Progress in Neuro-Psychopharmacology and Biological Psychiatry
Changes in craving for a cigarette and arterial nicotine plasma concentrations in abstinent smokers
Introduction
It is widely accepted that nicotine is a major contributor to tobacco dependence (USDHHS, Report of the Surgeon General, 1988). Nicotine blood concentrations are correlated with many of the physiologic effects associated with smoking, such as increases in heart rate and blood pressure, and decreases in skin temperature Benowitz et al., 1982, Fattinger et al., 1997, Porchet et al., 1988. However, the relationship between nicotine concentrations and changes in subjective effects in chronic smokers such as craving, relaxation, sickness, and nervousness is less well delineated. Being able to demonstrate a relationship between these subjective parameters and nicotine blood concentrations would be of more practical interest than showing a relationship between nicotine concentrations and physiologic effects. Subjective effects such as relaxation, increased alertness, or a decrease in early withdrawal symptoms such as craving appear to contribute more to the development of nicotine dependence (Bergen and Caporaso, 1999). Determining the amount and rate of nicotine administration associated with the reinforcing effects of nicotine would be helpful in the design of future nicotine replacement products used for smoking cessation.
In this study, the authors hypothesized that arterial nicotine plasma concentrations following smoking the first cigarette of the day would be significantly correlated with changes in subjective parameters associated with smoking cigarettes in smokers. The authors also hypothesized that smoking a denicotinized cigarette would cause fewer changes in the subjective parameters associated with smoking than an average nicotine cigarette. It is further hypothesized that changes in subjective effects would be primarily produced by the first tobacco cigarette of the day. Smoking another cigarette within the next hour might add little to the subjective effects produced by the first cigarette, regardless of nicotine blood levels produced by the second cigarette.
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Subjects
This study was approved by the Investigational Review Board for Human Subject Research at The University of Michigan Medical Center. Subjects were monetarily reimbursed for their time and inconvenience as participants in this study. Individuals who smoked cigarettes were recruited via advertisements in local newspapers and community bulletin boards. Following a preliminary screening over the telephone, those who appeared eligible were invited to an interview, during which the study was
Study population
Twenty-one smokers participated in the smoking study. Some data points were missing for three subjects but all available data for these subjects were included in the results.
The demographic characteristics of the subjects are listed in Table 1. Because there were no significant differences in sex, age, ethnicity, FTND scores, number of cigarettes smoked per day, baseline CO values, years of smoking, or FTC nicotine content of usual cigarette between the groups they were combined in the data
Rationale for the use of arterial nicotine concentrations
Due to the initial uptake of nicotine by body tissues, arterial blood is more likely to provide a useful index of the concentrations of nicotine seen by the brain shortly after smoking a cigarette. Even though collection of arterial blood is more technically difficult and invasive than venous blood collection, arterial blood was obtained in this study because this measure should provide the best chance of determining if there might be a meaningful relationship between nicotine pharmacokinetic
Conclusion
In our sample, the reduction in craving was significantly correlated with the AUC of nicotine following AN1, indicating that at least one subjective measure of nicotine effect is related to nicotine pharmacokinetics. While a positive correlation does not prove causation, it does imply that there is strong relationship between a reduction of craving for a cigarette and the amount of nicotine delivered in the first cigarette of the day. A single cigarette delivers a sufficient quantity of
Acknowledgements
This research was conducted using funds provided by: U.S. Public Heath Service; grant number: DA-10992, grant sponsor: National Institute on Drug Abuse, National Institutes of Health. The authors would also like to acknowledge the skill and hard work contributed to this project by Teresa Woike, RN.
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