Cigarette smoking remains a leading cause of preventable disease and premature death in the United States and other countries. On average, 435,000 people in the United States die prematurely from smoking-related diseases each year; overall, smoking causes 1 in 5 deaths. The chance that a lifelong smoker will die prematurely from a complication of smoking is approximately 50%.1
Tobacco use is a major cause of death from cancer, cardiovascular disease, and pulmonary disease. Cigarette smoking is also a risk factor for respiratory tract and other infections, osteoporosis, reproductive disorders, adverse postoperative events and delayed wound healing, duodenal and gastric ulcers, and diabetes. In addition, smoking has a strong association with fire-related and trauma-related injuries. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke. Although nicotine plays a minor role, if any, in causing smoking-induced diseases, addiction to nicotine is the proximate cause of these diseases.
Currently, about 45 million Americans smoke tobacco. Seventy percent of smokers say they would like to quit, and every year, 40% do quit for at least 1 day.2 Some highly addicted smokers make serious attempts to quit but are able to stop only for a few hours.3 Moreover, the 80% who attempt to quit on their own return to smoking within a month, and each year, only 3% of smokers quit successfully. Unfortunately, the rate at which persons — primarily children and adolescents — become daily smokers nearly matches the quit rate, so the prevalence of cigarette smoking has declined only very slowly in recent years.2
This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. Tobacco addiction (like all drug addictions) involves the interplay of pharmacology, learned or conditioned factors, genetics, and social and environmental factors (including tobacco product design and marketing)4 (Fig. 1). The pharmacologic reasons for nicotine use are enhancement of mood, either directly or through relief of withdrawal symptoms, and augmentation of mental or physical functions.