, Volume 173, Issue 1–2, pp 18–26 | Cite as

Do smokers self-administer pure nicotine? A review of the evidence




Nicotine is almost universally believed to be the primary agent motivating tobacco smoking and the main impediment to cessation. A principal argument in support of the presumed reinforcing properties of nicotine is that smokers self-administer pure nicotine. However, the evidence for nicotine self-administration in smokers has not been critically examined.


To review and examine the empirical basis for the assertion that smokers self-administer pure nicotine.


We reviewed all the studies we were able to locate that are cited as demonstrating self-administration of nicotine, isolated from tobacco, in normal smokers and non-smokers. These studies investigated self-administration of intravenous nicotine, nicotine gum and nicotine spray. Using the authors’ own criteria, we examined whether these studies in fact demonstrate nicotine-self administration.


None of the studies we reviewed demonstrated nicotine self-administration in smokers. Both smokers and non-smokers failed to show preference for nicotine over placebo in any of these studies, including in a series of six reports of overnight abstinent smokers having access to nicotine nasal spray, a rapidly absorbed form of nicotine.


The common statement that smokers self-administer pure nicotine lacks empirical support. Smokers in fact do not administer pure nicotine in any of the forms studied to date, even when abstinent and presumably nicotine-deprived. This conclusion necessitates a critical re-examination of the nicotine addiction thesis.


Nicotine Self-administration Dependence Addiction Smoking 


  1. Atrens DM (2001) Nicotine as an addictive substance: a critical examination of the basic concepts and empirical evidence. J Drug Issues 31:325–394Google Scholar
  2. Balfour DJ, Fagerstrom KO (1996) Pharmacology of nicotine and its therapeutic use smoking cessation and neurodegenerative disorders. Pharmacol Ther 72:51–81CrossRefPubMedGoogle Scholar
  3. Benowitz NL (1996) Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol 36:597–613PubMedGoogle Scholar
  4. Benowitz NL (1999) Nicotine addiction. Prim Care 26:611–631PubMedGoogle Scholar
  5. Buchhalter AR, Schrinel L, Eissenberg T (2001) Withdrawal-suppressing effects of a novel smoking system: comparison with own brand, not own brand, and de-nicotinized cigarettes. Nicotine Tobacco Res 3:111–118CrossRefGoogle Scholar
  6. Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2001) Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Behav 70:515–530PubMedGoogle Scholar
  7. Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2002) Environmental stimuli promote the acquisition of nicotine self-administration in rats. Psychopharmacology 163:230–237CrossRefPubMedGoogle Scholar
  8. Dar R, Frenk H (2002) Nicotine self-administration in animals: a reevaluation. Addict Res Theory 10:545–579Google Scholar
  9. De Wit H, McCracken SG (1990) Ethanol self-administration in males with and without an alcoholic first-degree relative. Alcohol Clin Exp Res 14:63–70PubMedGoogle Scholar
  10. Donny EC, Caggiula AR, Mielke MM, Jacobs KS, Rose C, Sved AF (1998) Acquisition of nicotine self-administration in rats: the effect of dose, feeding schedule, and drug contingency. Psychopharmacology 136:83–90PubMedGoogle Scholar
  11. Foltin RW, Fischman MW (1992) Self-administration of cocaine by humans: choice between smoke and intravenous cocaine. J Pharmacol Exp Ther 261:841–849PubMedGoogle Scholar
  12. Frenk H, Dar R (2000) A critique of nicotine addiction. Kluwer Academic Publishers, BostonGoogle Scholar
  13. Goldberg SR, Henningfield JE (1983) Intravenous nicotine self-administration in humans and squirrel monkeys. Neurosci Lett 14:S140Google Scholar
  14. Goldberg SR, Henningfield JE (1986) Nicotine as a reinforcer in humans and experimental animals. Paper presented at symposium on Progress in Understanding the Relationship between the Pharmacological Effects of Nicotine and Human Tobacco Dependence, held at annual meeting of American Society for Pharmacology and Experimental Therapeutics. Baltimore, Md. (cf. US Department of Health and Human Services, 1988)Google Scholar
  15. Gori GB (1996) Failings of the disease model of addiction. Human Psychopharmacol 11:S33–S38CrossRefGoogle Scholar
  16. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A (1999) Randomized comparative trail of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Int Med 159:2033–2038Google Scholar
  17. Henningfield JE, Goldberg SR (1983) Control of behavior by intravenous nicotine injections in human subjects. Pharmacol Biochem Behav 19:1021–1026Google Scholar
  18. Henningfield JE, Keenan RM (1993) Nicotine delivery kinetics and abuse liability. J Consult Clin Psychol 61:743–750CrossRefPubMedGoogle Scholar
  19. Henningfield JE, Miyasato K, Jasinski DR (1983) Cigarette smokers self-administer intravenous nicotine. Pharmacol Biochem Behav 19:887–890PubMedGoogle Scholar
  20. Hughes JR, Pickens RW, Spring W, Keenan RM (1985) Instructions control whether nicotine will serve as a reinforcer. J Pharmacol Exp Ther 235:106–112PubMedGoogle Scholar
  21. Hughes JR, Strickler G, King D, Higgins ST, Fenwick JF, Gulliver SB, Mireault G (1989) Smoking history, instructions and the effects of nicotine: two pilot studies. Pharmacol Biochem Behav 34:149–155PubMedGoogle Scholar
  22. Hughes JR, Rose GL, Callas PW (2000a) Do former smokers respond to nicotine differently from never smokers? A pilot study. Nicotine Tobacco Res 2:255–262CrossRefGoogle Scholar
  23. Hughes JR, Rose GL, Callas PW (2000b) Nicotine is more reinforcing in smokers with a past history of alcoholism than in smokers without this history. Alcohol Clin Exp Res 24:1633–1638PubMedGoogle Scholar
  24. Jacober A, Hasenfratz M, Battig K (1994) Cigarette smoking: habit or nicotine maintenance? Effects of short-term smoking abstinence and oversmoking. Hum Psychopharmacol 9:117–123Google Scholar
  25. Juliano LM, Brandon TH (2002) Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor. J Abnormal Psychol 111:88–97CrossRefGoogle Scholar
  26. Kenford SL, Wetter DW, Smith SS, Jorenby DE, Fiore MC, Baker TB (2002) Predicting relapse back to smoking: Contrasting affective and physical models of dependence. J Consult Clin Psychol 70:216–277CrossRefPubMedGoogle Scholar
  27. Kozlowski LT, Porter CQ, Orleans CT, Pope MA, Heatherton T (1994) Predicting smoking cessation with self-reported measures of nicotine dependence: FTQ, FTND, and HSI. Drug Alcohol Depend 34:211–216PubMedGoogle Scholar
  28. Kozlowski LT, Henningfield JE, Brigham J (2001) Cigarettes, nicotine and health. Sage Publications, LondonGoogle Scholar
  29. McDonald RV, Parker LA, Siegel S (1997) Conditioned sucrose aversion produced by naloxone precipitated withdrawal form acutely administered morphine. Pharmacol Biochem Behav 58:1003–1008PubMedGoogle Scholar
  30. Perkins KA, DiMarco A, Grobe JE, Scierka A, Stiller RL (1994a) Nicotine discrimination in male and female smokers. Psychopharmacology 116:407–413Google Scholar
  31. Perkins KA, Sexton JE, Reynolds WA, Grobe JE, Fonte C, Stiller RL (1994b) Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray. Pharmacol Biochem Behav 47:295–299PubMedGoogle Scholar
  32. Perkins KA, Grobe JE, Damico D, Fonte C, Wilson AS, Stiller RL (1996a) Low-dose nicotine nasal spray use and effects during initial smoking cessation. Exp Clin Psychopharmacol 4:157–165Google Scholar
  33. Perkins KA, Grobe JE, Weiss D, Fonte C, Caggiula A (1996b) Nicotine preference in smokers as a function of smoking abstinence. Pharmacol Biochem Behav 55:257–263PubMedGoogle Scholar
  34. Perkins KA, Grobe JE, Caggiula A, Wilson A, Stiller RL (1997a) Acute reinforcing effects of low-dose nicotine nasal spray in humans. Pharmacol Biochem Behav 56:235–241CrossRefPubMedGoogle Scholar
  35. Perkins KA, Sanders M, Amico DD, Wilson A (1997b) Nicotine discrimination and self-administration in humans as a function of smoking status. Psychopharmacology 131:361–370PubMedGoogle Scholar
  36. Perkins KA, Sanders M, Fonte C, Wilson AS, White W, Stiller R, McNamara D (1999) Effects of central and peripheral nicotinic blockade on human nicotine discrimination. Psychopharmacology 142:158–164Google Scholar
  37. Perkins KA, Gerlach D, Broge M, Fonte C, Wilson A (2001a) Reinforcing effects of nicotine as a function of smoking status. Exp Clin Psychopharmacol 9:243–250PubMedGoogle Scholar
  38. Perkins KA, Fonte C, Meeker J, White W, Wilson A (2001b) The discriminative stimulus and reinforcing effects of nicotine in humans following nicotine pretreatment. Behav Pharmacol 12:35–44PubMedGoogle Scholar
  39. Perkins KA, Broge M, Gerlach D, Sanders M, Grobe JE, Cherry C, Wilson AS (2002) Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking. Health Psychol 21:332–339CrossRefPubMedGoogle Scholar
  40. Powell J (1995) Conditioned responses to drug-related stimuli: is context crucial? Addiction 90:1089–1095CrossRefPubMedGoogle Scholar
  41. Pullan RD, Rhodes J, Ganesh S, Mani V, Morris JS, Williams GT, Newcombe RG, Russell MAH, Feyerabend C, Thomas GAO, Sawe U (1994) Transdermal nicotine for active ulcerative colitis. N Engl J Med 330:811–815Google Scholar
  42. Robinson JH, Pritchard WS (1992) The role of nicotine in tobacco use. Psychopharmacology 108:397–407PubMedGoogle Scholar
  43. Rose JE (1996) Nicotine addiction and treatment. Annu Rev Med 47:493–507CrossRefPubMedGoogle Scholar
  44. Rose JE, Behm F, Levin ED (1993) Role of nicotine dose and sensory cues in the regulation of smoke intake. Pharmacol Biochem Behav 44:891–900PubMedGoogle Scholar
  45. Rose JE, Behm FM, Westman EC, Johnson M (2000) Dissociating nicotine and nonnicotine components of cigarette smoking. Pharmacol Biochem Behav 67:71–81Google Scholar
  46. Rose JE, Behm FM, Westman EC, Bates JE (2003) Mecamylamine acutely increases human intravenous nicotine self-administration. Pharmacol Biochem Behav 76:307–313CrossRefPubMedGoogle Scholar
  47. Shahan TA, Bickel WK, Madden GJ, Badger GJ (1999) Comparing the reinforcing efficacy of nicotine containing and de-nicotinized cigarettes: a behavioral economic analysis. Psychopharmacology 147:210–216PubMedGoogle Scholar
  48. Shahan TA, Bickel WK, Badger GJ, Giordano LA (2001) Sensitivity of nicotine-containing and de-nicotinized cigarette consumption to alternative non-drug reinforcement: a behavioral economic analysis. Behav Pharmacol 12:277–284PubMedGoogle Scholar
  49. Silagy C, Lancaster T, Stead L, Mant D, Fowler G (2003) Nicotine replacement therapy for smoking cessation (Cochrane Review). The Cochrane Library, Issue 2. Update Software, OxfordGoogle Scholar
  50. Soria R, Stapleton J, Gilson SF, Sampson-Cone A, Henningfield JE, London ED (1996) Subjective and cardiovascular effects of intravenous nicotine in smokers and non-smokers. Psychopharmacology 128:221–226Google Scholar
  51. Stolerman IP, Jarvis MJ (1995) The scientific case that nicotine is addictive. Psychopharmacology 117:2–10PubMedGoogle Scholar
  52. Swedberg MDB, Henningfield JE, Goldberg SR (1988). Evidence of nicotine dependency from animal studies: Self-administration, tolerance and withdrawal. In: Russell MAH, Stolerman IP, Wannacott S (eds) Nicotine: actions and medical implications. Oxford University Press, Oxford (cf. US Department of Health and Human Services, 1988)Google Scholar
  53. Tobacco Advisory Group of The Royal College of Physicians (2000) Nicotine addiction in Britain. Royal College of Physicians, LondonGoogle Scholar
  54. US Department of Health and Human Services. Nicotine Addiction: a Report of the Surgeon General. DHHS Publication Number (CDC) 88-8406. 1988. Rockville, Md.: Office on Smoking and Health, US Department of Health and Human Services, Office of the Assistant Secretary for HealthGoogle Scholar
  55. Warburton DM (1995) The functional conception of nicotine use. In: Clarke PBS, Quik M, Adlkofer F, Thurau K (eds) Effects of nicotine on biological systems 2. Birkhauser Verlag, Basel Boston Berlin, pp 257–264Google Scholar
  56. Wen HL, Ho WK (1982) Suppression of withdrawal symptoms by dynorphin in heroin addicts Eur J Pharmacol 82:183–186CrossRefGoogle Scholar
  57. West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A (2000) A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology 149:198–202Google Scholar
  58. West R, Hajek P, Nilsson F, Foulds J, May S, Meadows A (2001) Individual differences in preferences for and responses to four nicotine replacement products. Psychopharmacology 153:225–230CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of PsychologyTel Aviv UniversityTel AvivIsrael
  2. 2.The Academic College of Tel Aviv-YafoTel AvivIsrael

Personalised recommendations