"Long-term exposure to nicotine produces biologic adaptations leading to reduced sensitivity to some of the effects of nicotine (tolerance) and symptoms of distress soon after cessation of drug use (withdrawal). Tolerance of nicotine in adolescent smokers may be related to onset of drug dependence, even though tolerance in adult smokers does not appear to be related to different indices of nicotine addiction. Withdrawal symptoms, especially self-reported cravings and negative affect, are related to some indices of addiction. A narrower focus on the individual withdrawal symptoms most strongly related to relapse, such as negative affect (e.g., depressed mood), may increase understanding of the underlying mechanisms associated with the maintenance of nicotine addiction and requires further study.
"Positive reinforcement from nicotine may play a more significant role in the initiation of smoking, and negative reinforcement, particularly relief from withdrawal, is an important contributor to the persistence of smoking and relapse. Measures of nicotine’s reinforcing effects, especially the most common measure—self-reported number of cigarettes smoked per day—are consistently related to other indices of addiction, including the risk of relapse. However, other objective measures of nicotine’s reinforcing effects, especially those reflecting persistence in smoking behavior, may provide even stronger markers of addiction for predicting clinical outcomes and for testing the efficacy of new treatments or tobacco products. Such measures may also be useful as endophenotypes of dependence for future research into the etiology of addiction, including the influence of a person’s genetic composition. Therefore, the development of these validated markers and measures for nicotine and smoking reinforcement is critical for future research examining the etiology and treatments for nicotine addiction and for tobacco product testing."


US Department of Health and Human Services. "How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General." Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010, p. 124.