylcholine receptors (the receiving areas on cells) that are located throughout the central nervous system as well as the peripheral nervous system. Acetylcholine is a neuro-transmitter: it transmits nerve impulses from one nerve fiber to another. The pleasurable effects of nicotine are a

direct result of nicotine binding to these acetylcholine receptors, which then triggers the release of other neurotransmitters and hormones. Epinephrine, dopamine, norepinephrine, acetylcholine, serotonin, vasopressin, and beta-endorphin are all released. Epinephrine (adrenaline) release results in a "rush" or "kick" as it stimulates the body, increasing heart rate, blood pressure, breathing rate, and blood sugar. The wide variety of chemical messengers in the following list adapted from Neal L. Benowitz (1999) may explain the diverse, and sometimes seemingly opposite effects of nicotine (stimulation and relaxation) reported by smokers:

• Dopamine causes pleasure and appetite suppression.
• Norepinephrine causes mental stimulation and appetite suppression.
• Acetylcholine causes mental stimulation and cognitive (thinking) enhancement.
• Vasopressin causes memory improvement.
• Serotonin causes mood enhancement and appetite suppression.
• Beta-endorphin causes a reduction of anxiety and tension.

Furthermore, nicotine may have different effects at different doses. Rapidly delivered, increasing doses are likely to cause a stimulating reaction, whereas slower, chronic intake has a more calming, sedating effect.

Nicotine is thought to cause addiction primarily through its action to increase the levels of dopamine, which activates the brain circuitry that regulates feelings of pleasure and motivation, the so-called reward system. Increased dopamine in this system produces pleasurable sensations, as seen in other drugs of abuse such as cocaine and heroin.

Substances in smoke other than nicotine may also affect the brain. An unknown substance in smoke causes a decrease in the level of monoamine oxidase (MAO), an important enzyme responsible for breaking down dopamine. The decrease in MAO results in higher dopamine levels, which contributes to the desire to keep smoking.

The desire to smoke can also be brought on by reinforcing factors called "external stimuli" such as the sight, taste, and smell of tobacco smoke, as well as the social setting and rituals associated with smoking. These previously neutral stimuli in the environment, or certain events, can become associated with tobacco use and thus become triggers for a desire to smoke.

PHYSIOLOGICAL EFFECTS

Immediate effects

As with the mental effects of nicotine, the physiological effects are brought about by its actions on the nervous system, both peripheral and central. Nicotine changes the transmission of nerve impulses by binding to acetylcholine receptors, and induces the release of several chemical messengers, which in turn affect several body systems.

In the cardiovascular system, there is a 10 to 20 beat per minute increase in heart rate, a 5–10 mm increase in blood pressure, and an increase in the strength of heart contractions. Nicotine increases the incidence of cardiac arrhythmia (irregular heartbeat) in susceptible people. It causes constriction of blood vessels in the skin, and causes platelets to adhere together leading to an increased possibility of blood clots.

Nicotine is irritating to the digestive tract. Salivation increases, and the strength of stomach contractions decreases. Nausea and vomiting may occur. Appetite is suppressed, particularly in females for sweet food. Metabolism is increased and brown fat is stimulated, which along with appetite suppression can lead to weight loss.

Nicotine causes local irritation in the respiratory system, as well as decreased motion of the cilia, the tiny hairs that sweep debris and mucus upward, out of the respiratory tract. A recurrent "smoker's cough" results as the body tries to rid itself of accumulated mucus. Breathing is accelerated by nicotine.

In the endocrine (gland secretion) system, besides increased release of epinephrine and norepinephrine, there is increased release of the growth hormone, cortisol, and the antidiuretic hormone. The increased levels of circulating catecholamines (epinephrine, norepinephrine, and dopamine) play a role in causing cardiovascular diseases by changing the balance of lipoproteins circulating in the blood. They increase the harmful low-density lipoproteins (LDL) and decrease the protective high-density lipoproteins (HDL), increasing the risk of cardiovascular disease.

Nicotine toxicity

Ingestion of 60 mg of nicotine can be fatal to an adult. This is an amount that might be ingested with exposure to some insecticide sprays. A smaller amount is toxic to children and pets who accidentally ingest tobacco products. Tobacco pickers and patients on nicotine replacement therapy who continue to smoke have also experienced nicotine toxicity. Symptoms include salivation, dizziness, vomiting, tremors, convulsions, and severely low blood pressure. Death may result in a few minutes due to respiratory failure caused by lung paralysis.

Carbon monoxide and tar

It is important to emphasize that although nicotine causes a wide variety of physical and mental effects, the majority of health problems from smoking are due to carbon monoxide and tar, much more so than nicotine. CO decreases the ability of the blood to carry oxygen. This leads to an increased production of red blood cells to compensate for the loss of oxygen carrying capacity. Along with nicotine, CO contributes to lipoprotein changes and increased blood-clotting ability, leading to cardiovascular disease. Tar, with its many known carcinogens and other irritants, is largely responsible for various forms of cancer, especially lung cancer.

Withdrawal syndrome

An attempt to stop using tobacco products, or even decrease their consumption, often results in the user experiencing unpleasant withdrawal symptoms that are due specifically to nicotine. Symptoms may start within hours after cessation of use, peak usually at the second to fourth day and may last for weeks or months.

Withdrawal symptoms include:

• restlessness
• anxiety
• impatience
• irritability or anger
• difficulty concentrating
• excessive hunger
• depression
• disorientation
• loss of energy or fatigue
• decreased heart rate and blood pressure
• dizziness
• stomach or bowel problems
• headaches
• sweating
• insomnia
• heart palpitations
• tremors
• decreased motor performance
• increased muscle tension
• craving for tobacco products

The symptoms are often worse in the evening. Weight gain is common, 4–7 lb (2–3 kg) on average.

Among tobacco users with no history of depression, 20% experience depression during withdrawal. The rate jumps to 80% for those with a past history of depression. Women are more prone to depression during withdrawal than men.

Long-term health effects

Smoking causes one third of all cancers and 87% of lung cancer. Because of tobacco use, lung cancer is the number one cancer killer of both men and women. It is also associated with cancer of the mouth, throat, voice box, esophagus, stomach, bladder, kidney, pancreas, uterus, and cervix. Smoking is also possibly linked to leukemia, and cancer of the breast, prostate, and colon. The overall rates of death from cancer are twice as high among smokers as among nonsmokers, with heavy smokers having death rates that are four times greater than nonsmokers. The role of nicotine itself in causing cancer is controversial.

The majority of smoking-related illnesses are cardiovascular and respiratory. Nearly one fifth of heart disease deaths in the United States are related to smoking. It is a major cause of atherosclerosis (narrowing and hardening of the arteries) and high blood pressure and the resulting angina, heart attacks, and strokes due to both hemorrhage and blood clots. It also increases the risk of abdominal aortic aneurysm.

Smoking leads to respiratory problems other than lung cancer. It causes chronic bronchitis, emphysema, and lower resistance to flu and pneumonia. It worsens asthma symptoms in adults and children. As these problems persist, chronic obstructive pulmonary disease (COPD, airway obstruction) develops. Eighty to 85% of deaths due to COPD are from smoking. The role of nicotine in chronic lung diseases such as COPD, emphysema, and asthma is uncertain. However it is known that nicotine can cause an enzyme to be released which is able to destroy parts of the lungs as is seen in emphysema.

Smoking is especially harmful to diabetics who are already at an increased risk of cardiovascular disease, stroke, and kidney disease. The habit also negatively affects joints and interferes with the healing of wounds. Healing of fractures is delayed because smoking impairs the formation of new bone. Smokers are more likely to develop degenerative disorders and injuries of the spine. The risk for peptic ulcers is increased. Smoking also may upset thyroid function.

Heavy smoking is a contributory factor in male impotence due to a decreased amount of blood flowing into the penis. Smoking also increases the risk of infertility in men by decreasing sperm motility and density. A nearly twofold increase in hearing loss, cataracts, and macular degeneration of the eye has been observed in smokers. Smokers have a decreased sense of taste and smell and are prone to periodontal disease, such as receding gums, as well as increased dental cavities.

Women

Women face additional adverse health effects from smoking. About 30% of cancers of the cervix are attributable to both active and passive smoking. Women who smoke have a high risk for osteoporosis and hip fractures following menopause. They are likelier to have early onset of menopause due to nicotine's anti-estrogen effect. However, the decreased estrogen levels seen in female smokers appear to decrease their risk of endome-trial cancer up to 50%. Women smokers have an increased risk of infertility, especially those women who started before age 18 or who smoke one or more packs per day. In 1987, lung cancer surpassed breast cancer as the leading cause of cancer death among women.

Pregnancy

Pregnant women who smoke create additional health concerns for their unborn child. Many substances in tobacco smoke, including nicotine, cross the placenta and are found in breast milk. Mothers who smoke heavily have almost a two-fold increase in miscarriage and birth defects and are more likely to deliver low-birth-weight babies. Smoking during pregnancy also causes ectopic pregnancy, premature births, and stillbirths. Infant mortality rates in pregnant smokers are increased 33%.

Sudden infant death syndrome (SIDS) is strongly linked to smoking in pregnant women and new mothers. Children of smoking mothers are more likely to have motor control problems, perception impairments, symptoms of hyperactivity, and conduct disorder in childhood. These children have a higher risk for cancer later in life.

Teens

The younger a person begins smoking, the greater the risk of developing serious illnesses. Smoking teens experience adverse health effects, including a general decrease in physical fitness, increased coughing and phlegm, greater susceptibility to respiratory illnesses, and early development of artery disease (a precursor to heart disease). They have a slower rate of lung growth, and by adulthood, possible reduced lung function.

Cigars and pipes

Cigars and pipes have health consequences similar to those of cigarettes, including nicotine dependence, heart disease, and cancer of the lung, mouth, throat, voice box, esophagus, prostate, bladder, and possibly the pancreas. Additionally, pipe smoking causes cancer of the lip. Inhaling cigar or pipe smoke significantly raises the risk of disease.

Smokeless tobacco

Smokeless tobacco causes cancer of the mouth, esophagus, and stomach. Users who swallow the tobacco or the saliva increase their risk of esophageal damage and stomach ulcers. Dentists report seeing users with leukoplakia (pre-cancerous lesions) in the mouth, receding gums, dental cavities, chronic mouth sores, with badly discolored teeth, and bad breath. Smokeless tobacco may also contain high levels of sodium, which may contribute to high blood pressure.

REACTIONS WITH OTHER DRUGS OR SUBSTANCES

Smoking causes the liver to produce more enzymes that break down a variety of drugs, resulting in lower than expected blood levels. It may be necessary to monitor smokers who take other drugs on a long-term basis, and adjust their doses during smoking cessation. These medications include asthma drugs such as theophylline (Slo-Bid, Theo-Dur), blood thinners such as warfarin (Coumadin), antipsychoitc drugs such as Clozapine (Clozaril), migraine drugs such as ergotamine, and some tricyclic antidepressants. Nicotine is also reported to decrease the blood-pressure-lowering effects of drugs such as nifedipine (Procardia), atenolol (Tenormin), and propanolol (Inderal).

Women who use birth control pills should not smoke as they are at increased risk for heart attacks, blood clots, stroke, liver cancer, and gallbladder disease. The risk increases with age (especially over the age of35) and smoking more than 15 cigarettes per day.

TREATMENT AND REHABILITATION

Nicotine and tobacco dependence is best treated as a chronic condition with remission and relapse. Up to 80% of tobacco users say they would like to quit. About one third of smokers try to quit each year, 90% of these without treatment, but only 2.5–5% are successful. Of those who try to quit without treatment, more than 90% fail, with most relapsing within a week. Most people experience relapses and require repeated attempts before achieving long-term abstinence. However, effective treatments do exist, and eventually 50% of smokers succeed in permanently quitting.

Attempts to quit tobacco use should focus on small steps toward future abstinence. Cigarette smokers who try to change to other forms of tobacco, such as pipes or cigars, are still at significant risk of disease. All forms of tobacco use entail serious adverse health effects and continued nicotine dependence. Turning to low-yield or smaller cigarettes, or smoking only part of a cigarette rarely works due to compensatory smoking.

A comprehensive treatment approach ideally has two parts: handling symptoms of withdrawal, and changing habits and social settings associated with tobacco use. The various forms of treatment include drug therapy, behavioral therapies, and general support. Drug treatment of nicotine addiction, combined with behavioral support, will enable 20–25% of users to remain abstinent one year following treatment. Several effective over-the-counter (OTC) and prescription drugs are available. Some medications involve significant cost, especially if a prescription is required, but are less expensive than the cost of continuing tobacco use.

Nicotine replacement therapy

The greatest danger of nicotine dependency is related mostly to the tobacco rather than nicotine itself. Nicotine replacement therapy (NRT) is far safer than tobacco use. Although the ultimate goal is to stop ingestion of nicotine, temporary nicotine replacement therapy is useful in dealing with withdrawal symptoms. Each type of NRT helps to approximately double the achievement of abstinence when used properly but should be combined with behavioral therapy and support. These forms of nicotine have little abuse potential since they do not produce the pleasurable effects of tobacco products. Seriously ill people, pregnant women, and breastfeeding women should consult a physician when considering NRT. All tobacco use should be avoided during NRT to prevent nicotine toxicity.

Nicotine gum (Nicorette) was introduced in 1984 and is currently sold without prescription in two and four mg doses. The user chews the gum briefly and then "parks" it between the cheek and gum so that nicotine can be absorbed through the lining of the mouth. Normally nicotine gum is used two to three months. Optimal usage may involve 10–20 pieces per day. Heavier smokers should use the four mg dose.

Nicotine skin patches (NicoDerm CQ, Nicotrol, Habitrol, ProStep) were introduced in 1991 and 1992, and are sold OTC or by prescription. Nicotine in the patch is absorbed through the skin (transdermally) in different strengths, for 16 or 24 hours a day. The release of nicotine through the skin is continuous and thus provides steady concentrations of nicotine in the blood. The 16-hour patch is removed at night for those experiencing sleeping difficulty. Patches are easy to use and only applied once per day; but dosing is not flexible, onset of symptom relief is slow, and mild irritation can occur at the patch site. Recommended use is six weeks with either constant or decreasing strengths.

Nicotine nasal spray (Nicotrol NS) requires a prescription. Introduced in 1996, the nasal spray delivers nicotine through the lining of the nose when it is squirted into each nostril once or twice an hour. This method provides the fastest delivery of nicotine of the currently available products and reduces cravings within minutes. However, this form has a greater potential for inappropriate use. Nose and eye irritation is common, but usually stops within one week.

Nicotine inhaler (Nicotrol Inhaler) requires a prescription. Introduced in 1998 and designed to look like a cigarette, the inhaler is a plastic cylinder holding a cartridge containing nicotine. Nicotine is absorbed through the lining of the mouth when the user puffs on the inhaler. Each cartridge lasts for 80 long puffs and is designed for 20 minutes of use. A minimum of six cartridges per day is needed for three to six weeks, when usage begins to taper off. This product mimics the hand to mouth ritual of smoking and delivers nicotine faster than the patch, but frequent use during the day is required, and mouth or throat irritation may occur.

Non-nicotine medication

In 1996 the FDA approved the antidepressant buproprion (Zyban) for the treatment of nicotine dependence. This sustained-release pill blocks nicotine's pleasurable effects and helps to maintain abstinence whether the user has depression or not. The length of suggested use is for seven to 12 weeks, including one to two weeks before quitting tobacco. Buproprion doubles the quit rate and has been demonstrated to be safe when used jointly with NRT.

Clonidine (Catapres), a high blood pressure medication, can be prescribed orally or as a patch for nicotine addiction and doubles the quit rate. It appears to reduce craving for tobacco but does not consistently reduce other withdrawal symptoms. The antidepressant nortriptylene (Pamelor) triples the quit rate. However, both have greater side effects than those previously listed, and are considered second-line therapies.

Other medications that have been studied for nicotine addiction but were found to yield poor or variable results include naltrexone, naloxone, lobeline, mecamylamine, and buspirone. Hypnosis and herbal remedies have been reported to be of potential use but are not scientifically proven. A review of nine studies of acupuncture therapy for smoking cessation shows it to increase the quit rate a modest 1.5 times.

Education, counseling, and behavioral strategies

Knowledge of the seriousness of adverse health effects due to tobacco use is helpful in motivating a user to quit, as well as maintaining abstinence. Physicians who advise their patients to quit smoking can produce cessation rates of 5–10%. Thus, education plays a critical role in tobacco cessation for all ages. A variety of self-help materials (books, tapes, pamphlets, newsletters, software, and Internet sites) are available to inform and aid in quitting tobacco use.

Having a strong motivation to quit tobacco use is usually not sufficient motivation to quit. Other key factors to successful cessation include avoiding smokers and smoking environments and receiving support from family and friends. Even then, most users will require some further assistance beyond self-help materials to successfully quit.

Individual and group counseling by trained therapists is beneficial to those trying to quit tobacco. Over the past decade, this approach has spread from primarily clinic-based, formal smoking-cessation programs to numerous community and public health settings. Two of the most widely available offerings are the American Cancer Society Fresh Start program and the American Lung Association Freedom From Smoking program. These group programs consist of multiple sessions using behavior modification techniques. The goals of behavioral methods are to reduce the reinforcing value of smoking, discover high-risk relapse situations, create an aversion to smoking, develop self-monitoring of smoking behavior, learn coping strategies, and establish alternative rewards. Coping skills are essential for both short-and long-term prevention of relapse. A form of aversive conditioning, called rapid smoking, leads to good quit rates but dangerously high blood nicotine levels.

Groups with problems quitting

Women and African Americans have greater difficulty quitting tobacco use. NRT does not seem to reduce craving as effectively for women as it does for men. Women seem to be less sensitive to nicotine than men, but more sensitive to external stimuli—the sight, smell, and touch involved in smoking. Women have greater concerns about weight gain, restrictions on medication during pregnancy, and influences of the menstrual cycle on mood. Cessation programs should be tailored for women to rely less on NRT and more on behavioral support.

African Americans are more likely than whites to try to quit smoking, but less likely to succeed. This group apparently metabolizes nicotine differently from other racial and ethnic groups. Nicotine uptake is almost 30% higher in African American smokers than white smokers, and elimination from the body is slower than with other groups. Higher nicotine blood levels over a longer period result in stronger nicotine dependence and more difficulty quitting.

Health benefits of smoking cessation

Immediate benefits of smoking cessation include a return to normal blood pressure and pulse rate. Levels of CO and oxygen in the blood return to normal within eight hours. Within 24 hours the chance of heart attack decreases, and within 48 hours nerve endings start to re-grow and the ability to taste and smell increases. In two to three weeks lung capacity has increased, and there is improved breathing and fewer respiratory ailments. In the next one to nine months, there is a decreased incidence of coughing, sinus infection, shortness of breath, and an increase in overall energy. Cilia re-grow in the airways, which increases the body's ability to handle mucus, clean the lungs, and reduce the chance of infection. There is reduced constriction of blood vessels in already diseased heart patients.

Heavy smokers and long-time smokers are at the greatest risk of disease, so they also have the most to gain from quitting. The decreased risk of disease varies with each disease state depending on how long the smoker has abstained. The risk of death from cardiovascular disease among former smokers approximates that of nonsmokers once the smoker has been tobacco-free for 15 years. The risk of death from lung cancer or COPD is essentially unchanged for the first five years following cessation but then declines steadily from five to 20 years. However, even beyond 20 years cessation, the risk of death due to lung cancer or COPD remains elevated above that of nonsmokers. Quitting smoking substantially decreases the risk of esophageal, mouth, voice box, pancreatic, bladder, and cervical cancers. Smokers who quit before age 50 cut their risk of dying in the next 15 years in half.

Cost effectiveness of treatment

Treating nicotine and tobacco dependence can prevent a variety of costly chronic diseases, including heart disease, cancer, and chronic lung disease. It is estimated that smoking cessation efforts are more cost effective than other commonly provided preventive services such as screening for breast, colon, and cervical cancer, treatment of mildly elevated blood pressure, and treatment of high cholesterol.

PERSONAL AND SOCIAL CONSEQUENCES

The personal consequences of nicotine dependence are clearly the potentially life threatening illnesses that tobacco causes. Additional negative consequences become evident as tobacco use becomes less socially acceptable. Unlike the use of other recreational drugs or alcohol, tobacco use does not alter consciousness or cause escape from social responsibility. Therefore, until recently, smoking was regarded as a matter of personal choice. The links between second-hand smoke and disease in nonsmokers altered that view. Smokers often must face isolation and the outdoor elements to avoid exposing family, friends, and coworkers to second-hand smoke. Even then, they may face negative feedback from those around them.

Smoking causes several cosmetic changes too. Tobacco stains teeth and fingers. Smoke odor on breath, clothes, and hair may be offensive to others. Smokers are nearly five times more likely to develop more and deeper skin wrinkles, and have a higher risk for baldness and prematurely gray hair.

Environmental tobacco smoke

The smoke from smoldering tobacco together with exhaled smoke are called environmental tobacco smoke (ETS), second-hand smoke, or passive smoke. ETS is classified by the Environmental Protection Agency as a class A carcinogen (proven cancer-causing substance). The smoldering tobacco, called "sidestream smoke," contains more toxic byproducts than the inhaled/exhaled "mainstream smoke," which is burned more completely as it is drawn through the cigarette.

ETS increases the risk of heart disease and lung conditions, especially asthma and bronchitis in children. In 2000, the National Cancer Institute (NCI) estimated that 3,000 lung cancer deaths, and as many as 40,000 cardiac deaths per year among adult nonsmokers in the United States can be attributed to ETS. Passive smoke also causes increased angina symptoms, allergic attacks, eye irritation, headaches, cough, and nasal symptoms. ETS is linked with low birth weight babies, sudden infant death syndrome (SIDS), and increased pneumonia and middle ear infections in children. More than 88% of nonsmokers in the United States, aged four years and older, have detectable levels of serum cotinine, an indication of ETS exposure.

Costs

Tobacco use has the highest cost to society of any substance of abuse, with the possible exception of alcohol. The American Lung Association estimated in the year 2000 that direct medical costs of tobacco-caused illness were approximately $50 billion. However, this cost is well below the total medical costs to society because it does not include such costs as burn care from smoking-related fires, and hospital care for low birth-weight infants of mothers who smoke.

Additionally, tobacco use creates an estimated $47 billion in indirect costs such as lost productivity. Smokers of one pack of cigarettes per day have 50% greater illness, absenteeism, and rate of hospitalization than nonsmokers. In 1996 the United States Department of Health and Human Services estimated the total cost of tobacco use to businesses to be more than $5,000 per employee per year

LEGAL CONSEQUENCES

Tobacco is a legal substance when purchased and used by adults. Despite widespread efforts to prevent minors from purchasing tobacco, a high proportion continues to do so. All 50 states ban the sale of tobacco to anyone under the age of 18, but many of the laws are weak and enforcement is generally poor. Various studies demonstrated that 32% to 87% of underage youths were able to purchase cigarettes over the counter.

A growing number of states and localities are imposing penalties, usually in the form of citations, against minors who purchase tobacco products. Less frequently, when the store is cited, the penalty is usually directed against the sales clerk rather than the business owner. The result is that the business owner, who sets store policy and gains financially from the illegal sale, is free from penalty.

A working group of States' Attorneys General recommended in 1994 that enforcement focus on commercial sellers of tobacco products before targeting the youth users. Most states already require licensing of stores selling tobacco, but the group further recommended unannounced compliance checks and graduated fines and license suspension for repeated sales to minors.

RESOURCES

Books

Baer, Andrea. Quit Smoking for Good. Freedom, CA: The Crossing Press, 1998.

Brigham, Janet. Dying To Quit, Why We Smoke and How We Stop. Washington, DC: Joseph Henry Press, 1998.

Fisher, Edwin B., and Toni L. Goldfarb. 7 Steps to a Smoke-Free Life, American Lung Association. New York: John Wiley & Sons, Inc., 1998.

Whelan, Elizabeth M. Cigarettes: What the Warning Label Doesn't Tell You: The First Comprehensive Guide to the Health Consequences of Smoking. Amherst, NY: Prometheus Books, 1997.

Periodicals

DeLucia, Anthony J. "Tobacco Abuse and Its Treatment." American Association of Occupational Health Nurse Journal 49, no.5 (May 2001): 243-259.

Lewis, C. "Every Breath You Take. Preventing and Treating Emphysema." FDA Consumer 33, no.2 (March-April): 9-13.

Other

Freedom From Smoking Online. American Lung Association online smoking cessation clinic. <www.lungusa.org/ffs/>.

TobaccoPedia: The Online Tobacco Encyclopedia.<http://tobaccopedia.org>.

U.S. Public Health Service. Centers for Disease Control and Prevention. Tobacco Information and Prevention Source (TIPS).<www.cdc.gov/tobacco/index.htm>. U.S. Public Health Service. Reports of the Surgeon General.<www.surgeongeneral.gov/library/reports.htm>

World Health Organization. Tobacco Free Initiative.<http://tobacco.who.int/>.

Organizations

American Lung Association, 1740 Broadway, 14th Floor, New York, NY, USA, 10019, (212) 315-8700, (212)265-5642, (800) 586-4872, <http://www.lungusa.org/tobacco>.

Office on Smoking and Health National Center for Disease Prevention and Health Promotion Centers for Disease Control and Prevention, (770) 488-5705, (770) 488-5705, <http://www.cdc.gov/tobacco>.

Marianne F. O'Connor, MT, MPH

Nicotine

What Kind of Drug Is It?

Nicotine is the ingredient in tobacco that causes changes to the brain and behavior. Tobacco, a broad-leafed plant that originated in the Americas, is one of the most widely abused psychoactive, or mind-altering, substances in the world. In the United States alone, one in four men and one in five women smoke cigarettes, cigars, pipes, or use oral products such as chewing tobacco or snuff. In other parts of the world the percentage of users is even higher.

Nicotine use typically begins among Americans between the ages of eleven and eighteen—an age group too young to buy the product legally. Young users soon discover that nicotine is habit-forming, that all the ways of taking it pose great health risks, and that it can lead to troubles on the job and sometimes an early death.

Movies and tobacco advertisements present nicotine use as a glamorous, rebellious, adult activity. And adults can smoke legally. What the advertisements do not note, however, is the fact that one-third of all smokers live below the poverty level; that the more educated a person is, the less likely he or she is to use tobacco; and that an estimated one billion people will die from tobaccorelated illnesses worldwide in the twenty-first century. Tobacco use is one of the leading causes of preventable death. Its link to cancer, emphysema and asthma (lung disorders), and depression (a mood disorder), has been clearly established. Smokers can expect to live seven to ten years less than people who do not use tobacco products.

Official Drug Name: Nicotine (beta-pyridyl-alpha-N-methylpyrrolidine), tobacco

Also Known As: Bidis (BEE-deez), chew, chewing tobacco, cigars, cigarettes, coffin nails, fags, kreteks, snuff, spit, smokes

Drug Classifications: Not scheduled, illegal for purchase by persons under eighteen years of age; stimulant

Popularity Decreases

At the height of tobacco's popularity in the United States in the 1960s, more than half of all adult men and about one in three adult women smoked cigarettes. People smoked in movie theaters and on buses and planes. They smoked at their desks in office buildings and in their beds at night. Famous film and television stars promoted certain brands of cigarettes in commercials and on billboards. Even in those times, however, people knew that smoking could ruin their health.

A half-century later, in the early 2000s, smokers can find it difficult to get a job if they reveal a tobacco habit. Smoking is not permitted on planes, in theaters, in many office buildings, or on public transportation. Many cities have enacted bans on smoking in restaurants and bars.

Studies have proven that secondhand smoke, or "passive" smoke, can cause many health problems for the nonsmoker. Pregnant women who smoke endanger the health of their unborn babies. Most Americans are less tolerant of smoking than they used to be. Yet, the "2003 National Survey on Drug Use and Health (NSDUH)" reported that 40 percent of young adults age eighteen to twenty-five admitted to smoking cigarettes at least once in their lives.

No country that has learned to use tobacco has ever given it up. Nicotine addiction, a physical dependence on the drug due

to repeated drug use, continues to be a global public health issue. It is one of the leading causes of preventable illness in adults. The U.S. government keeps a watchful eye on tobacco companies to ensure they do not target cigarette advertisements to teens for several reasons. First, teens are not allowed to smoke legally. Second, adults over the age of twenty-five rarely—if ever—begin smoking after never having smoked before.

Overview

The first European to record seeing tobacco use was the explorer Christopher Columbus (1451–1506), in 1492. On his initial voyage to the New World, Columbus wrote in his diary that the native peoples he encountered "drank" smoke from the burning leaves of a certain plant. Even without understanding their language, Columbus could see that the people he met highly valued their tobacco.

Use Originated in the Americas

Archaeologists are not sure where or when tobacco use began in the Americas. More than sixty varieties of tobacco grew all over North and South America. Even the garden flower known as the petunia is related to tobacco. The earliest documented use of tobacco among Native Americans occurred with the Mayan culture, a civilization from Central America that peaked about 2,000 years ago. A carving on a Mayan temple shows an elaborately dressed man smoking a long-stemmed pipe. Other historians of ancient America believe that pipe smoking may have begun in North America and spread south. Whatever the case, by 1000 ce, most Native American cultures used tobacco in religious and political rituals. The plant did not grow in Europe.

Columbus and his crew were baffled and disturbed by the sight of people smoking tobacco. Nevertheless, they collected specimens of the plant, as well as pipes, and took them back to Spain. As the Spanish and Portuguese began to explore and settle the Americas, they began "drinking smoke" themselves. Sailors who moved between Europe and America were among the first to discover that once they began smoking tobacco, they could not stop.

By 1535, Spanish colonists in the New World were planting tobacco for their own use. At around the same time, farmers in Europe began to cultivate the plant. In 1559, the French ambassador to Portugal, Jean Nicot (1530–1600), became interested in tobacco. He thought it might be useful as a medicine. He introduced powdered tobacco—snuff—at the French court and made the substance fashionable. It is from his name, "Nicot," that the word nicotine is derived.

Tobacco in the American Colonies

Tobacco was one of the first crops planted when English colonists arrived in Jamestown, Virginia. Ships filled with tobacco sailed from America to Europe, where the tobacco was traded for items the colonists could not make or buy in the New World, including tea, furniture, and high-quality cloth. In some parts of America, tobacco could be used instead of money. The need for new fields to grow tobacco—a plant that uses up the rich nutrients in the ground—pushed settlers westward, into territories occupied by Native Americans. By the time the Declaration of Independence was signed in 1776, tobacco smoking was common in America. Every tavern kept a supply of clay pipes for use by visitors. When smokers were finished with their pipes, they broke off the part of the stems their lips had touched and passed the pipe to a new user.

By the nineteenth century, different classes of people used tobacco in different ways. The upper classes tended to "take snuff," inhaling powdered tobacco through the nose. The middle classes preferred pipes, and the lower classes held wads of tobacco between their gums and teeth, a practice known as "chewing." Within 300 years of its discovery by Columbus, tobacco had spread to all parts of the world. Many cultures considered it a beneficial medicine. The Native Americans had wrapped shredded tobacco in larger leaves, and "cigars" became popular by the turn of the twentieth century. "Cigarettes" were invented by people who gathered the shredded cigar tobacco that had gone to waste and wrapped it in small papers to smoke it.

The popularity of cigarettes skyrocketed during World War I (1914–1918), because they were easy to transport into battle. Many young soldiers brought the cigarette habit home with them, and factories stood ready to create the product on assembly lines. By the 1920s, whole industries built on tobacco advertised in print, on billboards, and through movies and radio. Women were encouraged to smoke, and they took up the habit as well. The "Jazz Era" generation was the first to embrace tobacco in great numbers. The era's great athletes smoked when not on the playing field and chewed tobacco during games. During the Great Depression (1929–1941), U.S. President Franklin Delano Roosevelt (1882–1945) was sometimes photographed with a cigarette, in a holder, in his mouth.

Tobacco-Related Illness Begin to Surface

Americans who had been young in the 1920s were entering their sixties by the 1960s. At that time, tobacco use began to show its downside. Even as new generations became hooked on nicotine, older Americans suffered increasing numbers of lung, throat, and mouth cancers. Others died of emphysema, a disorder that affects the lungs' ability to process oxygen. In 1961 the Surgeon General of the United States requested a report on the effects of tobacco use on health. Facing opposition from tobacco companies—who claimed to have done their own research—a panel of experts met to study the problem.

In 1964 the panel submitted a report to the Surgeon General that linked tobacco use to lung cancer, mouth and throat cancer, heart attacks, strokes, emphysema, and other diseases of the stomach and liver. The report, to no one's surprise, declared that nicotine was habit-forming. At the time the report was issued, 40 percent of adult Americans used some form of tobacco.

By the late 1960s, nonprofit groups from many sectors were uniting to stop tobacco use in the United States. Groups such as the American Heart Association, the American Lung Association, and the American Cancer Society launched advertisements to counter the popular characters featured in cigarette ads, including Joe Camel and the Marlboro Man. Perhaps just as effective for younger people was the personal experience of a loved one—a parent, a grandparent, or an older sibling—suffering the ill effects of tobacco use. Smoking declined among the American public as a result.

The terms passive smoking and "secondhand smoke" had not been invented in the 1960s. However, by the 1990s people had become aware that tobacco smoke posed a threat not only to the smoker, but also to those exposed to the smoldering cigarette or cigar, and the exhaled smoke. Private companies began to ban smoking in office buildings, and a whole series of laws followed, banning smoking in public transportation, on airplanes, in health care facilities, and in government buildings. People who had once puffed at their desks were forced to smoke on their breaks, huddled outside in all sorts of weather. At the same time, states began to levy higher taxes on cigarettes to help pay for Medicaid and other social welfare programs.

Tighter Laws Cut Down on Nicotine Abuse

On November 16, 1998, forty-seven states and the District of Columbia came to an out-of-court settlement with four major American tobacco companies. (The other three states had previously come to agreements.) The states had sued the tobacco companies for the costs of providing health care to poor people suffering from tobacco-related illnesses. The cigarette companies agreed to pay the states $206 billion for health care. The companies also agreed not to market their product to adolescents through advertisements or promotional items. They further agreed to fund a program to discourage teenage smoking. One consequence of this settlement: The average price of a pack of cigarettes rose fifty cents in one year, from $2.20 in 1998 to $2.70 in 1999. By 2005, cigarettes were selling for about $4.00 per pack. For heavy smokers, many of them poor already, this was a difficult increase to manage.

Despite the successes made in the anti-tobacco campaign, smoking still appealed to youth who wanted to rebel against authority. In fact, by suggesting that tobacco was something that only adults should use just made it more popular with rebellious youth who wanted to seem hip and mature. Smoking was also glamorized in various movies as something that cool people do. As of the early twenty-first century, a large number of teens still take up smoking. The National Center for Chronic Disease Prevention and Health Promotion estimates that about 4,000 people under the age of eighteen begin smoking each day in the United States.

More recently, the healthcare industry has focused on smoking in films. "Product placement" is very important in movies. When a character in a film uses a particular food or beverage product, sales of that product often climb. In 2005 the American Medical Association recommended that the film industry adopt a policy that would automatically give an "R" rating to any movie in which a character uses tobacco. (People under seventeen are not supposed to be admitted to "R" rated movies without a parent or adult.) Whether the film industry will honor that request is uncertain.

What Is It Made Of?

Nicotine is a poisonous alkaloid that occurs naturally in the leaves of the tobacco plant. While still in the leaves of the plant, it is a colorless liquid. Sixty milligrams of nicotine, about the amount

a bottle cap would hold, can kill a human being. It is used as a pesticide to kill insects on plants and internal parasites in animals.

The chemical formula for nicotine is C₁₀H₁₄N₂. Theaverage cigarette contains 8 to 10 milligrams of nicotine, but much of this is lost in the process of burning. Typically, a smoker receives about 1 milligram of nicotine per cigarette. A pinch of chewing tobacco contains between 4.5 and 6.5 milligrams of nicotine. Since chewing tobacco enters the body more slowly than smoked tobacco, more of the dose is absorbed, but over a longer period of time.

In addition to nicotine, a smoking leaf of tobacco releases more than 4,000 different chemicals. Four hundred of these are known to be poisonous, and forty-three have been shown to cause cancer. A lit cigarette releases, among other things, carbon monoxide, ammonia, hydrogen cyanide, benzene, formaldehyde, acetone, methanol, and vinyl chloride. Tobacco companies add other ingredients to cigarettes as well, including menthol. Menthol numbs the throat to the irritating effects of the smoke. It also widens the pathways in the lungs, allowing more smoke to penetrate the tissues.

When smoke is exhaled from the lungs, a substance called tar remains in the body. As its name suggests, tar is a sticky residue that clings to lung tissue. Tar contains cancer-causing compounds. Receiving nicotine through the mouth by chewing reduces some of the dangerous chemicals from tar, but it also exposes the tissues in the mouth to cancer-causing agents and compounds that cause tooth decay and gum disease. The same compounds in tar simply cling to the mouth tissues and are absorbed by the gums, cheeks, and throat.

How Is It Taken?

Nicotine is taken in several ways. The most common and quick-acting manner is smoking. The user lights a cigarette, draws the smoke into the lungs, and exhales it. The effects of the nicotine can be felt within ten seconds, and they usually last between fifteen minutes and an hour.

Tobacco Statistics

Did you know that….

• As of 2005, tobacco use was considered to be the leading preventable cause of death in the United States. Nearly 500,000 deaths are related to tobacco use each year.
• The Centers for Disease Control and Prevention estimates that smoking takes 5.6 million years of potential life away each year in the United States.
• In the United States each day, some 4,000 people under age 18 smoke their first cigarette.
• Most adult smokers started using tobacco before their 18th birthday—nearly 80 percent of them, in fact.

People who smoke cigars and pipes generally "puff" them and do not inhale the smoke into the lungs. Even so, the soft tissues in the mouth absorb the nicotine and send it through the bloodstream to the brain. Smoking pipes or cigars is, indeed, habit-forming. Puffing is just another way to deliver nicotine to the brain. The presence of the smoke in the mouth and throat can lead to cancers in those body parts, and to cancer of the esophagus, the tube leading into the stomach.

With chewing tobacco, the user takes a wad of moist tobacco and presses it between the cheek and the gum. As the mouth fills with saliva, the user must spit, because swallowing tobacco-laced saliva could be deadly and certainly causes stomach upset. Users of chewing tobacco generally keep a wad in the mouth for about thirty minutes, during which time about 2 milligrams of nicotine enter the bloodstream through the cheek and gum tissue.

Few people snort snuff anymore, but it was once a popular way to use nicotine. Snuff, finely-ground tobacco, was snorted up the nose and usually removed by sneezing. A "pinch of snuff" was thought to ward off colds and other infectious diseases.

Are There Any Medical Reasons for Taking This Substance?

Some small studies have been performed to see if nicotine patches help reduce memory loss in alzheimer's disease patients and muscle tremors in parkinson's disease patients. Since nicotine is so highly addictive, however, its valid medical uses are considered very minimal.

The only acceptable medical use for nicotine is to help people overcome addiction to nicotine. "Nicotine delivery systems" include skin patches, gum, inhalers, and nasal sprays. Tobacco users trying to quit the habit can curb nicotine's withdrawal symptoms with these products. The products become very dangerous if a person smokes while using them. In that case, nicotine overdose is possible. Although some nicotine replacement products are available over the counter, most encourage nicotine addicts to seek the advice and counsel of a medical doctor while attempting to curb nicotine use.

Usage Trends

The American Heart Association Web site posts data on patterns of tobacco use among adults age eighteen and older in the United States. As of 2002, 25.2 percent of white American men and 20.7 percent of white American women used tobacco. In 2002, 27 percent of African American men and 18.5 percent of African American women used tobacco. Hispanic/Latino men reported 23.2 percent usage, and Hispanic/Latino women, 12.5 percent. Asian Americans were the least likely to use tobacco, with 21.3 percent of men and 6.9 of women reporting usage. The population most likely to use

tobacco, according to the American Heart Association data, is Native Americans/Alaskan Natives, who reported that 32 percent of adult men and 36.9 percent of adult women were tobacco users. The numbers add up to 47.5 million adult American users.

What the Surveys Say

The 2003 NSDUH found 70.8 million tobacco users in the United States, factoring in anyone over the age of twelve who had ever tried tobacco. Of these, the NSDUH characterized 35.7 million as nicotine addicts. This number includes Americans age twelve and older. The NSDUH data on teenage nicotine use does not break down by race or ethnic origin, reporting simply that 12.5 percent of girls age twelve to eighteen use tobacco, along with 11.9 percent of boys. These rates are down from previous years.

Incidents of tobacco use seem to peak between the ages of eighteen and twenty-five, when, according to the NSDUH, 40.8 percent of people report at least one experience with the product. The data clearly show that most Americans begin using tobacco products between the ages of twelve and twenty-five. It is this "target audience" that the anti-smoking campaigns seek to educate about the health dangers of tobacco. According to various anti-smoking organizations, it is this same group that smoking advertisements target.

Although the number of young smokers remains high, data from the 2004 Monitoring the Future (MTF) study show a slow but steady drop in the percentage of eighth-, tenth-, and twelfth-grade students who smoke cigarettes. Back in 1996, 21 percent of eighth graders, 30.4 percent of tenth graders, and 34 percent of twelfth graders had smoked during the month prior to the survey. Eight years later, in 2004, the figures had fallen to 9.2 percent of eighth graders, 16 percent of tenth graders, and 25 percent of twelfth graders reporting past-month cigarette usage. Teens who said they smoked more than a half a pack of cigarettes daily fell significantly over the eight-year span as well. In addition, according to MTF survey authors, "the perception of harm from smoking one or more packs per day increased significantly among eighth- and tenth-graders from 2003 to 2004."

Ties to Social Problems?

The various surveys show another fact as well. According to the American Heart Association, people with a high school education or less are three times more likely to be smokers than those with a college education. The prevalence of cigarette smoking is highest among people living below the poverty level, with one in three reporting tobacco use.

Charley, the Addicted Chimp

According to First Coast News in April of 2005, Charley, a resident of the Bloemfontein Zoo in South Africa, picked up a smoking habit after finding a pack of cigarettes thrown into his cage. Helpful zoo visitors lit his cigarettes for him. Charley learned to hide his cigarettes from the zookeepers, who would take them from him. The zoo staff feared he had become addicted. They posted signs asking visitors not to give Charley any more tobacco for fear that it was damaging his health.

A study of more than 4,000 students in Oregon and California linked early smoking with problem behaviors. Kids who start smoking around age twelve are considered "early smokers." In an article published in the Journal of Adolescent Health, Phyllis L. Ellickson and her coauthors reached the following conclusion: "Compared with nonsmokers, early smokers were at least three times more likely by grade twelve to regularly use tobacco and marijuana, use hard drugs, [and] drop out of school." In addition, these adolescents were "at higher risk for low academic achievement and behavioral problems at school."

Effects on the Body

Nicotine is the addictive compound in tobacco. When it enters the bloodstream, either through the lungs, the skin inside the mouth, or the nasal passages, it moves to the brain. There it binds with acetylcho-line receptors, triggering the release of other neurotransmitters and hormones. Basically, nicotine causes two sensations: stimulation in the thought processes, and general relaxation in the user.

The Need for a Cigarette

The quick-acting nicotine increases the amount of dopamine in the brain. This causes pleasure and relaxation of muscles. At the same time, it enhances norepinephrine and acetylcholine levels, increasing mental stimulation and suppressing appetite. Nicotine also enhances memory and promotes a feeling of well-being. In other words, the drug stimulates the brain's reward system, making the user "feel good."

When people say that cigarettes help them to concentrate, they are not exaggerating. Nicotine does have that effect. However, the effect wears off quickly unless another dose of nicotine enters the brain. Likewise, nicotine does cause a feeling of relaxation, but this too passes quickly, leading to a craving for more of the drug. Many behaviors are related to the addicting qualities of nicotine. The user, taking a puff on a cigarette, might just feel more relaxed because withdrawal symptoms have been held at bay for another hour.

A Dangerous Habit

Nicotine causes a release of epinephrine, leading to a faster heartbeat, higher blood pressure, quickened breathing, and higher blood sugar. So while the user may feel relaxed, the body is actually working harder to pump blood and take in oxygen. Over a long period of time, this strain on the heart and elevated blood pressure can lead to heart attack and stroke. The drug also complicates the chemistry of the blood, causing blood vessels to become smaller and blood cells to stick together in clots. This can increase the risk of organ damage and stroke. Over time, nicotine contributes to the build-up of plaque in the arteries, a leading cause of heart disease. The chemicals in cigarette smoke also irritate the throat, interfere with the lung's ability to clear debris and bacteria, and promote nausea and other digestive disturbances.

Most scientists agree that nicotine is the most addictive substance used by humankind—worse than cocaine, although it works in a similar way on the brain's reward centers. (An entry for

cocaine is available in this encyclopedia.) Because nicotine works so quickly and exits the brain just as quickly, it begins to induce cravings in most users within days or weeks of first use. Its effects are particularly strong on those with attention-deficit/hyperactivity disorder (ADHD), for whom it may be calming, and those with depression or a tendency to become depressed. People with those problems have a harder time freeing themselves from a nicotine addiction, so they are advised not to use tobacco at all.

Getting Hooked

Regular tobacco use causes tolerance, a condition that can lead to heavy smoking or chewing, and to lifestyle changes based on that heavy use. People find themselves spending a great deal of money on tobacco products, using them recklessly (smoking in bed, smoking while driving), and endangering the health of others with secondhand smoke.

At overdose levels, nicotine causes dizziness, vomiting, muscle tremors, convulsions, and paralysis of the lungs leading to an inability to breathe. All of these symptoms can develop within minutes. Tobacco products should be kept out of reach of children and pets. Those using nicotine replacement products should never smoke or chew tobacco at the same time. In addition, great care should be taken with any insecticide or other product containing pure nicotine.

The immediate effects of nicotine are generally mild and pleasurable; the long-term effects of tobacco use are not. Smokers accumulate a huge buildup of tar in the lungs, promoting cancer and clogging the air sacs that transfer oxygen into the bloodstream. The cancer-causing chemicals in tobacco promote growth of tumors in the mouth, on the lips, in the throat, in the lungs, in the esophagus, and elsewhere in the body. Nearly one in five deaths due to heart disease can be blamed on tobacco, and the overall death rate from cancer is twice as high among smokers as among nonsmokers.

More Dangers

People who smoke damage tiny, hair-like structures called cilia that lead to the lungs. Cilia help to remove germs and dirt from the lungs. This leads to an accumulation of mucus in the lungs and bronchial tubes—the famous "smoker's cough." Smokers also suffer more frequent and more serious cases of flu and pneumonia. Heavy tobacco use can cause men to become impotent and their sperm counts to decrease. Tobacco use has also been linked to cancers in the female reproductive organs.

Perhaps the most dangerous aspect of nicotine is the time it takes for the deadly side effects to develop. Most people begin using tobacco as teenagers, a time when they are most vulnerable to peer pressure and subtle advertising techniques. The vast majority of teenagers are enjoying the best health they will ever have in their lives. They cannot imagine growing old, developing health problems, or being at risk for fatal diseases. By the time they begin to understand how fragile the body is, they can already be deeply dependent on nicotine.

Becoming free of nicotine addiction causes immediate and long-term health benefits, including improved breathing, better sensation of taste, healthier teeth and skin, and improved strength. Quitting smoking also lessens the risks of cancer—but not entirely. Sometimes people who have not smoked in years discover that they have lung cancer. The disease is difficult to diagnose in its early stages. The very best way to avoid nicotine-related illnesses is to avoid any use of nicotine at any stage of life. If nicotine use has begun, the sooner it ends, the better the chances of living a long and healthy life.

Reactions with Other Drugs or Substances

Tobacco use causes the liver to produce more enzymes that can lower the blood levels of other medicines. Doctors should alter the doses of prescription drugs and monitor patients more carefully if those patients are using tobacco or nicotine replacement products. Nicotine should not be combined with certain asthma drugs, blood thinners, antipsychotic drugs, drugs for migraine headaches, and some antidepressants. Nicotine also interferes with some blood pressure medications such as Procardia and Tenormin. Women who are using birth control pills are urged not to smoke, because the combination of the pills and the tobacco can increase the likelihood of blood clots.

Any combination of nicotine and cocaine, opiates, hallucinogens, or marijuana can heighten the effects of the illegal drugs and possibly lead to irregular heartbeat or breathing problems. Heavy use of tobacco and alcohol further increases cancer risks. (Entries on alcohol and marijuana are available in this encyclopedia.)

Treatment for Habitual Users

Giving up the nicotine habit can be very difficult. Within hours of the last cigarette or chew, the body begins to respond to the lack of the drug. People become irritable and anxious, they overeat, they cannot sleep, and they can experience muscle tremors and a craving for tobacco. Many times, it is just easier to get another cigarette rather than to face the withdrawal symptoms.

Many self-help groups, including Nicotine Anonymous, the American Lung Association, the American Cancer Society, and the National Cancer Institute, have smoking cessation, or stopping, programs. Local- and state-funded programs also provide counselors and various treatment methods to the motivated addict who wants to quit using tobacco. These treatment programs may use hypnosis, group therapy, or behavior modification to encourage alternate behavior and help individuals combat the many facets of nicotine addiction. In many cases, health insurance companies will help pay for nicotine treatment programs.

Nicotine Withdrawal Symptoms

Nicotine withdrawal causes a variety of symptoms, including:

• restlessness
• anxiety
• impatience
• anger
• difficulty concentrating
• increased appetite and weight gain
• depression
• loss of energy and interest in life
• dizziness
• headache
• sweating
• insomnia, the inability to sleep
• tremors, shaking of limbs
• tightening of muscles
• cravings for tobacco.

Probably the most successful treatment methods involve nicotine replacement products such as gum (Nicorette) and skin patches (NicoDerm CQ, Nicotrol, Habitrol, and ProStep). These products recommend that the user work closely with a doctor or therapist to taper the doses of nicotine slowly. People using nicotine replacement therapies must take care not to use tobacco products at the same time, since this may lead to nicotine overdose. They must also be aware that these therapies can be habit-forming themselves, so they must be motivated not to exceed the recommended dose on the label of the package.

Other prescription drugs used to curb nicotine abuse include buproprion (Zyban), an antidepressant, and Clonidine (Catapres), a medicine to reduce high blood pressure. Both of these products block nicotine's pleasurable effects and help a recovering user avoid tobacco products.

For most, the best way to treat a tobacco habit is to combine a nicotine replacement therapy with counseling, education, group support, and the encouragement of family and friends. A heavy tobacco user must expect that the process will not always go smoothly and must have strategies in place for times of stress. Recovering nicotine addicts usually need to alter their lifestyles in order to avoid the people and places associated with smoking. If other family members smoke in the home, this can be very challenging.

The least effective way to attempt to quit nicotine is to depend on will power or to attempt to cut back on smoking by using low-tar cigarettes or by smoking less. People who try to quit in this way usually compensate by drawing more deeply on the cigarettes they do smoke. The relapse rate for this type of cessation is very high.

Consequences

Nicotine erodes health slowly at first. Most people begin smoking early in life, when they are enjoying the best health they will ever have. Gradually, however, the consequences of long-term tobacco use become evident. People suffer from bad breath, discolored teeth, cravings, and dryness and thinning of the skin. They may develop a "smoker's cough" or a gravelly voice from damage to the larynx, the organ that produces sound in the throat. They may develop lesions—sores that do not heal or that heal very slowly—on their lips or inside the mouth. All of these are early warning signs of trouble to come.

Kreteks and Bidis

Kreteks are clove-spiced cigarettes from Indonesia. Bidis are small, flavored cigarettes from India. Both are available on the American market, and both contain high concentrations of nicotine—higher, even, than American cigarettes. These items are tobacco products, and they are habit-forming.

Increased Risk of Cancer and Other Illnesses

It is estimated that one-third of all cancers and 87 percent of lung cancer in the United States can be traced directly to tobacco use. Cancer

is an illness in which cells grow and reproduce too quickly, causing tumors inside the body. The tumors can be small at first and then grow rapidly. If the cancer reaches the lymph glands that send hormones throughout the body, the cancer can spread through the body as well. Cancer treatment generally involves surgery to remove tumors. Surgery is often followed by chemotherapy, a process that shrinks tumors but also causes nausea, weakness, hair loss, and malfunction of the immune system. Some tumors are treated with radiation to stem their growth. Radiation can cause pain and burning of the skin.

Cancer is treatable, but smokers are twice as likely to die of it as nonsmokers diagnosed with the same illness. Heavy smokers are four times more likely to die of their cancers as nonsmokers diagnosed with similar cancers.

Long-term tobacco use is directly linked to heart attack, various lung illnesses, high blood pressure, and stomach ulcers. It also reduces the body's ability to heal broken bones, promotes arthritis, and causes bad breath and yellowing of the teeth. All of these effects stem from a product that is legal for use in the American adult population. However, the U.S. Surgeon General's warning about the various health consequences of smoking appears on all packs of cigarettes sold in the United States.

The Law

In most states, people must be eighteen years old to purchase tobacco products legally. In Alabama, Alaska, and Utah, the minimum age for purchase of tobacco is nineteen. As of the early 2000s, four other states—California, New Jersey, Illinois, and Massachusetts—were considering laws to raise the age as well. The burden of keeping underage persons from buying cigarettes or smokeless tobacco falls on the stores that sell it.

Shopkeepers risk prosecution if they are caught selling tobacco to minors. Most stores require that younger buyers produce valid identification showing date of birth. Occasionally, young undercover police officers will attempt to buy tobacco without proper identification to see if the shopkeepers are abiding by the law. A store owner who sells tobacco to a minor risks losing his or her license to sell the product, as well as fines or closure of the business.

People under the age of eighteen who get caught with tobacco products do not face criminal prosecution. However, they can be suspended from school if caught with tobacco on school grounds. Most authorities contact parents or legal guardians to report the situation. For teens who smoke, secrecy rarely lasts very long. The telltale smell of tobacco clinging to clothing and hair is hard to disguise.

Discrimination Against Smokers

In some states, private companies have introduced policies that deny jobs to smokers. The companies cite the extra burden of health care costs for their smoking employees, as well as loss of work time due to smoking breaks. Many smokers claim that this is discrimination and should not be a factor deciding employment, especially since smoking is legal. As of early 2005 no lawsuits had yet developed from the introduction of these measures, but analysts expected that legal action would soon occur.

Various states have laws that prohibit employers from discriminating against their staff for engaging in certain legal activities, like smoking, while they are not at work. According to Marshall H. Tanick in the Minneapolis Star Tribune "about two dozen states … have so-called 'lifestyle rights' laws," including Minnesota, Texas, California, and Florida. Such laws prohibit employers from discriminating against "employees because of lawful off-duty conduct." Tanick noted that the 1992 Minnesota law specifically "extends to consumption of 'food, alcohol, or non-alcoholic beverages and tobacco."' Employers can restrict the use of certain products, consumed by the employee off-duty, if use of those products interferes with the person's ability to do his or her job.

For More Information

Books

Balkin, Karen F. Tobacco and Smoking. San Diego, CA: Greenhaven Press, 2005.

Brigham, Janet. Dying to Quit: Why We Smoke and How We Stop. Washington, DC: Joseph Henry Press, 1998.

Gahlinger, Paul M. Illegal Drugs: A Complete Guide to Their History, Chemistry, Use and Abuse. Las Vegas, NV: Sagebrush Press, 2001.

Haugen, Hayley Mitchell. Teen Smoking. San Diego, CA: Greenhaven Press, 2004.

Kuhn, Cynthia, Scott Swartzwelder, and Wilkie Wilson. Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy, 2nd ed. New York: W.W. Norton, 2003.

McCay, William. The Truth about Smoking. New York: Facts on File, 2005.

Wagner, Heather Lehr. Nicotine. Philadelphia: Chelsea House, 2003.

Whelan, Elizabeth M. Cigarettes: What the Warning Label Doesn't Tell You: The First Comprehensive Guide to the Health Consequences of Smoking. Amherst, NY: Prometheus Books, 1997.

Periodicals

"AMA Wants 'R' Rating for Movies with Smoking." Tobacco Retailer (August, 2004): p. 13.

Ellickson, Phyllis L., Joan S. Tucker, and David J. Klein. "High-Risk Behaviors Associated with Early Smoking: Results from a Five-Year Follow-Up." Journal of Adolescent Health (June, 2001).

"Fired for Smoking?: Michigan Health Care Company Has Strict Anti-Tobacco Policy." Associated Press (January 26, 2005).

Grunbaum, Jo Anne, and others. "Youth Risk Behavior Surveillance: United States, 2001." Journal of School Health (October, 2002): p. 313.

Holcomb, Betty. "The Winner." Good Housekeeping (July, 1999): p. 27.

Kowalski, Kathiann M. "How Tobacco Ads Target Teens." Current Health 2 (April-May, 2002): p. 6.

"Silver Screen Smoking Is on the Rise." USA Today Magazine (November, 2003): p. 9.

Springer, Karen. "Smoking: Light Up and You May Be Let Go." Newsweek (February 7, 2005): p. 10.

Susman, Ed. "Doctors Seek 'R' for Smoking in Movies." UPI Perspectives (June 14, 2004).

Worth, Robert. "Making It Uncool." Washington Monthly (March, 1999): p. 8.

Web Sites

"2003 National Survey on Drug Use and Health (NSDUH)." U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration.http://www.oas.samhsa.gov/nhsda.htm (accessed July 30, 2005).

Billingsley, Janice. "Anti-Tobacco Programs Cut Teen Smoking Rates." Forbes.com, January 28, 2005. http://www.forbes.com/lifestyle/health/feeds/hscout/2005/01/28/hscout523634.html (accessed July 30, 2005).

"Campaign for Tobacco-Free Kids." Tobacco-Free Kids.http://www.tobaccofreekids.org (accessed July 30, 2005).

"Chimps Hooked on Smoking." First Coast News, April 22, 2005. http://www.firstcoastnews.com/news/strange/news-article.aspx?storyid=35962 (accessed July 31, 2005).

"Cigarette Smoking among American Teens Continues to Decline, but More Slowly than in the Past." National Institute of Drug Abuse.http://www.nida.nih.gov/DrugPages/MTF.html (accessed July 30, 2005).

"Cigarette Smoking Statistics." American Heart Association.http://www.americanheart.org/presenter.jhtml?identifier=4559 (accessed July 30, 2005).

Huggins, Charnicia E. "Lung Cancer No Longer Just a Man's Disease." Yahoo! News.http://news.yahoo.com (accessed June 8, 2005).

"Kicking the Habit Can Add Years to Your Life." MSNBC.com, February 14, 2005. http://www.msnbc.msn.com/id/6969860 (accessed July 30, 2005).

"Molecule May Be Key to Nicotine Addiction." MSNBC.com, November 4, 2004. http://msnbc.msn.com/id/6405269 (accessed July 30, 2005).

Monitoring the Future.http://www.monitoringthefuture.org/ and http://www.nida.nih.gov/Newsroom/04/2004MTFDrug.pdf (both accessed August 31, 2005).

National Institute on Drug Abuse.http://www.nida.nih.gov and http://www.drugabuse.gov (both accessed July 30, 2005).

"One Puff of Smoke Can Damage DNA." MSNBC.com, October 1, 2004. http://www.msnbc.msn.com/id/6152449/ (accessed July 30, 2005).

"Smoking Killed 5 Million Worldwide in 2000." MSNBC.com, November 24, 2005. http://www.msnbc.msn.com/id/6574849/ (accessed July 30, 2005).

"Study: Smoking Harms Women More than Men." Yahoo! News.http://news.yahoo.com (accessed June 28, 2005).

Tanick, Marshall H. "Clearing the Air in the Workplace." Star Tribune, April 3, 2005. www.startribune.com/stories/535/5323366.html (accessed August 1, 2005).

"Tobacco Information and Prevention Source (TIPS)." Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion.http://www.cdc.gov/tobacco/issue.htm (accessed July 30, 2005).

See also: Alcohol; Cocaine; Marijuana

Nicotine

At the beginning of the twentieth century, lung cancer was a rare medical disease. The "cigarette," a new product, was becoming popular among the wealthy and trendsetters, while in England, Professor John N. Langley of Cambridge University was exploring the effects of nicotine, a powerful chemical and effective pesticide extracted from tobacco. It was known that nicotine could be absorbed through the skin, causing sickness in humans. Understanding of how the brain and nervous system work (called "neuroscience" today) was just emerging at the beginning of the century. Little was known about the functioning of the brain or how it sent messages through the body's network of nerve fibers to move muscles or stimulate the heart, or how these nerves transmitted information to the brain. Nicotine would become one of the chemicals used to help unravel these mysteries and jumpstart the field of neurophysiology.

By the end of the twentieth century, a groundswell of scientific research had transformed our understanding of nicotine from being an obscure poison to being an addicting drug responsible for taking millions of tobacco smokers to premature death. Many secrets of the brain and nervous system were also unraveled through the help of nicotine, because nicotine has profound effects on parts of the nervous system (now termed "nicotinic"). Thus, nicotine emerged as a vital laboratory tool in understanding the functioning of the nervous system. From the standpoint of public health, one of the most striking features in the history of nicotine science was the recognition that nicotine was an addicting drug, and that tobacco addiction was among the deadliest addictions in the world. Nearly one-half of daily smokers would die prematurely of tobacco-attributed diseases—primarily cancer, lung, and cardiovascular diseases.

What led to the development and understanding of nicotine as a deadly drug? How does nicotine affect the nervous system, and what role does it play in tobacco use? These are some of the vexing questions that scientists around the world grappled with as they learned about nicotine and its effects on the body.

History of Nicotine

Nicotine derives its name from Jean Nicot, a French ambassador to the Portuguese court from 1559 to 1561. The story is that the thirty-yearold diplomat paid a visit to a famous Portuguese horticulturalist, Damiao de Goes, who gave him leaves from a strange plant reputed to have marvelous effects. Nicot dried the leaves, crushed them, and sent the powder back to the queen mother Catherine de Medici, who suffered from severe headaches. Reportedly, the remedy worked, and the tobacco plant quickly gained popularity in France, making Nicot something of a celebrity. The plant came to be called the Herb of Nicot.

But it was not until the nineteenth century that the chemical nicotine was identified as a distinct ingredient in tobacco. In 1809, Louis Nicolas Vauquelin (a French chemist) extracted a "potent, volatile, and colorless substance" from tobacco which he named essence de tabac, though it was not pure nicotine that was derived. In 1828 two chemistry students at the University of Heidelberg, Ludwig Reimann and Wilhelm Heinrich Posselt, first isolated nicotine, which they named after Nicot, as the active ingredient in tobacco.

In 1905, John Newport Langley, a British physiologist, discovered that a miniscule drop of nicotine stimulated muscle fibers while a similar amount of another poison, curare, paralyzed them when administered simultaneously to anesthetized birds. Langley correctly concluded that muscles and nerves must contain what he termed "receptive substances" (now called "receptors"). In response to different chemicals, these receptors were either activated or deactivated. Drugs that activate receptors are called "agonists." For example, the deadly poison, curare, exerted its lethal paralysis of muscles, including those working the lungs, by blocking nicotinic receptors. But the right dose of nicotine could reactivate muscles depressed by curare. Nicotine was one of a particularly interesting type of chemicals in which a small amount (called the "dose") could produce activation while a larger dose could produce deactivation. In other words, the strength of nicotine's effects was closely related to the dose administered and repeated dosing led to weaker effects (or tolerance). These discoveries helped to explain how muscles could be stimulated or relaxed by the same nerve. By the end of the twentieth century, thousands more of the body's receptor types and subtypes had been identified, helping to explain many aspects of physical, behavioral, and cognitive functioning. This led to the discovery of medicines for treating hundreds of diseases.

Nicotine's Effect on the Body

Nicotine is the cerebrally acting drug in tobacco that defines its addicting effects, similar to the way cocaine in the coca leaf and morphine in the opium poppy define the addictive effects of those substances. Nicotine affects the brain by binding to specific receptors (called nicotine cholinergic receptors) on the surface of brain cells. This stimulates the cells to release neurotransmitters such as epinephrine and dopamine. Epinephrine provides the fast "kick" to the smoker, causing a release of glucose and an increase in heart rate, blood pressure, and breathing. Dopamine is fundamental to reward and pleasure pathways in the brain and is boosted by other addictive drugs, such as cocaine and heroin, as well as by nicotine.

Nicotine produces an entire range of physical and behavioral effects characteristic of addicting drugs. These effects include activation of brain reward systems (creating behavioral effects and physiological cravings that lead to chronic drug use), tolerance and physical dependence, and withdrawal with drug abstinence. Nicotine alters a person's mood, feelings, and behavior, and its effects can be complicated. At very high doses, the effects of nicotine on heart rate and blood pressure can be dangerous, even fatal, but there is no conclusive evidence that modest doses of nicotine—like those received from a nicotine patch—are detrimental to health.

The fast action of inhaled nicotine makes cigarette smoking the most addictive route for administering nicotine, which reaches the smoker's brain less than 10 seconds after inhalation. Because inhaled nicotine reaches the bloodstream so quickly, it produces an intense but short-lived spike in its levels. In contrast, nicotine from a skin patch works its way into the bloodstream slowly, over about three hours, and never reaches the peak levels that inhaled nicotine does, even when the overall dose is the same (nicotine nasal spray and nicotine chewing gum fall somewhere in the middle). Not surprisingly, smokers report that their habit is highly reinforcing (they want to keep repeating the experience), but they do not show the same enthusiasm for the nicotine patch.

Nicotine dependence is far more common than cocaine, heroin, or alcohol dependence following initial use of these drugs. Approximately one-third to one-half of those who try smoking increase to more regular or daily use, and most daily smokers become addicted. In contrast, less than one in four persons who try cocaine or heroin develop addiction, and less than 15 percent of alcohol users develop addiction. Nicotine, alone and in combination with other substances, appears to help regular smokers control their mood and body weight and maintain attention when working. Daily smokers will claim that they function best on nicotine. Even a brief period of tobacco abstinence can leave some addicted individuals unable to complete their office- or schoolwork, or to perform adequately.

Tobacco Product Design

Nicotine accounts for approximately 1–4 percent of the weight of a typical tobacco leaf, which is transferred into the bloodstream by chewing products made for oral use or by inhaling the smoke of burning tobacco. Tobacco products can be viewed as nicotine storage and delivery systems. The tobacco industry has used a variety of techniques to enhance the delivery of nicotine to the user by controlling the nicotine dosing characteristics of cigarettes and other products. The modern cigarette is intricately designed, involving numerous patents for cigarette wrappers, filter systems, and processes for making "tobacco filler" from tobacco materials and other substances. William Dunn, a senior Philip Morris scientist, has eloquently described the cigarette's function:

The cigarette should be conceived not as a product but as a package. The product is nicotine. Think of the cigarette as a dispenser for a dose unit of nicotine. . . . Think of a puff of smoke as the vehicle of nicotine. Smoke is beyond question the most optimized vehicle of nicotine and the cigarette the most optimized dispenser of smoke

(CAMPAIGN FOR TOBACCO-FREE KIDS 1998,
CITED IN HURT AND ROBERTSON).

Tobacco is a complex "cocktail" of more than 4,000 distinct chemical substances, some of which can interact to increase the addicting effects of tobacco-delivered nicotine, far above those produced by nicotine alone. For example, buffering compounds in smokeless tobacco products can alter the speed and amount of nicotine delivered in those products. The addition of menthol apparently allows smokers to inhale larger quantities of smoke, and nicotine, by making them feel less harsh. Techniques are also employed to control the size of smoke particles allowing the efficient inhalation of nicotine deep into the lungs where absorption is rapid and virtually complete. Among the many chemicals in tobacco smoke, scientists are only now beginning to unravel the many individual chemicals and their combinations that bolster the addictive effects of tobacco.

Nicotine Addiction "Drives" Smoking Behavior

While early antitobacco campaigns warned that cigarette smoking could be habit forming, drawing parallels with narcotics, it was not until the 1980s that leading scientists and health organizations recognized cigarettes to be addicting. The 1988 United States Surgeon General's report focused on the role of nicotine in smoking and concluded that "Cigarettes and other forms of tobacco are addicting," "Nicotine is the drug in tobacco that causes addiction," and "The pharmacologic and behavioral processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine."

Smokers become very adept at getting the dose that provides the desired effects. This is associated with a phenomenon known as "tolerance," which refers to increasing the amount of drug to experience the same effects once received at lower doses. When tolerance develops and tobacco intake increases, a person typically becomes physiologically dependent. Quitting is accompanied by withdrawal symptoms, including impaired concentration, irritability, weight gain, depressed mood, anxiety, difficulty sleeping, and persistent craving for a cigarette. During withdrawal, resumption of smoking provides rapid relief of withdrawal effects, leading the smoker to believe that smoking is a mood and performance-enhancing substance. However, resumption of smoking prevents withdrawal that occurs because physical dependence results from daily use of tobacco. Although there is individual variation, withdrawal usually peaks within a few days and subsides within a month.

Nicotine and Public Health

The World Health Organization, the United States Public Health Service, and most major health organizations worldwide endorsed efforts to make tobacco abstinence a major health priority by the end of the twentieth century. The overwhelming weight of scientific study has shown that quitting smoking at virtually any age results in a reduced disease risk and better health outcomes if tobacco-attributed disease has already developed. The results of smoking cessation are quite dramatic. For example, the risk of heart disease—the leading cause of death among smokers—is reduced nearly to that of nonsmokers within one to two years of cessation.

Preventing the development of tobacco addiction is vital to the long-term health of generations to come. But the road to longer and healthier lives is in cessation for today's 50 million cigarette smokers in the United States and more than 1.2 billion smokers worldwide. Therefore, major governments and health organizations have launched important initiatives to motivate people to quit smoking. In recognition of the power of addiction and the need for people to quit, these organizations have also made smoking cessation treatments more accessible. Many people can now receive medical assistance to achieve freedom from tobacco by contacting the public health service of their nation, cancer institutes, the World Health Organization, and various voluntary organizations such as local cancer societies and lung health organizations.

See Also Addiction; Genetic Modification; "Light" and Filtered Cigarettes; Toxins.

▌ PATRICIA B. SANTORA
▌ JACK E. HENNINGFIELD

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United States Department of Health and Human Services. The Health Consequences of Smoking: Nicotine Addiction. A Report of the Surgeon General. Washington, D.C.: United States Government Printing Office, 1988.

——. Reducing Tobacco Use: A Report of the Surgeon General. Rockville, Md.: Department of Health and Human Services, United States Public Health Service, 2000.

United States Department of Health, Education, and Welfare. Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service. Public Health Publication No. 1103. Washington, D.C.: United States Government Printing Office, 1964.

World Health Organization, Tobacco Free Initiative. Available: <http://www.who.int/tobacco/en>.

opium an addictive narcotic drug produced from poppies. Derivatives include heroin, morphine, and codeine.

epinephrine also called adrenaline, a chemical secretion of the adrenal gland. Epinephrine speeds the heart rate and respiration.

dopamine a chemical in the brain associated with pleasure and well-being. Nicotine raises dopamine levels and intensifies addiction to cigarette smoking.

physiology the study of the functions and processes of the body.

menthol a form of alcohol imparting a mint flavor to some cigarettes.

Nicotine

Nicotine is a colorless, oily, acrid (bitter, pungent) liquid with the chemical formula C₁₀H₁₄N₂. It is an alkaloid found primarily in leaves of the tobacco plant (Nicotiana tabacum ). While the tobacco plant is indigeous to North America, it is now commercially cultivated and naturalized in most subtropical countries. The word nicotine comes from Jean Nicot (1530–1600), a French diplomat and scholar, who introduced tobacco to France in the sixteenth century.

Many societies throughout the world have prized nicotine for its mood-altering properties. Although it is a stimulant, it can produce either relaxation or arousal, depending on the user’s state (the relaxation appears occur on a muscular level). Users commonly burn the leaves and inhale the smoke; some, however, may chew the leaves, while others snuff finely ground leaves into their noses or place them between their cheeks and gums.

Nicotine is so highly addictive that the American Psychiatric Association includes it in their diagnostic manual under substance dependence. Nicotine addiction is also very difficult to break—only 5% of those who attempt to quit smoking are successful on their first try, and only 3% can kick the habit for a whole year. Only 10% of smokers are not addicted. To relieve the physical and psychological symptoms of nicotine withdrawal—restlessness, anxiety, irritability, depression, difficulty in concentrating, and a craving for the drug—pharmaceutical companies now offer nicotine replacement systems such as the nicotine patch and gum. These systems deliver nicotine in a less addicting pattern that allows the dose to be gradually decreased and eventually eliminated. Even with nicotine replacement, however, successful quitting requires determination and is more successful when psychological support—like those offered in kicking other addictive substances—is given. Two drugs—clonidine, and the antidepressant bupropion (Wellbrutin^®)—have been approved by the Food and Drug Administration (FDA) to help people quit.

Like most alkaloids, nicotine exerts its effects at receptors for chemicals that transmit nerve impulses. Specifically, nicotine acts at the nicotinic receptor class for the transmitter acetylcholine (the other class of acetylcholine receptor is the muscarinic, also named for a compound—a mushroom derivative—that triggers only receptors of that class). Outside the brain, nicotinic receptors are found primarily in the sympathetic nervous system, while muscarinic receptors are found in the parasympathetic nervous system. Thus, nicotine use triggers sympathetic nervous system effects throughout the body.

These effects largely account for nicotine’s unfavorable impact on the user’s health. People pay a great deal of attention to the danger of lung cancer, which results when smokers inhale cigarette smoke. While nicotine in itself is not carcinogenic, cigarettes and tobacco products contain more than 4,000 different chemicals, 60 of which are known carcinogens, and account for approximately one in every seven deaths in the United States, and one in three between the ages of 35 and 70 years—primarily due tocancers and cardiovascular diseases. Nicotine does, however, constrict small arteries, which raises the blood-pressure and makes the heart work harder. It also makes the heart beat faster, yet, because it constricts the arteries supplying the heart muscle, the organ receives less blood. When buildups of fatty plaque have already narrowed heart arteries, this may be enough to trigger heart pain (angina) or heart attack. In addition, elevated blood pressure greatly increases the risk of stroke. Nicotine causes circulatory problems, particularly affecting the hands and feet, and causes some men difficulty in obtaining an erection.

On the other hand, nicotine may have beneficial properties: for some users, it inhibits the appetite and slightly speeds up the body’s metabolic rate, helping to keep weight down. In addition, research has shown smokers appear to have a decreased risk of Parkinson disease.

Nicotine is also used as an insecticide to control aphids. In such applications, the nicotine is extracted from the stem and the leaf mid ribs of tobacco plants (those sections not used in the manufacture of smoking tobacco) and distilled. Nicotine is a strong, fast acting poison and it is usually applied as a 0.5% solution in water.

In 1992, the Surgeon General of the United States declared nicotine to be as addictive as cocaine. An article published in the December 17, 1997 issue of the Journal of the National Cancer Institute stated nicotine addiction rates are higher than for alcohol or cocaine.

The World Health Organization (WHO) has named tobacco, which contains nicotine, one of the greatest public health threats of the twenty-first century. The U.S. Centers for Disease Control and Prevention (CDC) has declared that tobacco use is most preventable risk to human health in developed countries. As of 2004, over one billion people worldwide smoke. More than 3.5 million people are expected to die annually from causes directly related to tobacco use. This death rate is expected to rise to 10 million by the year 2030.

Nicotine

OVERVIEW

Nicotine (NIK-uh-teen) is a thick, colorless to yellow, oily liquid with a bitter taste that turns brown when exposed to air. It occurs in high concentrations in the leaves of tobacco plants and in lower concentrations in tomatoes, potatoes, eggplants, and green peppers. Nicotine gets its name from the tobacco plant, Nicotiana tabacum, which, in turn, was named in honor of the French diplomat and scholar Jean Nicot (1530–1600), who introduced the use of tobacco to Paris. Nicotine's correct chemical structure was determined in 1843 by the Belgian chemist and physicist Louise Melsens (1814–1886) and the compound was first synthesized by the research team of A. Pictet and A. Rotschy in 1904.

KEY FACTS

OTHER NAMES:

r(S)-3-(1-methyl-2-pyrrolidinyl)pyridine; 1-methyl-2-(3-pyridyl)-pyrrolidine

FORMULA:

C₅H₄NC₄H₇NCH₃

ELEMENTS:

Carbon, hydrogen, nitrogen

COMPOUND TYPE:

Alkaloid (organic)

STATE:

Liquid

MOLECULAR WEIGHT:

162.23 g/mol

MELTING POINT:

−79°C (−110°F)

BOILING POINT:

247°C (477°F)

SOLUBILITY:

Miscible with water; very soluble in ethyl alcohol, ether, and chloroform

HOW IT IS MADE

Nicotine is extracted by soaking the stems and leaves of the tobacco plant in water for about twelve hours. After that period of time, the nicotine in the tobacco has dissolved in the water and can be extracted in a variety of ways. In one process, the water solution of nicotine is mixed with ether or chloroform, in which the nicotine is more soluble. The nicotine moves from the water layer to the ether or chloroform layer, from which it can be removed by evaporation.

COMMON USES AND POTENTIAL HAZARDS

The best-known application of nicotine is in tobacco products used for smoking and chewing. The actual nicotine content of tobacco products varies considerably, but, on average, ranges from about 15 to 25 milligrams per cigarette. Nicotine is also available in a number of products designed to help people stop smoking, such as nicotine gums and nicotine patches.

Nicotine was often used by farmers and gardeners as an insecticide and a fumigant in the past. Perhaps the best known of these in the United States was an insecticide known as Black Leaf 40, a 40 percent solution of nicotine sulfate in water. The use of Black Leaf 40 and most other nicotine-containing insecticides has, to a large extent, been discontinued because of the toxic nature of the compound. The risk it posed to human users was greater than its value as an agricultural product.

Nicotine is a highly addictive substance. For that reason, people have difficulty stopping smoking or chewing tobacco products even when they recognize the health hazards posed by the compound. Smokers depend on nicotine to give them a burst of energy, since it stimulates the heart rate and quickens blood flow. Once a person becomes addicted to the use of nicotine, it requires larger doses of the compound to produce comparable effects. A 1998 U.S. government report issued by then-Surgeon General C. Everett Koop found that the addictive properties of nicotine are comparable to those of heroin and cocaine.

Interesting Facts

• It takes only about seven seconds after nicotine is ingested before the chemical reaches the human brain.
• Nicotine is one of the most widely used addictive drugs in the United States.

When a person uses tobacco, nicotine is quickly absorbed through respiratory tissues, the skin, and the gastrointestinal tract. The actual amount of nicotine absorbed by the body depends on a number of factors, including the type of tobacco being smoked and the presence or absence of a filter on the cigarette. After entering the body, nicotine flows through the bloodstream and across the blood brain barrier. Levels of the stimulating hormone adrenaline increase, as do blood sugar levels, respiration rates, blood pressure, and heart rate. Nicotine can make small arteries constrict, putting strain on the heart and raising blood pressure. If a person already has clogged arteries, this effect may cause heart pain (angina) or a heart attack.

Although nicotine is a stimulant, it may induce muscle relaxation, depending on the user's physical state. It has also been shown to decrease one's appetite, speed up metabolism, and increase levels of dopamine, a mood-altering chemical in the brain that induces feelings of pleasure. Low levels of dopamine play a role in the development of Parkinson's disease. Research has shown that smokers, with higher levels of dopamine, have a reduced risk of the disease. Women who are pregnant are advised not to use any product containing nicotine. Nicotine in any form is harmful to an unborn child. It rapidly crosses the placenta and enters the fetus's body.

Nicotine is a highly toxic poison, which explains its former popularity as a pesticide. In high doses, it can be lethal. Low doses of nicotine can cause dizziness, nausea, and vomiting. Symptoms of acute nicotine poisoning may include a burning sensation in the mouth, more severe nausea and vomiting, diarrhea, heart palpitations, fluid in the lungs, seizures, coma, and death. People who smoke while receiving nicotine replacement therapy are at risk of nicotine poisoning.

Words to Know

MISCIBLE

Able to be mixed; especially applies to the mixing of one liquid with another.

NEUROTRANSMITTER

A chemical that carries nerve transmissions from one nerve cell to an adjacent nerve cell.

FOR FURTHER INFORMATION

"Acute Nicotine Poisoning." Mosby's Medical, Nursing, and Allied Health Dictionary. 5th edition. St. Louis: Mosby, 1998.

"Facts about Nicotine and Tobacco Products." National Institute on Drug Abuse. http://www.drugabuse.gov/NIDA_Notes/NNVol13N3/tearoff.html (accessed on October 20, 2005).

"Nicotine." International Labour Organization. http://www.ilo.org/public/english/protection/safework/cis/products/icsc/dtasht/_icsc05/icsc0519.htm (accessed on October 20, 2005).

"Nicotine (Black Leaf 40) Chemical Profile 4/85." Pesticide Management Education Program, Cornell University. http://pmep.cce.cornell.edu/profiles/insect-mite/mevinphos-propargite/nicotine/insect-prof-nicotine.html (accessed on October 20, 2005).