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Caffeine as an analgesic adjuvant

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Abstract

Caffeine is a ubiquitous substance. From a historical standpoint, caffeine is one of the oldest substances consumed by man in the form of coffee beans, teas, guanara beans and mate. Caffeine is commonly found in many analgesic products as an adjuvant. Caffeine is almost completely absorbed in the GI tract. Since caffeine is lipid soluble, it is rapidly absorbed into the brain where it becomes active within 6-8 min. Caffeine has some analgesic properties itself and because of its rapid absorption and distribution, is useful as an adjuvant in combination analgesic medications. Because of the wide availability in beverages and medications, concerns regarding overuse resulting in caffeinism, dependence, habituation and addiction have been raised. Extensive review of the literature reveals that occurrence of these conditions resulting from the use of caffeine is minimal and, therefore, caffeine is effective and safe as an analgesic adjuvant.

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REFERENCES

  • Arnaud, M. J. (1987). The pharmacology of caffeine, Prog. Drug Res. 31, 273–313.

    Google Scholar 

  • Barone, J. J. and Roberts, H. (1984). Human consumption of caffeine, in: Caffeine: perspectives from recent research, P. B. Dews (Ed.), pp. 59–73. Springer, Heidelberg.

    Google Scholar 

  • Baumgartner, C., et al. (1989). Longterm prognosis of analgesic withdrawal in patients with drug-induced headaches, Headache 29, 510–514.

    Google Scholar 

  • Booth, D. A., French, J. A., Wainwright, C. J., et al. (1992). Personal benefits from post-ingestional actions of dietary constituents, Proc. Nutr. Soc. 51, 335–341.

    Google Scholar 

  • Booy, R. H. (1972). Pijnbestrijding met eenvoodige anagetica in de tandheelkunde, Ned. Tijdschr. Tanheelkd. 79, 69–75.

    Google Scholar 

  • Dews, P. B., Curtis, G. L., Hanford, K. J., et al. (1999). The frequency of caffeine withdrawal in a population-based survey and in a controlled, blinded experiment, Clin. Pharmacol. 39, 1–12.

    Google Scholar 

  • Diener, H. C., Gerber, W. D., Geiselhart, S., et al. (1988). Short and long-term effects of withdrawal therapy in drug-induced headache, in: Drug-induced Headache, H. C. Diener and M. Wilkinson (Eds), pp. 133–142. Springer-Verlag, Berlin.

    Google Scholar 

  • Driesbach, R. H. and Pfeiffer, C. (1943). Caffeine withdrawal headache, J. Lab. Clin. Med. 28, 1212–1219.

    Google Scholar 

  • Eddy, N. B. and Downs, A. W. (1928). Tolerance and cross-tolerance in the human subject to the diuretic effect of caffeine, theobromine and theophylline, J. Pharmacol. Exp. Ther. 33, 167–174.

    Google Scholar 

  • Evans, S. M. and Griffiths, R. R. (1992). Caffeine tolerance and choice in humans, Psychopharmacology 108, 51–59.

    Google Scholar 

  • Fredholm, B. B. (1995). Astra Award Lecture. Adenosine, adenosine receptors and the actions of caffeine, Pharmacol. Toxicol. 76, 93–101.

    Google Scholar 

  • Fredholm, B. B., Hedqvist, P. and Vernet, L. (1978). Effect of theophylline and other drugs on rabbit renal cyclic nucleotide phosphodiesterase, 5′-nucleotidase and adenosine deaminase, Biochem. Pharmacol. 27, 2845–2850.

    Google Scholar 

  • Fredholm, B. B. and Lindgren, E. (1983). Inhibition of soluble 5′-nucleotidase from rat brain by different xanthine derivatives, Biochem. Pharmacol. 32, 2832–2834.

    Google Scholar 

  • Fredholm, B. B., Battig, K., Holmen, J., et al. (1999). Actions of caffeine in the brain with special reference to factors that contribute to its widespread use, Pharmacol. Rev. 51, 83–133.

    Google Scholar 

  • French, J. A., Wainwright, C. J. and Booth, D. A. (1994). Caffeine and mood: individual differences in low-dose caffeine sensitivity, Appetite 22, 277–279.

    Google Scholar 

  • Gilbert, R. M., Marshman, J. A., Schweider, M., et al. (1976). Caffeine content of beverages as consumed, Can. Med. Assocn J. 114, 205–207.

    Google Scholar 

  • Goldstein, A. and Kaizer, S. (1969a). Psychotropic effects of caffeine in man. III. A questionnaire survey of coffee drinking and its effects in a group of housewives, Clin. Pharmacol. Ther. 10, 477–488.

    Google Scholar 

  • Goldstein, A., Kaizer, S. and Whitby, O. (1969b). Psychotropic effects of caffeine in man. IV. Quantitative and qualitative differences associated with habituation to coffee, Clin. Pharmacol. Ther. 10, 489–497.

    Google Scholar 

  • Greden, J. F., Victor, B. S., Fontaine, P., et al. (1980). Caffeine-withdrawal headache: a clinical profile, Psychosomatics 21 (5), 411–418.

    Google Scholar 

  • Griffiths, R. R. and Mumford, G. K. (1995). Caffeine — a drug of abuse? in: Psychopharmacology: the fourth generation of progress, F. E. Bloom and D. J. Kupfer (Eds), pp. 1699–1713. Raven Press, New York.

    Google Scholar 

  • Griffiths, R. R. and Woodson, P. P. (1988). Reinforcing effects of caffeine in humans, J. Pharmacol. Exp. Ther. 246, 21–29.

    Google Scholar 

  • Griffiths, R. R., Bigelow, G. E. and Liebson, I. A. (1989). Reinforcement effects of caffeine in coffee and capsules, J. Exp. Anal. Behavior 52, 127–140.

    Google Scholar 

  • Griffiths, R. R., Evans, S. M., Heishman, S. J., et al. (1990). Low-dose caffeine physical dependence in humans, J. Pharmacol. Exp. Ther. 255, 1123–1132.

    Google Scholar 

  • Headache Classification Committee of the International Headache Society (1988). Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain, Cephalgia 8, 9–96.

    Google Scholar 

  • Höfer, L. and Bättig, K. (1994a). Cardiovascular, behavioral, and subjective effects of caffeine under field conditions, Pharmacol. Biochem. Behav. 48, 899–908.

    Google Scholar 

  • Höfer, L. and Bättig, K. (1994b). Psychophysiological effects of switching to caffeine tablets or decaffeinated coffee under field conditions, Pharmacopsychoecologia 7, 169–177.

    Google Scholar 

  • Hughes, J. R. (1992). Clinical importance of caffeine withdrawal, N. Engl. J. Med. 327, 1160–1161.

    Google Scholar 

  • Hughes, J. R., Higgins, S. T., Bickel, W. K., et al. (1991). Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers, Arch. Gen. Psychiatry 48, 611–617.

    Google Scholar 

  • Hughes, J. R., Oliveto, A. H., Bickel, W. K., et al. (1993). Caffeine self-administration and withdrawal: incidence, individual differences and interrelationships, Drug Alcohol Dependence 32, 239–246.

    Google Scholar 

  • Kaube, H., May, A., Pfaffenrath, V., et al. (1994). Sumatriptan misuse in daily chronic headache, Brit. Med. J. 308, 1573.

    Google Scholar 

  • Lane, J. D. (1997). Effects of brief caffeinated-beverage deprivation on mood, symptoms, and psychomotor performance, Pharmacol. Biochem. Behav. 58, 203–208.

    Google Scholar 

  • Laska, E. M., Sunshine, A., Mueller, F., et al. (1984). Caffeine as an analgesic adjuvant, J. Amer. Med. Assocn 251, 1711–1718.

    Google Scholar 

  • Micieli, G., Manzoni, G. C., Granella, F., et al. (1988). Clinical and epidemiological observations on drug abuse in headache patients, in: Drug-induced Headache, H. C. Diener and M. Wilkinson (Eds), pp. 20–28. Springer-Verlag, Berlin.

    Google Scholar 

  • Migliardi, J. R., Arrelino, J. J., Friedman, M., et al. (1994). Caffeine as an analgesic adjuvant in tension headache, Clin. Pharmacol. Ther. 56, 576–586.

    Google Scholar 

  • Misra, A. L., Pontani, N. L., Vadlamani (1985). Potentiation of morphine analgesia by caffeine, Brit. J. Pharmacol. 84, 789–792.

    Google Scholar 

  • Mumford, G. K., Neill, D. B. and Holtzmann, S. G. (1988). Caffeine elevates reinforcement threshold for electrical brain stimulation: tolerance and withdrawal changes, Brain Res. 459, 163–167.

    Google Scholar 

  • Nehlig, A. (1999). Are we dependent upon coffee and caffeine? A review on human and animal data, Neurosci. Biobehav. Rev. 23, 563–576.

    Google Scholar 

  • Nehlig, A. and Debry, G. (1994). Effects of coffee on the central nervous system, in: Coffee and Health, G. Debry (Ed.), pp. 157–249. Libbey, London.

    Google Scholar 

  • Nehlig, A., Lucighnani, G., Kadekaro, M., et al. (1984). Effects of accute administration of caffeine on local cerebral glucose utilization in the rat, Eur. J. Pharmacol. 101, 91–100.

    Google Scholar 

  • Nehlig, A., Daval, J. L., Boyet, S., et al. (1986). Comparative effects of acute and chronic administration of caffeine on local glucose utilization in the conscious rat, Eur. J. Pharmacol. 129, 29–103.

    Google Scholar 

  • O' Brien, C. P. (1996). Is there an abuse potential for caffeine-containinganalgesic combinations? in: Advances in the management of acute pain. International Congress and Symposium series 218, A. Holtz (Ed.), pp. 119–127. Royal Society of Medicine Press Limited, London.

    Google Scholar 

  • Pontieri, F. E., Tanda, G. and Dichiara, G. (1995). Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the 'shell’ as compared with the ‘core’ of the rat nucleus accumbens, Proc. Natl. Acad. Sci. USA 92, 12304–12308.

    Google Scholar 

  • Rapoport, A. M., Stang, P., Gutterman, D. L., et al. (1996). Analgesic rebound headache in clinical practice: Data from a physician survey, Headache 36, 14–19.

    Google Scholar 

  • Richardson, N. J., Rogers, P. J., Elliman, N. A., et al. (1995). Mood and performance effects of caffeine in relation to acute and chronic caffeine deprivation, Pharmacol. Biochem. Behavior 52, 313–320.

    Google Scholar 

  • Rogers, P. J. and Richardson, N. J. (1993). Why do we like drinks that contain caffeine? Trends Food Sci. Technol. 4, 108–111.

    Google Scholar 

  • Rogers, P. J., Richardson, N. J. and Dernoncourt, C. (1995). Caffeine use: is there a net benefit for mood and psychomotor performance? Neuropsychobiology 31, 195–199.

    Google Scholar 

  • Ross, G. W., Abbott, R. G., Petrovitch, H., et al. (2000). Association of coffee and caffeine intake with the risk of Parkinson disease, J. Amer. Med. Assocn 283 (20), 2674–2679.

    Google Scholar 

  • Rubin, A. and Winter, L. (1984). A double-blindrandomized study of an aspirin/ caffeine combination versus acetaminophen/ aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain, J. Int. Med. Res. 12, 338.

    Google Scholar 

  • Sawynok, J. and Yaksh, T. L. (1993). Caffeine as an analgesic adjuvant: a review of pharmacology and mechanisms of action, Pharmacol. Rev. 45 (1), 43–85.

    Google Scholar 

  • Scholz, E., Diener, H. C. and Geiselhart, S. (1988). Drug-induced headache — does a critical dosage exist? in: Drug-induced Headache, H. C. Diener and M. Wilkinson (Eds), pp. 29–43. Springer-Verlag, Berlin.

    Google Scholar 

  • Shuh, K. J. and Griffiths, R. R. (1997). Caffeine reinforcement: the role of withdrawal, Psychopharmacology 130, 320–326.

    Google Scholar 

  • Silverman, K., Evans, S. M., Strain, E. C., et al. (1992). Withdrawal syndrome after the double-blind cessation of caffeine consumption, New Engl. J. Med. 327, 1109–1114.

    Google Scholar 

  • Silverman, K., Mumford, G. K. and Griffiths, R. R. (1994). Enhancing caffeine reinforcement by behavioral requirements following drug ingestion, Psychopharmacology 114, 424–432.

    Google Scholar 

  • Stern, K. N., Chait, L. D. and Johanson, C. E. (1989). Reinforcing and subjective effects of caffeine in normal human volunteers, Psychopharmacology 98, 81–88.

    Google Scholar 

  • Strain, E. C., Mumford, G. K., Silverman, K., et al. (1994). Caffeine dependence syndrome. Evidence from case histories and experimental evaluations, J. Amer. Med. Assocn 272, 1043–1048.

    Google Scholar 

  • Strain, E. C. and Griffiths, R. R. (1995). Caffeine dependence: fact or fiction? J. Roy. Soc. Med. 88, 437–440.

    Google Scholar 

  • Wallenstein, S. (1975). Analgesic studies of aspirin in cancer patients, Proceedings of the Aspirin Symposium. Pp. 5–10.

  • Ward, N., Whitney, C., Avery, D., et al. (1991). The analgesic effects of caffeine in headache, Pain 44, 151–155.

    Google Scholar 

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  1. San Francisco Clinical Research Center, 909 Hyde Street, Suite 322, San Francisco, CA, 94109, USA

    Jerome Goldstein

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Goldstein, J. Caffeine as an analgesic adjuvant. Inflammopharmacology 9, 51–61 (2001). https://doi.org/10.1163/156856001300248326

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