Over the past decade, NIDA's nicotine-related research has provided crucial insights into the neurobiological and behavioral aspects of nicotine addiction, and this research has led the way to important advances in treating nicotine addiction.

Nicotine addiction takes a terrible toll on American health. More than 430,000 people die in this country each year from smoking-related causes, and the annual cost of these preventable illnesses-in health care expenditures and lost productivity-is more than $97 billion. Despite growing public awareness of the deadly dangers of tobacco, nearly 3,000 people younger than 18 become smokers every day and, once addicted, find it very difficult to stop.

Over the past decade, NIDA's nicotine-related research has provided crucial insights into the neurobiological and behavioral aspects of nicotine addiction, and this research has led the way to important advances in treating nicotine addiction. For example, NIDA-supported basic science research and clinical pharmacological studies played a major role in the development of nicotine replacement therapy-a skin patch or chewing gum that reduces the physical discomfort of nicotine withdrawal. Our behavioral science research has contributed to the development, testing, and validation of new behavioral therapies to help smokers resist the craving that often defeats the most determined efforts to stop smoking.

Many of the accomplishments of NIDA's nicotine research effort have been incorporated into a new set of recommendations for primary care practitioners, "Treating Tobacco Use and Dependence: A Clinical Practice Guideline." The recommendations, which were released by U.S. Surgeon General Dr. David Satcher in June, are based on an evaluation of nearly 6,000 peer-reviewed research studies. They endorse pharmacotherapies-sustained release bupropion or nicotine replacement therapy by patch, gum, inhaler, or nasal spray-as well as behavioral therapy, counseling, and support programs to help patients overcome their addiction to nicotine. NIDA-along with the National Cancer Institute; the National Heart, Lung, and Blood Institute; the Centers for Disease Control and Prevention; the Agency for Healthcare Research and Quality; The Robert Wood Johnson Foundation; and the University of Wisconsin Medical School's Center for Tobacco Research and Intervention-sponsored development of the guidelines.

The dividends from NIDA's ongoing investment in nicotine research are increasing. For example, investigators at the Minneapolis Medical Research Foundation have developed a vaccine that, in rats, produces nicotine-specific antibodies that reduce by as much as 65 percent the amount of nicotine that passes from the blood to the brain. The vaccine also prevents some of nicotine's cardiovascular effects and reduces the development of nicotine dependence. This research is a promising first step toward development of a medication that could limit the movement of nicotine from the blood to the brain, reducing the "rush" that addicted smokers experience when they light up and making it easier for them to quit (for more detailed information on this research, see "Nicotine Vaccine Moves Toward Clinical Trials"). Other NIDA-supported researchers have demonstrated important connections between addictions to nicotine and other addictive drugs. This knowledge can help us develop better therapies for patients with multiple addictions (see "Nicotine Craving and Heavy Smoking May Contribute to Increased Use of Cocaine and Heroin"). NIDA's program of research into genetic factors that influence nicotine addiction has identified a genetically determined variation in liver metabolism that significantly decreases the rate at which the body breaks down and eliminates nicotine from the blood. Individuals with this genetic trait are less likely to become addicted to nicotine and more likely to be able to quit if they do become addicted. NIDA-supported researchers have found a medication-methoxsalen-that inhibits nicotine metabolism in the same way as the genetic variation. Their studies of the effects of methoxsalen in humans suggest the possibility of developing an entirely new approach to pharmacological treatment of nicotine addiction (see "NIDA Researchers Identify Compound That Inhibits Nicotine Metabolism, Decreases Urge to Smoke").

An important part of NIDA's mission is dissemination of the knowledge gained through research. NIDA's newest "art card" describes the similarity between nicotine's addictive properties and those of other addictive drugs. The colorful postcards are distributed at restaurants, bookstores, and coffee shops.

Earlier this year, NIDA announced a new research program designed to expand our understanding of the basic science that influences neurobiological and behavioral effects of nicotine and other tobacco chemicals. This program will support investigations that further explain the connections between nicotine and regional brain metabolism, the roles of nicotinic receptors and endocrine regulation, genetic contributions to variations in susceptibility to nicotine addiction, and the neurobiological and behavioral components of nicotine craving.

NIDA's scientific inquiries have provided critical insights into numerous discrete features of nicotine addiction. But tobacco use and nicotine addiction are complex subjects that can only be truly understood as a dynamic interaction of genetic, environmental, neurophysiological, and behavioral effects. To give us the broad perspective we need to fully understand this interaction, last year NIDA joined with the National Cancer Institute and The Robert Wood Johnson Foundation to create seven Transdisciplinary Tobacco Use Research Centers (TTURCs) devoted to investigating new ways to combat tobacco use and nicotine addiction. The TTURCs represent an important new approach to research. They bring together collaborators who will have the freedom to investigate broad aspects of nicotine addiction, from factors that influence smoking initiation to the function of specific neurochemicals, and to study the issues at levels ranging from molecular genetics to peer interactions.

The deadly effects of nicotine reach from the individual cell to our national health. NIDA is committed to continuing and expanding a program of scientific research that provides comprehensive and detailed knowledge that can be transformed into effective tools to prevent and treat the chronic and catastrophic effects of nicotine addiction.