, Volume 109, Issue 4, pp 449–456

Nicotine elimination and tolerance in non-dependent cigarette smokers

  • Saul Shiffman
  • Monica Zettler-Segal
  • Jon Kassel
  • Jean Paty
  • Neal L. Benowitz
  • Gregory O'Brien
Original Investigations


Although most smokers are nicotine-dependent, recent studies suggest that some very light smokers (“chippers”, who smoke fewer than five cigarettes per day) may smoke for decades without developing dependence. It was considered that slowed nicotine elimination and/or reduced nicotine tolerance might underlie chippers' ability to maintain smoking at such low levels. To evaluate this hypothesis, we studied the elimination kinetics and pharmacodynamics of nicotine in chippers and matched regular smokers. Plasma nicotine levels and cardiovascular responses were observed for several hours after subjects were administered uniform doses of tobacco smoke. Chippers did show less chronic nicotine tolerance, but only on some response measures. Their rates of nicotine elimination equaled those of regular smokers. This finding, when coupled with other data about chippers' smoking patterns and nicotine absorption, establish that chippers cannot maintain substantial plasma nicotine levels between cigarettes, and thus suggest that attempts to maintain minimal trough levels of nicotine do not underlie chippers' smoking.

Key words

Nicotine Dependence Elimination rate Tolerance Pharmacokinetics Pharmacodynamics 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander BK, Hadaway PF (1982) Opiate addiction: the case for an adaptive orientation. Psychol Bull 92:367–381Google Scholar
  2. Benowitz NL (1983) The use of biological fluid samples in assessing tobacco smoke consumption. In: Grabowski J, Bell KS (eds) Measurement in the analysis and treatment of smoking behavior. Public Health Service, Bethesda, MD, pp 6–26Google Scholar
  3. Benowitz NL, Kuyt F, Jacob P (1982a) Circadian study of blood nicotine concentrations during cigarette smoking. Clin Pharmacol Ther 32:758–764Google Scholar
  4. Benowitz NL, Jacob P, Jones RT, Rosenberg J (1982b) Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther 221:368–372Google Scholar
  5. Benowitz NL, Jacob P, Kozlowski LT, Yu L (1986) Influence of smoking fewer cigarettes on exposure to tar, nicotine, and carbon monoxide. New Engl J Med 315:1310–1313Google Scholar
  6. Cohen S, Lichtenstein E, Prochaska JO, Rossi JS, Gritz ER, Carr CR, Orleans CT, Schoenbach VJ, Biener VJ, Abrams D, DiClemente C, Curry C, Marlatt GA, Cummings KM, Emont SL, Giovino G, Ossip-Klein D (1989) Debunking myths about self-quitting: Evidence from 10 prospective studies of persons who attempt to quit smoking by themselves. Am Psychol 44:1355–1365Google Scholar
  7. Fagerstrom K-O (1978) Measuring degree of physical dependence to tobacco with reference to individualization of treatment. Addic Behav 3:235–241Google Scholar
  8. Gilbert DG (1979) Paradoxical tranquilizing and emotion-reducing effects of nicotine. Psychol Bull 86:643–661Google Scholar
  9. Harding WM, Zinberg NE, Stelmack SM, Barry M (1980) Formerly-addicted-now-controlled opiate users. Int J Addict 15:47–60Google Scholar
  10. Herman CP (1974) External and internal cues as determinants of the smoking behavior of light and heavy smokers. J Person Soc Psychol 30:664–672Google Scholar
  11. Holford NHG, Sheiner LB (1981) Understanding the dose-effect relationship: Clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet 6:429–453Google Scholar
  12. Hughes JR, Gust SW, Pechacek TF (1987) Prevalence of tobacco dependence and withdrawal. Am J Psychiatry 144:205–208Google Scholar
  13. Jacob P, Wilson M, Benowitz NL (1981) Improved gas chromatographic method for the determination of nicotine and cotinine in biologic fluids. J Chromatogr 222:61–70Google Scholar
  14. Jaffe JH (1980) Drug addiction and drug abuse. In: Goodman AG, Gilman A (eds) The pharmacological basis of therapeutics. McGraw Hill, New YorkGoogle Scholar
  15. Kandel DB, Logan JA (1984) Patterns of drug use from adolescence to young adulthood: 1. Periods of risk for initiation, continued use, and discontinuation. Am J Public Health 74:660–666Google Scholar
  16. Lando HA (1981) Effects of preparation, experimenter contact, and a maintained reduction alternative on a broad-spectrum program for eliminating smoking. Addict Behav 6:123–133Google Scholar
  17. Levinson BL, Shapiro D, Schwartz GE, Tursky B (1971) Smoking elimination by gradual reduction. Behav Ther 2:477–487Google Scholar
  18. McKennell AC (1970) Smoking motivation factors. Br J Soc Clin Psychol 9:8–22Google Scholar
  19. McKennell AC, Thomas RK (1967) Adults' and adolescents' smoking habits and attitudes. British Ministry of Health, LondonGoogle Scholar
  20. McNeill AD, West R, Jarvis M, Jackson P, Bryant A (1986) Cigarette withdrawal symptoms in adolescent smokers. Psychopharmacology 90:533–536Google Scholar
  21. Miller PM, Fredericksen LW, Hosford RL (1979) Social interaction and smoking topography in heavy and light smokers. Addic Behav 4:147–153Google Scholar
  22. National Center for Health Statistics (1979–1981) Health interview survey. Department of Health and Human Services, Washington DCGoogle Scholar
  23. Perkins KA, Epstein LH, Stiller RL, Marks BL, Jacob RG (1989) Chronic and acute tolerance to the heart rate effects of nicotine. Psychopharmacology 97:529–534Google Scholar
  24. Perkins KA, Epstein LH, Stiller RL, Sexton JE, Jacob RG, Solberg R, Debski TT (1990) Chronic tolerance to the heart rate effects of nicotine: a replication and extension. Paper presented at the Society of Behavioral Medicine, Chicago, IIIGoogle Scholar
  25. Pomerleau OF, Pomerleau CS (1984) Neuroregulators and the reinforcement of smoking: towards a biobehavioral explanation. Neurosci Biobehav Rev 8:503–513Google Scholar
  26. Pomerleau OF, Fertig JB, Seyler LE, Jaffe J (1983) Neuroendicrine reactivity to nicotine in smokers. Psychopharmacology 81:61–67Google Scholar
  27. Pomerleau OF, Pomerleau CS, Rose JE (1989) Controlled dosing of nicotine: a review of problems and progress. Ann Behav Med 11:158–163Google Scholar
  28. Pomerleau OF, Collins AC, Shiffman S, Pomerleau CS (1992) Why some people smoke: the role of constitutional factors. Unpublished manuscript, University of MichiganGoogle Scholar
  29. Porchet HC, Benowitz NL, Sheiner LB (1988) Pharmacodynamic model of tolerance: Application to nicotine. J Pharmacol Exp Ther 244:231–236Google Scholar
  30. Powell DH (1973) A pilot study of occasional heroin users. Arch Gen Psychiatry 28:586–594Google Scholar
  31. Rogers RG, Crank J (1988) Ethnic differences in smoking patterns: Findings from the NHIS. Public Health Rep 103:387–393Google Scholar
  32. Rose JE, Tashkin DP, Ertle A, Zinser MC, Lafer R (1985) Sensory blockade of smoking satisfaction. Pharmacol Biochem Behav 23:289–293Google Scholar
  33. Russel MAH, Feyerabend C (1978) Cigarette smoking: a dependence on high-nicotine boli. Drug Metab Rev 8:29–57Google Scholar
  34. Russell MAH, Jarvis MJ, Jones G, Feyerabend C (1990) Nonsmokers show acute tolerance to subcutaneous nicotine. Psychopharmacology 102:56–58Google Scholar
  35. Shapiro D, Tursky B, Schwartz GE, Shnidman SR (1971) Smoking on cue: a behavioral approach to smoking reduction. J Health Soc Behav 12:108–113Google Scholar
  36. Shiffman S (1989) Tobacco “chippers” — individual differences in tobacco dependence. Psychopharmacology 97:539–547Google Scholar
  37. Shiffman S (1991) Refining models of dependence: variations across persons and situations. Br J Addic 86:611–615Google Scholar
  38. Shiffman S, Fischer LA, Zettler-Segal M, Benowitz NE (1990) Nicotine exposure in non-dependent smokers. Arch Gen Psychiatry 47:333–336Google Scholar
  39. Shiffman S, Paty J, Kassel J, Zettler-Segal M (1991) Self-monitored situational correlates of light and heavy smokers. Unpublished manuscript, University of PittsburghGoogle Scholar
  40. Shiffman S, Paty J, Kassel J, Gnys M (1992) Effects of nicotine deprivation on dependent and nondependent smokers. Unpublished manuscript, University of PittsburghGoogle Scholar
  41. Siegel S (1983) Classical conditioning, drug tolerance, and drug dependence. In: Smart R, Glaser F, Israel Y, Kalant H, Popham R, Schmidt W (eds) Research advances in alcohol and drug problems, vol 7. Plenum Press, New York, NY, pp 207–246Google Scholar
  42. US Public Health Service (eds) (1988) The health consequences of smoking: nicotine addiction, a report of the surgeon general. US Department of Health and Human Services, Rockville, MDGoogle Scholar
  43. Wesnes K, Warburton DM (1983) Smoking, nicotine, and human performance. Pharmacol Ther 21:189–208Google Scholar
  44. Wesnes K, Warburton DM, Matz B (1983) Effects of nicotine on stimulus sensitivity and response bias in a visual vigilance task. Neuropsychobiology 9:41–44Google Scholar
  45. Wikler A (1980) Theories of tolerance to and physical dependence on opioids. In: Wikler A (ed) Opioid dependence. Plenum Press, New YorkGoogle Scholar
  46. Zinberg NE, Jacobson RC (1976) The natural history of “chipping”. Am J Psychiatry 33:37–40Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Saul Shiffman
    • 1
  • Monica Zettler-Segal
    • 1
  • Jon Kassel
    • 1
  • Jean Paty
    • 1
  • Neal L. Benowitz
    • 2
  • Gregory O'Brien
    • 1
  1. 1.Department of PsychologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations