Individual variability in responses to nicotine

Individual variability in acute responses to nicotine, which may be defined as variable magnitude of effects following controlled dosing, is generally attributed to stable characteristics of tobacco users such as genetic/constitutional factors or to chronic behavioral factors (e.g., long-term use of other drugs). Often overlooked, however, is that such variability may also be due to the transient influence of the situational factors in which people consume nicotine, such as acute stress or physical activity. Results of selected studies from the author's laboratory provide examples of each of these sources of variability in nicotine responding on subjective, behavioral, and physiological measures. All studies used a nasal spray method of nicotine dosing or controlled smoking (paced puffing) to control acute nicotine exposure, an essential methodological feature of any research on individual differences in acute responses to nicotine. As an example of genetic/constitutional factors, gender differences in nicotine responding have begun to receive some attention, with few differences emerging. However, females may be more responsive than males to nonnicotine stimuli associated with smoking (e.g., sight and taste of smoke). In terms of chronic behavioral factors, long-term use of nicotine produces attenuation of most subjective and some behavioral effects of nicotine, reflecting chronic tolerance, and the possibility that chronic use of other drugs may alter responses to nicotine (i.e., cross-tolerance or cross-sensitization) deserves greater study. Of particular emphasis in this review is the modulating influence of acute situational factors on nicotine responding. Human studies have shown that magnitude of nicotine's subjective effects may depend on the predrug subjective state, level of physical activity vs. rest, and concurrent acute intake of other drugs, among other situational factors. Proper consideration of these situational factors may reveal the greatest source of individual variability in responding to nicotine and clarify the impact of more stable genetic/constitutional or chronic environmental factors.