Cigarettes and Other Nicotine Products

   Nicotine is one of the most heavily used addictive drugs in the United States. Cigarette smoking has been the most popular method of taking nicotine since the beginning of the 20th century. In 1998, 60 million Americans were current cigarette smokers (28 percent of all Americans aged 12 and older), and 4.1 million were between the ages of 12 and 17 (18 percent of youth in this age bracket).

   In 1989, the U.S. Surgeon General issued a report that concluded that cigarettes and other forms of tobacco, such as cigars, pipe tobacco, and chewing tobacco, are addictive and that nicotine is the drug in tobacco that causes addiction. In addition, the report determined that smoking was a major cause of stroke and the third leading cause of death in the United States.

   Health Hazards

   Nicotine is highly addictive. It is both a stimulant and a sedative to the central nervous system. The ingestion of nicotine results in an almost immediate "kick" because it causes a discharge of epinephrine from the adrenal cortex. This stimulates the central nervous system, and other endocrine glands, which causes a sudden release of glucose. Stimulation is then followed by depression and fatigue, leading the abuser to seek more nicotine. Nicotine is absorbed readily from tobacco smoke in the lungs, and it does not matter whether the tobacco smoke is from cigarettes, cigars, or pipes.

   Nicotine also is absorbed readily when tobacco is chewed. With regular use of tobacco, levels of nicotine accumulate in the body during the day and persist overnight. Thus, daily smokers or chewers are exposed to the effects of nicotine for 24 hours each day. Nicotine taken in by cigarette or cigar smoking takes only seconds to reach the brain but has a direct effect on the body for up to 30 minutes.

   Research has shown that stress and anxiety affect nicotine tolerance and dependence. The stress hormone corticosterone reduces the effects of nicotine; therefore, more nicotine must be consumed to achieve the same effect. This increases tolerance to nicotine and leads to increased dependence. Studies in animals have also shown that stress can directly cause relapse to nicotine self-administration after a period of abstinence.

   Other studies have shown that animals cannot discriminate between the effects of nicotine and the effects of cocaine. Studies have also shown that nicotine self-administration sensitizes animals to self-administer cocaine more readily. Addiction to nicotine results in withdrawal symptoms when a person tries to stop smoking. For example, a study found that when chronic smokers were deprived of cigarettes for 24 hours, they had increased anger, hostility, and aggression, and loss of social cooperation. Persons suffering from withdrawal also take longer to regain emotional equilibrium following stress. During periods of abstinence and/or craving, smokers have shown impairment across a wide range of psychomotor and cognitive functions, such as language comprehension.

   Women who smoke generally have earlier menopause. If women smoke cigarettes and also take oral contraceptives, they are more prone to cardiovascular and cerebrovascular diseases than are other smokers; this is especially true for women older than 30.

   Pregnant women who smoke cigarettes run an increased risk of having stillborn or premature infants or infants with low birth weight. Children of women who smoked while pregnant have an increased risk for developing conduct disorders. National studies of mothers and daughters have also found that maternal smoking during pregnancy increased the probability that female children would smoke and would persist in smoking.

   Adolescent smokeless tobacco users are more likely than nonusers to become cigarette smokers. Behavioral research is beginning to explain how social influences, such as observing adults or other peers smoking, affect whether adolescents begin to smoke cigarettes. Research has shown that teens are generally resistant to many kinds of anti-smoking messages.

   In addition to nicotine, cigarette smoke is primarily composed of a dozen gases (mainly carbon monoxide) and tar. The tar in a cigarette, which varies from about 15 mg for a regular cigarette to 7 mg in a low-tar cigarette, exposes the user to a high expectancy rate of lung cancer, emphysema, and bronchial disorders. The carbon monoxide in the smoke increases the chance of cardiovascular diseases.

   The Environmental Protection Agency has concluded that secondhand smoke causes lung cancer in adults and greatly increases the risk of respiratory illnesses in children and sudden infant death. 

   Promising Research  

   Research has shown that nicotine, like cocaine, heroin, and marijuana, increases the level of the neurotransmitter dopamine, which affects the brain pathways that control reward and pleasure. Scientists now have pinpointed a particular molecule (the beta 2 subunit of the nicotine cholinergic receptor) as a critical component in nicotine addiction. Mice that lack this molecule fail to self-administer nicotine, implying that without the b2 molecule, the mice do not experience the positive reinforcing properties of nicotine. This new finding identifies a potential site for targeting the development of anti-nicotine addiction medications.

   Other new research found that individuals have greater resistance to nicotine addiction if they have a genetic variant that decreases the function of the enzyme CYP2A6. The decrease in CYP2A6 slows the breakdown of nicotine and protects individuals against nicotine addiction. Understanding the role of this enzyme in nicotine addiction gives a new target for developing more effective medications to help people stop smoking. Medications might be developed that can inhibit the function of CYP2A6, thus providing a new approach to preventing and treating nicotine addiction.

   Another study found dramatic changes in the brain's pleasure circuits during withdrawal from chronic nicotine use. These changes are comparable in magnitude and duration to similar changes observed during the withdrawal from other abused drugs such as cocaine, opiates, amphetamines, and alcohol. Scientists found significant decreases in the sensitivity of the brains of laboratory rats to pleasurable stimulation after nicotine administration was abruptly stopped. These changes lasted several days and may correspond to the anxiety and depression experienced by humans for several days after quitting smoking "cold turkey." The results of this research may help in the development of better treatments for the withdrawal symptoms that may interfere with individual's attempts to quit smoking.

 

   Treatment

   Research suggests that smoking cessation should be a gradual process because withdrawal symptoms are less severe in those who quit gradually than in those who quit all at once. Rates of relapse are highest in the first few weeks and months and diminish considerably after 3 months.

   Studies have shown that pharmacological treatment combined with psychological treatment, including psychological support and skills training to overcome high-risk situations, results in some of the highest long-term abstinence rates.

   Behavioral economic studies find that alternative rewards and reinforcers can reduce cigarette use. One study found that the greatest reductions in cigarette use were achieved when smoking cost was increased in combination with the presence of alternative recreational activities.

   Nicotine chewing gum is one medication approved by the Food and Drug Administration (FDA) for the treatment of nicotine dependence. Nicotine in this form acts as a nicotine replacement to help smokers quit the smoking habit.

   The success rates for smoking cessation treatment with nicotine chewing gum vary considerably across studies, but evidence suggests that it is a safe means of facilitating smoking cessation if chewed according to instructions and restricted to patients who are under medical supervision.

   Another approach to smoking cessation is the nicotine transdermal patch, a skin patch that delivers a relatively constant amount of nicotine to the person wearing it. A research team at NIDA's Division of Intramural Research studied the safety, mechanism of action, and abuse liability of the patch that was consequently approved by FDA. Both nicotine gum and the nicotine patch, as well as other nicotine replacements such as sprays and inhalers, are used to help people fully quit smoking by reducing withdrawal symptoms and preventing relapse while undergoing behavioral treatment.

   Another tool in treating nicotine addiction is a medication that goes by the trademark Zyban. This is not a nicotine replacement, as are the gum and patch. Rather, this works on other areas of the brain, and its effectiveness is in helping to make controllable nicotine craving or thoughts about cigarette use in people trying to quit.

   In the future, a nicotine vaccine may be an effective method for preventing and treating tobacco addiction. The vaccine would prevent nicotine from reaching the brain so as to reduce its effects and help keep people from becoming addicted.

   Scientists recently developed an experimental nicotine vaccine consisting of a nicotine derivative attached to a large protein. The scientists injected a single dose of nicotine into vaccinated rats and found that the amount of nicotine reaching the brain was reduced by 64%. Further, the researchers found that administering doses of nicotine antibodies similar to those that are ordinarily produced by the vaccine greatly reduced the rise in blood pressure produced by a nicotine injection. The antibodies also completely prevented the increased movements ordinarily seen when rats are injected with nicotine.

   The next steps will be to conduct additional safety studies, followed by clinical trials with the

   vaccine in human volunteers. These clinical trials are currently scheduled to begin in early 2002.