when the tobacco product is no longer used (U.S. DHHS, 1988). In addition, the rate of absorption and therefore the speed of delivery of nicotine to the brain also play a significant role in the addictive potential of nicotine (Henningfield and Keenan, 1993). These factors contribute to the reinforcing effects or persistent use of nicotine and also may be responsible for day-to-day regulation of nicotine levels in tobacco users.

Psychoactive and reinforcing effects from nicotine are the result of the release of a number of neurotransmitters and hormones (Benowitz, 1999; U.S. DHHS, 1988; Watkins et al., 2000). This cascade of events is associated with mood modulation, cognitive and motor performance enhancements, and weight reduction. These effects may contribute to the initiation and maintenance of tobacco use. Chronic administration of nicotine can lead to neuroadaptation. One of the effects of neuroadaptation is the development of tolerance. Adaptation occurs so that the brain can maintain a state of homeostasis despite an increased release of neurotransmitters. This process includes receptor inactivation and desensitization and an increase or upregulation in receptor number (Benowitz, 1999). The extent of these changes could vary depending on the receptor subtype and site (Watkins et al., 2000). Tolerance may lead to individuals’ using more of the tobacco product or switching to higher nicotine-containing products.

Neuroadaptation may subsequently lead to withdrawal symptoms when the tobacco user is no longer exposed to the product. Withdrawal symptoms include negative affect (e.g., irritability, frustration or anger, anxiety, dysphoric or depressed mood), restlessness, difficulty in concentrating, insomnia, decreased heart rate, and increased appetite or weight (APA, 1994). These symptoms occur among regular users of cigarettes and smokeless tobacco (Hughes and Hatsukami, 1992). They are less pronounced with nicotine gum use, but this distinction blurs with prolonged use of the gum (Hughes et al., 1986b; West and Russell, 1985). Approximately 49% of self-quitting smokers and 87% of tobacco cessation program attendees meet Diagnostic and Statistical Manual of Mental Disorders (DSM) IIIR (APA, 1987, 1994) criteria for nicotine withdrawal syndrome (Hughes and Hatsukami, 1992). These withdrawal symptoms peak during the first week of abstinence and return to baseline levels by four weeks (Hughes et al., 1990a). The intensity of these symptoms is further reduced over the course of time. The only exception to this pattern is increased weight. Weight may continue to increase over six months, and a reduction may not be seen at all or only after several months of abstinence (Hughes et al., 1990a).

A major determinant of whether nicotine is likely to be addictive is the amount and speed of nicotine delivery. The route of delivery also determines the pattern of nicotine delivery (as discussed earlier). For



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