Basic biobehavioral research in tobacco control focuses on the interactions of biological, psychological, sociocultural, and other environmental processes in initiation of tobacco use, nicotine dependence, cessation, and relapse. INTRODUCTION We still do not know why some people adopt or cease behaviors that increase cancer risk, such as tobacco use. Such gaps in fundamental knowledge highlight the need for basic biobehavioral (pre-intervention) research to elucidate the links between biological, behavioral, and environmental influences and cancer risk behaviors. This knowledge is essential to develop more effective tobacco prevention and cessation interventions, to understand the mechanisms by which such interventions succeed or fail, and to target interventions to people most likely to benefit from them. We have made significant advances in our understanding of the psychosocial determinants of tobacco use. Many sociocultural, environmental, behavioral, and psychological factors are linked to cigarette smoking. These include: low income; use of tobacco by peers, parents, and other family members; poor academic performance and frequent school absences; and low-self esteem and depression. Further research is needed to explore the interdependencies of these factors. Significant gaps also exist in our understanding of the relationship between biology and behavior. The recent identification of genes that modify nicotine metabolism and regulate the activity of chemicals in the brain that affect mood changes and feelings of pleasure triggered by nicotine provides unique opportunities for studying these links. Genes in the brain's reward pathways have been implicated in a variety of addictive behaviors, including tobacco and alcohol use. Increased understanding of the underlying neurobiology of nicotine addiction, and of other biobehavioral factors in tobacco use, should lead to more effective, targeted approaches for tobacco prevention and smoking cessation. RECOMMENDATIONS Basic biobehavioral research should be conducted to understand the sociocultural, psychological, physiological, and genetic factors that influence the initiation of tobacco use, progression to nicotine addiction, and smoking cessation among children, adolescents, and adults. Despite our increased knowledge about why people begin to use tobacco products and how they become addicted to nicotine, many important questions about tobacco use and cessation remain. For example, why are some children and adolescents susceptible to tobacco use, while others seem impervious to social influences, such as peer pressure, media glamorization of smoking, and tobacco industry marketing? Why do some children and adolescents smoke for only a short period of time, while others develop long-term nicotine dependence? Research is needed to examine the complex interplay between social influences, psychological factors, and genetic vulnerabilities. Laboratory studies could probe the genetic and biological bases of nicotine metabolism and/or the rewarding effects of nicotine at different stages of development (e.g., childhood, adolescence, and adulthood) in relation to tobacco use. How these factors relate to gender and ethnicity also should be studied. Research to determine the critical thresholds for progression from occasional use of tobacco products to nicotine addiction also would aid in identifying appropriate levels of intervention at different stages of tobacco use. Special attention should be given to the primary and interactive effects of developmental factors, psychological comorbid disorders (such as depression and attention deficit hyperactivity disorder [ADHD]), and tobacco product design and marketing influences on youth initiation of tobacco use and nicotine dependence. While recent NCI initiatives have stimulated studies to determine why youths begin and continue to use tobacco, we need more research on young adults ages 18 to 25, a group that has increased its use of a variety of tobacco products. Collaborative research with NIDA would be appropriate. Additional pre-intervention research could consider the role of biological factors and their interaction with coexisting psychological disorders and sociocultural factors in smoking initiation, nicotine addiction, and tobacco use. Such research can enable us to learn more about how genetic factors that affect mood, behavior, and the metabolism of nicotine interact with coexisting sociocultural factors and psychological disorders to increase or reduce an individual's vulnerability to nicotine addiction. In addition, research is needed to explore and understand the brain as well as the bodily processes through which tobacco product design and genetic factors interact to influence initiation and cessation of tobacco use. For example, brain-imaging techniques could be used to study how genetic factors control the brain's response to nicotine use and withdrawal. Furthermore, research is needed into the basic neurobiological processes and mechanisms related to nicotine addiction. Research in animals and cellular models is needed in this area. The findings from such research could contribute to the development of new medications to aid smoking cessation. Research should be conducted to understand the influence of different tobacco products and alternative nicotine delivery devices/systems on initiation and cessation of tobacco use as well as nicotine addiction. Different tobacco products and alternative nicotine delivery devices/systems contain different amounts of nicotine and deliver it in different ways to the body. These differences in the way nicotine is administered affect both its addictive and treatment potential and directly influence initiation of tobacco use, nicotine addiction, and cessation from tobacco use. Therefore, it is important to conduct biobehavioral research on individuals' responses to new nicotine delivery devices and tobacco products. Consideration should be given to whether the NCI should support harm reduction strategies. If so, the findings from biobehavioral research would provide an important and critical foundation. THE IMPACT OF BIOBEHAVIORAL RESEARCH Major research breakthroughs have made it possible to examine the biological bases of tobacco use and nicotine addiction, including the role of genetic factors and ethnicity in nicotine metabolism. In the short term, research in this area will help identify pre-existing biological vulnerabilities and determine how their interactions with sociocultural and psychological influences affect tobacco initiation, addiction, and cessation. In the long term, the findings from basic biobehavioral research will provide the scientific knowledge needed to develop more effective tobacco use prevention and cessation interventions, both behavioral and pharmacological, that are tailored to the unique needs of individuals. Increased understanding of the biobehavioral underpinnings of tobacco use and dependence also will be key to informing both public policy and public health practitioners about how to better target tobacco prevention and treatment policies and strategies for youth and adults.