The scientific case that nicotine is addictive

Abstract

Despite the wide-ranging and authoritative 1988 review by the US Surgeon General, views questioning the addictiveness of nicotine contine to be expressed in some quarters. This lack of complete consensus is not unexpected, since no universally agreed scientific definition of addiction exists. In this paper we briefly consider a number of lines of evidence from both the human and animal literature bearing on the addictiveness of nicotine. Patterns of use by smokers and the remarkable intractability of the smoking habit point to compulsive use as the norm. Studies in both animal and human subjects have shown that nicotine can function as reinforcer, albeit under a more limited range of conditions than with some other drugs of abuse. In drug discrimination paradigms there is some cross-generalisation between nicotine on the one hand, and amphetamine and cocaine on the other. A well-defined nicotine withdrawal syndrome has been delineated which is alleviated by nicotine replacement. Nicotine replacement also enhances outcomes in smoking cessation, roughly doubling success rates. In total, the evidence clearly identifies nicotine as a powerful drug of addiction, comparable to heroin, cocaine and alcohol.

This is a preview of subscription content, log in to check access.

References

  1. American Psychiatric Association, (1987) Diagnostic and statistical manual of mental disorders, 3rd edn. Washington DC

  2. Ando K, Yanagita T (1978) The discriminative stimulus properties of intravenously administered cocaine in rhesus monkeys. In: Colpaert FC, Rosecrans JA (eds) Stimulus properties of drugs: ten years of progress. Elsevier/North-Holland, Amsterdam, pp 125–136

    Google Scholar 

  3. Ator NA, Griffiths PR (1981) Intravenous self-administration of nicotine in the baboon. Fed Proc 40:298

    Google Scholar 

  4. Babor TF (1990) Social, scientific and medical issues in the definition of alcohol and drug dependence. In: Edwards G, Lader MH (eds) The nature of drug dependence. Oxford University Press, Oxford, pp 19–36

    Google Scholar 

  5. Benwell MEM, Balfour DJK (1992) The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol 105:849–856

    PubMed  Google Scholar 

  6. Bigelow G, Rand CS, Gross J, Barling TA, Gotlieb SH (1963) Smoking cessation and relapse among cardiac patients. In: Tims FM, Leubefeld CG (eds) Relapse and recovery in drug abuse. NIDA Research Monograph 72. Department of Health and Human Services, Rockville, Maryland

    Google Scholar 

  7. Brazell MP, Mitchell SN, Joseph MH, Gray JA (1990) Acute administration of nicotine increases thein vivo extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid and ascorbic acid preferentially in the nucleus accumbens of the rat: comparison with caudate-putamen. Neuropharmacology 29:1177–1185

    Article  PubMed  Google Scholar 

  8. Chait LD, Johanson C-E (1988) Discriminative stimulus effects of caffeine and benzphetamine in amphetamine trained volunteers. Psychopharmacology 96:302–308

    Google Scholar 

  9. Chance WT, Murfin D, Krynock GM, Rosecrans JA (1977) A description of the nicotine stimulus and tests of its generalization to amphetamine. Psychopharmacology 55:19–26

    Article  Google Scholar 

  10. Clarke PBS, Kumar R (1984) Effects of nictonie andd-amphetamine on intracranial self-stimulation in a shuttlebox test in rats. Psychopharmacology 84:109–114

    Article  PubMed  Google Scholar 

  11. Cohen S, Lichtenstein E, Prochaska JO et al. (1989) Debunking myths about self-quitting. Am Psychol 44:1355–1365

    Article  PubMed  Google Scholar 

  12. Corrigall WA, Herling S, Coen KM (1989) Evidence for a behavioral deficit during withdrawal from chronic nicotine treatment. Pharmacol Biochem Behav 33:559–562

    Google Scholar 

  13. Corrigall WA, Franklin KBJ, Coen KM, Clarke PBS (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology 107:285–289

    PubMed  Google Scholar 

  14. Davison G, Duffy M (1982) Smoking habits of long-term survivors of surgery for lung cancer. Thorax 37:331–333

    PubMed  Google Scholar 

  15. de la Garza R, Johanson CE (1983) The discriminative stimulus properties of cocaine in the rhesus monkey. Pharmacol Biochem Behav 19:145–148

    Article  PubMed  Google Scholar 

  16. de la Garza R, Johanson CE (1985) Discriminative stimulus properties of cocaine in pigeons. Psychopharmacology 85:23–30

    Article  PubMed  Google Scholar 

  17. Druhan JP, Fibiger HC, Phillips AG (1991) Influence of some drugs of abuse on the discriminative stimulus properties of amphetamine. Behav Pharmacol 2:391–403

    PubMed  Google Scholar 

  18. Fagerström KO, Schneider NG, Lunell E (1993) Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology 111:271–277

    Article  PubMed  Google Scholar 

  19. Foulds J (1993) Does nicotine replacement therapy work? Addiction 88:1473–1478

    PubMed  Google Scholar 

  20. Gauvin DV, Harland RD, Michaelis RC, Holloway FA (1989) Caffeine phenylethylamine combinations mimic the cocaine discriminative cue. Life Sci 44:67–73

    Article  PubMed  Google Scholar 

  21. Gawin FH (199) Cocaine addiction: psychology and neurophysiology. Science 251:1580–1586

    Google Scholar 

  22. Goddard E (1990) Why children start smoking. HMSO, London

    Google Scholar 

  23. Goldberg SR (1973) Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection ord-amphetamine injection in the squirrel monkey. J Pharmacol Exp Ther 186:18–30

    PubMed  Google Scholar 

  24. Goldberg SR (1975) Stimuli associated with drug injections as events that control behavior. Pharmacol Rev 27:325–340

    PubMed  Google Scholar 

  25. Goldberg SR, Spealman RD (1982) Maintenance and suppression of behavior by intravenous nicotine injections in squirrel monkeys. Fed Proc 41:216–220

    PubMed  Google Scholar 

  26. Goldberg SR, Spealman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575

    PubMed  Google Scholar 

  27. Goudie AJ, Leathley MJ (1993) Drug discrimination assays. In: Sahgal A (ed) Behavioural neuroscience. Open University Press, Walton Hall, Bucks. pp 145–167

    Google Scholar 

  28. Griffiths RR, Brady JV, Bradford LD (1979) Predicting the abuse liability of drugs with animal drug self-administration procedures: psychomotor stimulants and hallucinogens. In: Thompson T, Dews PB (eds) Advances in behavioral pharmacology, Vol 2. Academic Press, New York, pp 162–208

    Google Scholar 

  29. Gross J, Stitzer ML (1989) Nicotine replacement: ten-week effects on tobacco withdrawal symptoms. Psychopharmacology 98:334–341

    Article  PubMed  Google Scholar 

  30. Harland RD, Gauvin DV, Michaelis RC, Carney JM, Seale TW, Holloway FA (1989) Behavioral interaction between cocaine and caffeine: a drug discrimination analysis in rats. Pharmacol Biochem Behav 32:1017–1023

    Google Scholar 

  31. Harris CM, Emmett-Oglesby MW, Robinson NG, Lal H (1986) Withdrawal from chronic nicotine substitutes partially for the interoceptive stimulus produced by pentylenetetrazol (PTZ). Psychopharmacology 90:85–89

    Google Scholar 

  32. Hatsukami DK, Gust SW, Keenan RM (1987) Physiologic and subjective changes from smokeless tobacco withdrawal. Clin Pharmacol Ther 41:103–107

    PubMed  Google Scholar 

  33. Henningfield JE, Goldberg SR (1984) Stimulus properties of nicotine in animals and human volunteers: a review. In: Seiden LS, Balster RL (eds). Behavioral pharmacology: the current status. Alan R Liss, New York, pp 433–449

    Google Scholar 

  34. Himbury S, West R (1984) Smoking habits after laryngectomy. BMJ 291:514–515

    Google Scholar 

  35. Hughes JR (1992) Tobacco withdrawal in self-quitters. J Consult Clin Psychol 60:689–697

    Article  PubMed  Google Scholar 

  36. Hughes JR (1993) Smoking is a drug dependence: a reply to Robinson and Pritchard. Psychopharmacology 113:282–283

    Article  PubMed  Google Scholar 

  37. Hughes JR, Hatsukami D (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43:289–294

    PubMed  Google Scholar 

  38. Hughes JR, Hatsukami DK, Pickens RW, Krahn D, Malin S, Luknic A (1984) Effect of nicotine on the tobacco withdrawal syndrome. Psychopharmacology 83:82–87

    Article  PubMed  Google Scholar 

  39. Hughes JR, Hatsukami DK Skoog K (1986) Physical dependence on nicotine gum: a placebo substitution trial JAMA 255:3277–3279

    Article  PubMed  Google Scholar 

  40. Hughes JR, Higgins ST, Hatsukami DK (1990) Effects of abstinence from tobacco: a critical review. In: Kozlowski LT, Annis HM, Cappell HD, Glaser FB, Goodstadt MS, Israel Y, Kalant H, Sellers EM, Vingilis J (eds) Research advances in alcohol and drug problems, Vol 10. Plenum, New York, pp 317–398

    Google Scholar 

  41. Hughes JR, Gulliver SB, Fenwick JW, Valliere WA, Cruser K, Pepper S, Shea P, Solomon LJ, Flynn BS (1992) Smoking cessation among self-quitters. Health Psychol 11:331–334

    Article  PubMed  Google Scholar 

  42. Hunt WA, Bespalec DA (1974) An evaluation of current methods of modifying smoking behaviour. J Clin Psychol 30:431–438

    PubMed  Google Scholar 

  43. Hunt WA, Barnett LW, Branch LG (1971) Relapse rates in addiction programs. J Clin Psychol 27:455–456

    PubMed  Google Scholar 

  44. Huston-Lyons D, Kornetsky C (1992) Effects of nicotine on the threshold for rewarding brain stimulation in rats. Pharmacol Biochem Behav 41:755–759

    Article  PubMed  Google Scholar 

  45. Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats. Eur J Pharmacol 132:337–338

    Google Scholar 

  46. Jaffe JH (1990) Tobacco smoking and nicotine dependence. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology: molecular, cellular and behavioural aspects. Oxford Science Publications, Oxford, pp 1–37

    Google Scholar 

  47. Jarvis MJ, Raw M, Russell MAH, Feyerabend C (1982) Randomised controlled trial of nicotine chewing-gum. BMJ 285:537–540

    PubMed  Google Scholar 

  48. Johanson CE (1978) Drugs as reinforcers. In: Blackman DE, Sanger DJ (eds) Contemporary research in behavioral pharmacology. Plenum, New York, pp 325–390

    Google Scholar 

  49. Jones RT (1992) What we have learned from nicotine, cocaine and marijuana about addiction. In: O'Brien CP, Jaffe JH (eds) Addictive states. Res Publ Assoc Res Nerv Ment Dis Vol 70. Raven, New York, pp 109–122

    Google Scholar 

  50. Karler R, Calder LD, Chaudry IA, Turkanis SA (1989) Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801. Life Sci 45:599–606

    Article  PubMed  Google Scholar 

  51. Ksir C, Hakan RL, Kellar KJ (1987) Chronic nicotine and locomotor activity: influences of exposure dose and test dose. Psychopharmacology 92:25–29

    Article  PubMed  Google Scholar 

  52. Levin ED, Rose JE (1990) Anticholinergic sensitivity following chronic nicotine administration as measured by radial-arm maze performance in rats. Behav Pharmacol 1:511–520

    PubMed  Google Scholar 

  53. Malin DH, Lake JR, Newlin-Maultsby P, Roberts LK, Lanier JG, Carter VA, Cunningham JS, Wilson OB (1992) Rodent model of nicotine abstinence syndrome. Pharmacol Biochem Behav 43:779–784

    Article  PubMed  Google Scholar 

  54. Mariathasan EA, Stolerman IP (1992) Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures. Psychopharmacology 109:99–106

    Article  PubMed  Google Scholar 

  55. Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226:817–825

    PubMed  Google Scholar 

  56. Marks MJ, Stitzel JA, Collins AC (1985) Time course study of the effects of chronic nicotine infusion on drug responses and brain receptors. J Pharmacol Exp Ther 235:619–628

    PubMed  Google Scholar 

  57. Modrow HE, Holloway FA, Carney JM (1981) Caffeine discrimination in the rat. Pharmacol Biochem Behav 14:683–688

    Article  PubMed  Google Scholar 

  58. Mumford GK, Holtzman SG (1991) Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. J Pharmacol Exp Ther 258:857–865

    PubMed  Google Scholar 

  59. NOP Omnibus Services (1992) Smoking habits 1991: a report prepared for the Department of Health. Department of Health, London

    Google Scholar 

  60. Risner ME, Goldberg SR (1983) A comparison of nicotine and cocaine self-administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion. J Pharmacol Exp Ther 224:319–326

    PubMed  Google Scholar 

  61. Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787

    Google Scholar 

  62. Robins LN (1993) Vietnam veterans' rapid recovery from heroin addiction: a fluke or normal expectation. Addiction 88:1041–1054

    PubMed  Google Scholar 

  63. Robinson JH, Pritchard WS (1992) The role of nicotine in tobacco use. Psychopharmacology 108:397–407

    Article  PubMed  Google Scholar 

  64. Rowell PP, Carr LA, Garner AC (1987) Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens. J Neurochem 49:1449–1454

    PubMed  Google Scholar 

  65. Russell MAH (1974) The smoking habit and its classification. Practitioner 212:791–800

    PubMed  Google Scholar 

  66. Russell MAH (1986) Conceptual Framework for nicotine substitution. In: Ockene JK (ed) The pharmacologic treatment of tobacco dependence: Proceedings of the World Congress. Cambridge, Massachusetts, Harvard University Institute for the Study of Smoking Behavior and Policy, pp 90–107

    Google Scholar 

  67. Russell MAH, Stapleton J, Feyerbend C, Wiseman SM, Gustavsson G (1993) Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. BMJ 306:1308–1312

    PubMed  Google Scholar 

  68. Schaefer GJ, Michael RP (1986) Task-specific effects of nicotine in rats. Intracranial self-stimulation and locomotor activity. Neuropharmacology 25:125–131

    Article  PubMed  Google Scholar 

  69. Schuster CR, Thompson T (1969) Self-administration of and behavioral dependence on drugs. Annu Rev Pharmacol 9:483–502

    Article  PubMed  Google Scholar 

  70. Schwartz, JL (1987) Review and evaluation of smoking cessation methods: the United States and Canada 1978–985. US Department of Health and Human Services, Washington DC

    Google Scholar 

  71. Shiffman S (1989) Tobacco chppers — individual differences in tobacco dependence. Psychopharmacology 97:539–547

    Google Scholar 

  72. Shoaib M, Stolerman IP (1992) MK801 attenuates behavioural adaptation to chronic nicotine administration in rats. Br J Pharmacol 105:514–515

    PubMed  Google Scholar 

  73. Shoaib M, Benwell MEM, Akbar MT, Stolerman IP, Balfour DJK (1994) Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists. Br J Pharmacol 111:1073–1080

    PubMed  Google Scholar 

  74. Silverman PB, Schultz KA (1989) Comparison of cocaine and procaine discriminative stimuli. Drug Dev Res 16:427–433

    Article  Google Scholar 

  75. Smyth, M, Browne, F (1992) General household survey 1990. HMSO, London

    Google Scholar 

  76. Stolerman IP (1987) Psychopharmacology of nicotine: stimulus effects and receptor mechanisms. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, Vol. 19. Plenum, New York, pp 421–465

    Google Scholar 

  77. Stolerman IP (1989) Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Psychopharmacology 97:131–138

    Article  Google Scholar 

  78. Stolerman IP, Garcha HS, Pratt JA, Kumar R (1984) Role of training dose in discrimination of nicotine and related compounds by rats. Psychopharmacology 84:413–419

    Article  Google Scholar 

  79. Sutherland G, Stapleton J, Russell MAH, Jarvis MJ, Hajek P, Belcher M, Feyerabend C (1992) Randomised controlled trial of nicotine nasal spray in smoking cessation. Lancet 340:324–329

    Article  PubMed  Google Scholar 

  80. Swedberg MDB, Henningfield JE, Goldberg SR (1990) Nicotine dependency: animal studies. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology: molecular, cellular and behavioural aspects. Oxford Science Publications, Oxford, pp 38–76

    Google Scholar 

  81. Tonnesen P, Norregaard J, Simonsen K, Säwe U (1991) A doubleblind trial of a 16-hour nicotine patch in smoking cessation. N Engl J Med 325:311–315

    PubMed  Google Scholar 

  82. Tonnesen P, Norregaard J, Mikkelsen K, Jorgensen S, Nilsson F (1993) A double-blind trial of a nicotine inhaler for smoking cessation. JAMA 269:1268–1271

    Article  PubMed  Google Scholar 

  83. Transdermal Nicotine Study Group (1991) Transdermal nicotine for smoking cessation: six-month results from two multicenter controlled clinical trials. JAMA 266:3133–3138

    Google Scholar 

  84. Trujillo KA, Akil H (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:85–87

    Google Scholar 

  85. US Department of Health, Education and Welfare (1964) Smoking and Health. Report of the Advisory Committee to the Surgeon General of the Public Health Service. US Department of Health, Education and Welfare, Washingtone, DC

    Google Scholar 

  86. US Department of Health and Human Services (1988) The health consequences of smoking: nicotine addiction. A Report of the Surgeon General. Office on Smoking and Health, Maryland

    Google Scholar 

  87. Warburton DM (1989) Is nicotine use an addiction? Psychologist 4:166–170

    Google Scholar 

  88. Warburton DM (1990) Heroin, cocaine and now nicotine. In: Warburton DM (ed) Addiction controversies. Harwood Academic Publishers, Switzerland, pp 21–35

    Google Scholar 

  89. West RJ (1992a) Nicotine addiction: a re-analysis of the arguments. Psychopharmacology 108:408–410

    Article  PubMed  Google Scholar 

  90. West R (1992b) The “nicotine replacement paradox” in smoking cessation: how does nicotine gum really work? Br J Addict 87:165–167

    PubMed  Google Scholar 

  91. West RJ, Russell MAH (1985) Effects of withdrawal from long-term nicotine gum use. Psychol Med 15:891–893

    PubMed  Google Scholar 

  92. West RJ, Jarvis MJ, Russell MAH Carruthers ME, Feyerbend C (1984) Effect of nicotine replacement on the cigarette withdrawal syndrome. Br J Addict 79:215–219

    PubMed  Google Scholar 

  93. West RJ, Hajek P, Belcher M (1989) Severity of withdrawal symptoms as a predictor of outcome of an attempt to quit smoking. Psychol Med 98:331–334

    Google Scholar 

  94. World Health Organization (1969) World Health Organization Technical Report Series No. 407. WHO, Geneva

    Google Scholar 

  95. World Health Organization (1978) International classification of diseases, 9th edn. WHO, Geneva

    Google Scholar 

  96. Young AM, Herling S (1986) Drugs as reinforcers: studies in laboratory animals. In: Goldberg SR, Stolerman IP (eds) Behavioral analysis of drug dependence. Academic Press, Orlando, Florida, pp 9–67

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Stolerman, I.P., Jarvis, M.J. The scientific case that nicotine is addictive. Psychopharmacology 117, 2–10 (1995). https://doi.org/10.1007/BF02245088

Download citation

Key words

  • Tobacco use
  • Nicotine
  • Addiction