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What is Nicotine?

Nicotine, one of more than 4,000 chemicals found in the smoke from tobacco products such as cigarettes, cigars, and pipes, is the primary component in tobacco that acts on the brain. Smokeless tobaccoTobaccoPlant.gif (16234 bytes) products such as snuff and chewing tobacco also contain many toxins as well as high levels of nicotine. Nicotine, recognized as one of the most frequently used addictive drugs, is a naturally occurring colorless liquid that turns brown when burned and acquires the odor of tobacco when exposed to air. There are many species of tobacco plants; the tabacum species serves as the major source of tobacco products today. Since nicotine was first identified in the early 1800s, it has been studied extensively and shown to have a number of complex and sometimes unpredictable effects on the brain and the body.

Cigarette smoking is the most prevalent form of nicotine addiction in the United States. Most cigarettes in the U.S. market today contain 10 milligrams (mg) or more of nicotine. Through inhaling smoke, the average smoker takes in 1 to 2 mg nicotine per cigarette. There have been substantial increases in the sale and consumption of smokeless tobacco products also, and more recently, in cigar sales.

Nicotine is absorbed through the skin and mucosal lining of the mouth and nose or by inhalation in the lungs. Depending on how tobacco is taken, nicotine can reach peak levels in the bloodstream and brain rapidly. Cigarette smoking, for example, results in rapid distribution of nicotine throughout the body, reaching the brain within 10 seconds of inhalation. Cigar and pipe smokers, on the other hand, typically do not inhale the smoke, so nicotine is absorbed more slowly through the mucosal membranes of their mouths. Nicotine from smokeless tobacco also is absorbed through the mucosal membranes.

Is nicotine addictive?

Yes, nicotine is addictive. Most smokers use tobacco regularly because they are addicted to nicotine. Addiction is characterized by compulsive drug-seeking and use, even in the face of negative health consequences, and tobacco use certainly fits the description. It is well documented that most smokers identify tobacco as harmful and express a desire to reduce or stop using it, and nearly 35 million of them make a serious attempt to quit each year. Unfortunately, less than 7 percent of those who try to quit on their own achieve more than 1 year of abstinence; most relapse within a few days of attempting to quit.

Other factors to consider besides nicotine's addictive properties include its high level of availability, the small number of legal and social consequences of tobacco use, and the sophisticated marketing and advertising methods used by tobacco companies. These factors, combined with nicotine's addictive properties, often serve as determinants for first use and, ultimately, addiction. 

Recent research has shown in fine detail how nicotine acts on the brain to produce a number of behavioral effects. Of primary importance to its addictive nature are findings that nicotine activates the brain circuitry that regulates feelings of pleasure, the so-called reward pathways. A key brain chemical involved in mediating the desire to consume drugs is the neurotransmitter dopamine, and research has shown that nicotine increases the levels of dopamine in the reward circuits. Nicotine's pharmacokinetic properties have been found also to enhance its abuse potential. Cigarette smoking produces a rapid distribution of nicotine to the brain, with drug levels peaking within 10 seconds of inhalation. The acute effects of nicotine dissipate in a few minutes, causing the smoker to continue dosing frequently throughout the day to maintain the drug's pleasurable effects and prevent withdrawal.

What people frequently do not realize is that the cigarette is a very efficient and highly engineered drug-delivery system. By inhaling, the smoker can get nicotine to the brain very rapidly with every puff. A typical smoker will take 10 puffs on a cigarette over a period of 5 minutes that the cigarette is lit. Thus, a person who smokes about 1-1/2 packs (30 cigarettes) daily, gets 300 "hits" of nicotine to the brain each day. These factors contribute considerably to nicotine's highly addictive nature.

Scientific research is also beginning to show that nicotine may not be the only psychoactive ingredient in tobacco. Using advanced neuroimaging technology, scientists can see the dramatic effect of cigarette smoking on the brain and are finding a marked decrease in the levels of monoamineoxidase (MAO), an important enzyme that is responsible for breaking down dopamine. The change in MAO must be caused by some tobacco smoke ingredient other than nicotine, since we know that nicotine itself does not dramatically alter MAO levels. The decrease in two forms of MAO, A and B, then results in higher dopamine levels and may be another reason that smokers continue to smoke - to sustain the high dopamine levels that result in the desire for repeated drug use.

How does nicotine deliver its effect?

Nicotine can act as both a stimulant and a sedative. Immediately after exposure to nicotine, there is a "kick" caused in part by the drug's stimulation of the adrenal glands and resulting discharge of epinephrine (adrenaline). The rush of adrenaline stimulates the body and causes a sudden release of glucose as well as an increase in blood pressure, respiration, and heart rate. Nicotine also suppresses insulin output from the pancreas, which means that smokers are always slightly hyperglycemic. In addition, nicotine indirectly causes a release of dopamine in the brain regions that control pleasure and motivation. This reaction is similar to that seen with other drugs of abuse - such as cocaine and heroin - and it is thought to underlie the pleasurable sensations experienced by many smokers. In contrast, nicotine can also exert a sedative effect, depending on the level of the smoker's nervous system arousal and the dose of nicotine taken.

What happens when taken for a long time?

Chronic exposure to nicotine results in addiction. Research is just beginning to document all of the neurological changes that accompany the development and maintenance of nicotine addiction. The behavioral consequences of these changes are well documented, however. Greater than 90 percent of those smokers who try to quit without seeking treatment fail, with most relapsing within a week.

Repeated exposure to nicotine results in the development of tolerance, the condition in which higher doses of a drug are required to produce the same initial stimulation. Nicotine is metabolized fairly rapidly, disappearing from the body in a few hours. Therefore some tolerance is lost overnight, and smokers often report that the first cigarettes of the day are the strongest and/or the "best." As the day progresses, acute tolerance develops, and later cigarettes have less effect.

Cessation of nicotine use is followed by a withdrawal syndrome that may last a month or more; it includes symptoms that can quickly drive people back to tobacco use. Nicotine withdrawal symptoms include irritability, craving, cognitive and attentional deficits, sleep disturbances, and increased appetite and may begin within a few hours after the last cigarette. Symptoms peak within the first few days and may subside within a few weeks. For some people, however, symptoms may persist for months or longer.

An important but poorly understood component of the nicotine withdrawal syndrome is craving, an urge for nicotine that has been described as a major obstacle to successful abstinence. High levels of craving for tobacco may persist for 6 months or longer. While the withdrawal syndrome is related to the pharmacological effects of nicotine, many behavioral factors also can affect the severity of withdrawal symptoms. For some people, the feel, smell, and sight of a cigarette and the ritual of obtaining, handling, lighting, and smoking the cigarette are all associated with the pleasurable effects of smoking and can make withdrawal or craving worse. While nicotine gum and patches may alleviate the pharmacological aspects of withdrawal, cravings often persist.

Medical consequences

The medical consequences of nicotine exposure result from effects of both the nicotine itself and how it is taken. The most deleterious effects of nicotine addiction are the result of tobacco use, which accounts for one-third of all cancers. Foremost among the cancers caused by tobacco is lung cancer - the number one cancer killer of both men and women. Cigarette smoking has been linked to about 90 percent of all lung cancer cases.

In addition to lung cancer, smoking also causes lung diseases such as chronic bronchitis and emphysema, and it has been found to exacerbate asthma symptoms in adults and children. Smoking is also associated with cancers of the mouth, pharynx, larynx, esophagus, stomach, pancreas, cervix, kidney, ureter, and bladder. The overall rates of death from cancer are twice as high among smokers as among nonsmokers, with heavy smokers having rates that are four times greater than those of nonsmokers. Cigarette smoking is the most important preventable cause of cancer in the United States. 

In addition to its ability to cause cancer, a relationship between cigarette smoking and coronary heart disease was first reported in the 1940s. Since that time, it has been well documented that smoking substantially increases the risk of heart disease, including stroke, heart attack, vascular disease, and aneurysm. It is estimated that nearly one-fifth of deaths from heart disease are attributable to smoking.

While we often think of medical consequences that result from direct use of tobacco products, passive or secondary smoke also increases the risk for many diseases. Environmental tobacco smoke (ETS) is a major source of indoor air contaminants; secondhand smoke is estimated to cause approximately 3,000 lung cancer deaths per year among nonsmokers and contributes to as many as 40,000 deaths related to cardiovascular disease. Exposure to tobacco smoke in the home increases the severity of asthma for children and is a risk factor for new cases of childhood asthma. ETS exposure has been linked also with sudden infant death syndrome. Additionally, dropped cigarettes are the leading cause of residential fire fatalities, leading to more than 1,000 such deaths each year. At higher doses, such as the nicotine that can be found in some insecticide sprays, nicotine can be extremely toxic, causing vomiting, tremors, convulsions, and death. Nicotine poisoning has been reported from accidental ingestion of insecticides by adults and ingestion of tobacco products by children and pets. Death usually results in a few minutes from respiratory failure caused by paralysis.

Laboratory research indicates that cigarette smoking causes toxic cardiovascular effects. For this reason, nicotine replacement medicines such as nicotine gum and the patch have been extensively evaluated for cardiovascular toxicity, especially for patients with cardiac disease. These trials suggest that use of nicotine replacements for smoking cessation does not increase cardiovascular risk. These findings are consistent with the generally slower and lower doses of nicotine obtained from the medicines as compared to tobacco products, and to the absence of carbon monoxide and numerous other toxins in tobacco smoke.

Smoking and pregnancy

In pregnant women, carbon monoxide (a lethal gas) and the high doses of nicotine obtained when they inhale tobacco smoke interferes with oxygen supply to the fetus. Nicotine readily crosses the placenta, and nicotine concentrations in the fetus can be as much as 15 percent higher than maternal levels. It appears that nicotine is concentrated in fetal blood, amniotic fluid, and breast milk. Another ingredient of tobacco smoke, carbon monoxide, has been shown to inhibit the release of oxygen into fetal tissues. These factors, combined, likely account for the developmental delays commonly seen in the fetuses and infants of smoking mothers.

Women who smoke during pregnancy are at greater risk than nonsmokers for premature delivery, and there is a risk of lower birth weight for infants carried to term. In the United States it is estimated that 20 percent or more of pregnant women smoke throughout their pregnancies. The adverse effects of smoking may occur in every trimester of pregnancy; they range from spontaneous abortions in the first trimester to increased premature delivery rates and decreased birth weights in the final trimester. The decreased birth weights seen in infants of mothers who smoke reflects a dose-dependent relationship: the more the woman smokes during pregnancy, the greater the reduction of infant birth weight. Conversely, women who give up smoking early in pregnancy have infants of similar weight to those of nonsmokers.

source: NIDA Research Report - Nicotine Addiction: NIH Publication No. 98-4342

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