Psychopharmacology

, Volume 115, Issue 1–2, pp 1–8 | Cite as

Discriminative stimulus and subjective effects of theobromine and caffeine in humans

  • Geoffrey K. Mumford
  • Suzette M. Evans
  • Barbara J. Kaminski
  • Kenzie L. Preston
  • Christine A. Sannerud
  • Kenneth Silverman
  • Roland R. Griffiths
Original Investigations

Abstract

Theobromine versus placebo discrimination and caffeine versus placebo discrimination were studied in two consecutive experiments in seven volunteers who abstained from methylxanthines. Daily sessions involved PO double-blind ingestion of two sets of capsules sequentially, one of which contained drug and the other placebo. Subjects attempted to identify, and were later informed, which set of capsules contained the drug. In each experiment subjects were exposed to progressively lower doses. Five subjects acquired the theobromine discrimination; the lowest dose discriminated ranged from 100 to 560 mg. All seven subjects acquired the caffeine discrimination; the lowest dose discriminated ranged from 1.8 to 178 mg. A final experiment evaluated subjective effect ratings following 560 mg theobromine, 178 mg caffeine and placebo, which were administered double-blind in capsules once daily, five times each in mixed sequence. Caffeine produced changes in both group and individual ratings (e.g. increased well-being, energy, social disposition and alert). Theobromine did not produce changes in group ratings but changed ratings in some subjects. Across subjects, sensitivity to caffeine discriminative effects in the discrimination experiment correlated significantly with the number and magnitude of caffeine subjective effects in the final experiment. This study documents modest discriminative effects of theobromine in humans, but the basis of the discrimination is unclear. This study suggests that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine.

Key words

Theobromine Caffeine Methylxanthine Cocoa Chocolate Drug discrimination Subjective effects Humans 

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References

  1. Barone JJ, Roberts H (1984) Human consumption of caffeine. In: Dews PB (ed) Caffeine: perspectives from recent research. Springer, Berlin Heidelberg New York, pp 59–73Google Scholar
  2. Batterman RC, Grossman AJ, Dubinsky J, Mouratoff G (1959) Re-evaluation of the usefulness of theobromine calcium gluconate for the management of congestive heart failure and anginal syndrome. Int Rec Med 172:318–323Google Scholar
  3. Beccari E (1936) Massen-vergiftung durch theobromin-derivate. Fühner-Weilands Sammlung von Vergiftungsfällen 7:77–80Google Scholar
  4. Beer B, Chasin M, Clody DE, Vogel JR, Horovitz ZP (1972) Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety. Science 176:428–430Google Scholar
  5. Blumgart HL, Gilligan DR, Levy RC, Brown MG, Volk MC (1934) Action of diuretic drugs: I. Action of diuretics in normal persons. Arch Int Med 54:40–79Google Scholar
  6. Brunk SF, Ferguson RK, Toubes DB, Leaverton PE, Nordschow CD, Wilson WR (1973) A teaching format in clinical pharmacology. Comparison of two xanthines and a placebo. J Clin Pharmacol 13:121–126Google Scholar
  7. Carney JM (1982) Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol 75:451–454Google Scholar
  8. Carney JM, Holloway FA, Modrow HE (1985) Discriminative stimulus properties of methylxanthines and their metabolites in rats. Life Sci 36:913–920Google Scholar
  9. Carney JM, Cao W, Logan L, Rennert OM, Seale TW (1986) Differential antagonism of the behavioral depressant and hypothermic effects of 5′-(N-ethylcarboxamide) adenosine by theobromine. Pharmacol Biochem Behav 25:769–773Google Scholar
  10. Costa PT, Jr, McCrae RR (1985) The NEO personality inventory manual. Psychological Assessment Resources, Inc., Odessa, Fla.Google Scholar
  11. Dorfman LJ, Jarvik ME (1970) Comparative stimulant and diuretic actions of caffeine and theobromine in man. Clin Pharmacol Ther 11:869–872Google Scholar
  12. Fries JH (1978) Chocolate: a review of published reports of allergic and other deleterious effects, real or presumed. Ann Allergy 41:196–207Google Scholar
  13. Gibb CM, Davies PTG, Glover V, Steiner TJ, Rose FC, Sandler M (1991) Chocolate is a migraine-provoking agent. Cephalalgia 11:93–95Google Scholar
  14. Griffiths RR, Mumford GK (1994) Caffeine — a drug of abuse? In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation of progress. Raven, New YorkGoogle Scholar
  15. Griffiths RR, Woodson PP (1988) Reinforcing properties of caffeine: studies in humans and laboratory animals. Pharmacol Biochem Behav 29:419–427Google Scholar
  16. Griffiths RR, Evans SM, Heishman SJ, Preston KL, Sannerud CA, Wolf B, Woodson PP (1990a) Low-dose caffeine discrimination in humans. J Pharmacol Exp Ther 252:970–978Google Scholar
  17. Griffiths RR, Evans SM, Heishman SJ, Preston KL, Sannerud CA, Wolf B, Woodson PP (1990b) Low-dose caffeine physical dependence in humans. J Pharmacol Exp Ther 255:1123–1132Google Scholar
  18. Herz A, Neteler B, Teschemacher HJ (1968) Vergleichende untersuchungen über zentrale wirkungen von xanthinderivaten in hinblick auf deren stoffwechsel und verteilung im organismus. Naunyn Schmiedebergs Arch Pharmakol Exp Pathol 261:486–502Google Scholar
  19. Holtzman SG (1986) Discriminative stimulus properties of caffeine in the rat: noradrenergic mediation. J Pharmacol Exp Ther 239:706–714Google Scholar
  20. Ishay JS, Paniry VA (1979) Effects of caffeine and various xanthines on hornets and bees. Psychopharmacology 65:299–309Google Scholar
  21. Jacob P, III, Wilson M, Benowitz NL (1981) Improved gas chromatographic method for determination of nicotine and cotinine in biologic fluids. J Chromatogr 222:61–70Google Scholar
  22. Katims JJ, Annau Z, Snyder SH (1983) Interactions in the behavioral effects of methylxanthines and adenosine derivatives. J Pharmacol Exp Ther 227:167–173Google Scholar
  23. Kuribara H, Tadokoro S (1992) Behavioral effects of cocoa and its main active compound theobromine: evaluation by ambulatory activity and discrete avoidance in mice. Jpn J Alcohol Drug Depend 27:168–179Google Scholar
  24. Lickint F (1938) Kakaogenuß und kopfschmerz. Deutsche Med Wochenschr 64:1545–1546Google Scholar
  25. Overton DA (1984) State dependent learning and drug discriminations. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, Vol. 18. Plenum, New York London, pp 59–127Google Scholar
  26. Pao EM, Fleming KH, Guenther PM, Mickle SJ (1982) Foods commonly consumed by individuals: amount per day and per eating occasion. US Department of Agriculture, Nutrition Information Service, Home Economic Research Report, SUDOC #A1.87:44Google Scholar
  27. Preston KL, Bigelow GE (1991) Subjective and discriminative effects of drugs. Behav Pharmacol 2:293–313Google Scholar
  28. Raebel MA, Black J (1984) The caffeine controversy: what are the facts? Hosp Pharm 19:257–267Google Scholar
  29. Samele C, Shine PJ, Stolerman IP (1992) Forty years of drug discrimination research: a bibliography for 1951–1991; 10th anniversary edition. Institute of Psychiatry, London (Available from Stolerman IP, Section of Behavioural Pharmacology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK)Google Scholar
  30. Sandler M, Youdim MBH, Hanington E (1974) A phenylethylamine oxidising defect in migraine. Nature 250:335–337Google Scholar
  31. Schuster CR, Johanson CE (1988) Relationship between the discriminative stimulus properties and subjective effects of drugs. In: Colpaert FC, Balster RL (eds) Transduction mechanisms of drug stimuli. Springer, Berlin Heidelberg, pp 161–175Google Scholar
  32. Shively CA, Tarka SM (1984) Methylxanthine composition and consumption patterns of cocoa and chocolate products. In: Spiller GA (ed) The methylxanthine beverages and foods: chemistry, consumption, and health effects. Liss, New York, pp 149–178Google Scholar
  33. Silverman K, Griffiths RR (1992) Low-dose caffeine discrimination and self-reported mood effects in normal volunteers. J Exp Anal Behav 57:91–107Google Scholar
  34. Snyder SH, Katims JJ, Annau Z, Bruns RF, Daly JW (1981) Adenosine receptors and behavioral actions of methylxanthines. Proc Natl Acad Sci USA 78:3260–3264Google Scholar
  35. Spielberger CD, Gorsuch RI, Lushene RE (1970) STAI manual for the state-trait anxiety inventory (“self-evaluation questionnaire”). Consulting Psychologists Press, Palo Alto, Calif.Google Scholar
  36. Sprügel W, Mitznegg P, Heim F (1977) The influence of caffeine and theobromine on locomotive activity and the brain cGMP/cAMP ratio in white mice. Biochem Pharmacol 26:1723–1724Google Scholar
  37. Stavric B (1988) Methylxanthines: toxicity to humans. 3. Theobromine, paraxanthine and the combined effects of methylxanthines. Food Chem Toxicol 26:725–733Google Scholar
  38. Tarka SM (1982) The toxicology of cocoa and methylxanthines: a review of the literature. Crit Rev Toxicol 9:275–312Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Geoffrey K. Mumford
    • 1
  • Suzette M. Evans
    • 2
  • Barbara J. Kaminski
    • 1
  • Kenzie L. Preston
    • 1
    • 3
  • Christine A. Sannerud
    • 1
    • 4
  • Kenneth Silverman
    • 1
    • 3
  • Roland R. Griffiths
    • 1
    • 5
  1. 1.Department of Psychiatry and Behavioral SciencesJohns Hopkins University School of Medicine, Behavioral Biology Research CenterBaltimoreUSA
  2. 2.Clinical Pharmacology Branch, National Institute on Drug Abuse, Addiction Research CenterBaltimoreUSA
  3. 3.Treatment Branch, National Institute on Drug Abuse, Addiction Research CenterBaltimoreUSA
  4. 4.Preclinical Pharmacology Laboratory, National Institute on Drug AbuseAddiction Research CenterBaltimoreUSA
  5. 5.Department of NeuroscienceJohn Hopkins University School of Medicine, Behavioral Biology Research CenterBaltimoreUSA

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