Cigarette smoking remains the single leading preventable cause of death in the United States. Every year in the United States, there are nearly 500,000 smoking-attributable deaths, the majority due to neoplasms and cardiovascular disease. Despite these grim statistics, however, smoking prevalence, which peaked at 40% in the 1960’s and decreased steadily through the 1980’s, has declined much more slowly since 1990—even though over 70% of current smokers state that they would like to quit. The United States Public Health Service once aimed to bring the adult smoking rate in the United States to 15% by the year 2000; we are still quite a ways from achieving that goal.

This situation is probably a by-product of the great success of public health campaigns over the past three decades. As the "easy quits" and casual smokers are eliminated from the smoker pool or discouraged from initiation via these measures, there is mounting evidence that smoking is not randomly distributed but rather is becoming increasingly concentrated in people who for various reasons may be more susceptible to the blandishments of nicotine and/or have greater difficulty quitting. These at-risk populations include 1) people who are highly nicotine dependent; 2) people of low socioeconomic status; 3) people with other drug dependencies, most notably alcohol; and 4) people with cognitive or affective deficits amenable to management by nicotine.

The methods that have brought the smoking rate from 40% to a little over 20% are unlikely to achieve such dramatic successes with today’s refractory smokers. Unless a better understanding of phenotypic and genotypic differences that lead some people to smoke and others to reject smoking is attained, cigarette smoking will continue to be a national and worldwide tragedy. The University of Michigan Nicotine Research Laboratory is dedicated to carrying out a broad research agenda, using a wide variety of strategies, that should lead to a better understanding of the mechanisms underlying nicotine self-administration in humans, and ultimately to the development of a new generation of interventions that will meet the needs of treatment-resistant smokers.