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Behavioral Pharmacology of Caffeine

  • Chapter
Handbook of Substance Abuse

Abstract

Caffeine, a central nervous system (CNS) stimulant, is the most widely used psychotropic drug in the world (Gilbert, 1984). In the United States, more than 85% of adults consume caffeine daily (Gilbert, 1976; Graham, 1978) and the average daily consumption is estimated to be 200 mg (Barone & Roberts, 1984). Caffeine is found in a wide variety of beverages (e.g., coffee, tea, colas), prescription drugs and over-the-counter stimulants, analgesics and cold preparations, and food items such as chocolate. Caffeine has been considered to be a model drug for studying and understanding drugs of abuse (Holtzman, 1990; Rush, Sullivan, & Griffiths, 1995), in part due to caffeine’s widespread use, and because caffeine produces a range of behavioral effects that are common to classic drugs of abuse.

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References

  • Ahlijanian, M. K., and Takemori, A. E. (1986). Cross-tolerance studies between caffeine and (—)-N’-(phenyl isopropyl)-adenosine (PIA) in mice. Life Sciences, 38, 577–588.

    Article  PubMed  CAS  Google Scholar 

  • Ahmad, R. A., and Watson, R. D. (1990). Treatment of pos- tural hypotension. A review. Drugs, 39, 74–85.

    CAS  Google Scholar 

  • American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed., rev.). Washington, DC: Author.

    Google Scholar 

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders ( 4th ed. ). Washington, DC: Author.

    Google Scholar 

  • Ammon, H. P. T., Bieck, P. R., Mandalaz, D., and Verspohl, E. J. (1983). Adaptation of blood pressure to continuous heavy coffee drinking in young volunteers. A double-blind crossover study. British Journal of Clinical Pharmacology, 15, 701–706.

    Article  PubMed  CAS  Google Scholar 

  • Atkinson, J., and Enslen, M. (1976). Self-administration of caffeine by the rat. Arzneimittel-Forschung, 26, 2059–2061.

    PubMed  CAS  Google Scholar 

  • Bairam, A., Boutroy, M. J., Badonnel, Y., and Vert, P. (1987). Theophylline versus caffeine: Comparative effects in treatment of idiopathic apnea in the preterm infant. Journal of Pediatrics, 110, 636–639.

    Article  PubMed  CAS  Google Scholar 

  • Balster, R. L. (1987). Abuse potential evaluation of in- halants. Drug and Alcohol Dependence, 19, 7–15.

    Article  PubMed  CAS  Google Scholar 

  • Barone, J. J., and Roberts, H. (1984). Human consumption of caffeine. In P. B. Dews (Ed.), Caffeine: Perspectives from recent research (pp. 59–73 ). Berlin: Springer-Verlag.

    Google Scholar 

  • Bättig, K. (1985). The physiological effects of coffee consumption. In M. N. Clifford and C. K. Wilson (Eds.), Coffee: Botany, biochemistry and production of beans and beverages (pp. 394–439 ). London: Croom Helm.

    Google Scholar 

  • Bättig, K., and Welzl, H. (1993). Psychopharmacological profile of caffeine. In S. Garattini (Ed.), Caffeine, coffee, and health (pp. 213–253 ). New York: Raven.

    Google Scholar 

  • Bonnet, M. H., and Arand, D. L. (1992). Caffeine use as a model of acute and chronic insomnia. Sleep, 15, 526–536.

    PubMed  CAS  Google Scholar 

  • Boulenger, J. P., and Uhde, T. W. (1982). Biochemical aspects of anxiety. Semaine des Hopitaux, 58, 2573 2579.

    Google Scholar 

  • Boulenger, J. P., Uhde, T. W., Wolff, E. A., Ill, and Post, R. M. (1984). Increased sensitivity to caffeine in patients with panic disorders. Preliminary evidence. Archives of General Psychiatry, 41, 1067–1071.

    CAS  Google Scholar 

  • Boyd, E. M., Dolman, M., Knight, L. M., and Sheppard, E. P. (1965). The chronic oral toxicity of caffeine. Canadian Journal of Physiology and Pharmacology, 43, 995–1007.

    Article  CAS  Google Scholar 

  • Bozarth, M. A. (1987). An overview of assessing drug reinforcement. In M. A. Bozarth (Ed.), Methods of assessing the reinforcing properties of abused drugs (pp. 635–658 ). New York: Springer-Verlag.

    Chapter  Google Scholar 

  • Bruce, M., Scott, N., Shine, P., and Lader, M. (1991). Caffeine withdrawal: A contrast of withdrawal symptoms in normal subjects who have abstained from caffeine for 24 hours and for 7 days. Journal of Psychopharmacology, 5, 129–134.

    Article  PubMed  CAS  Google Scholar 

  • Carney, J. M. (1982). Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. British Journal of Clinical Pharmacology, 75, 451–454.

    Article  CAS  Google Scholar 

  • Carney, J. M., Holloway, E. A., and Modrow, H. E. (1985). Discriminative stimulus properties of methylxanthines and their metabolites in rats. Life Sciences, 36, 913–920.

    Article  PubMed  CAS  Google Scholar 

  • Carroll, M. E. (1987). A quantitative assessment of phencyclidine dependence produced by oral self-administration in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 242, 405–412.

    PubMed  CAS  Google Scholar 

  • Carroll, M. E., Hagen, E. W, Asencio, M., and Hartman Brauer, L. (1989). Behavioral dependence on caffeine and phencyclidine in rhesus monkeys: Interactive effects. Pharmacology, Biochemistry and Behavior, 31, 927–932.

    Article  Google Scholar 

  • Chait, L. D., and Griffiths, R. R. (1983). Effects of caffeine on cigarette smoking and subjective response. Clinical Pharmacology and Therapeutics, 34, 612–622.

    Article  PubMed  CAS  Google Scholar 

  • Chait, L. D., and Johanson, C. E. (1988). Discriminative stimulus effects of caffeine and benzphetamine in amphetamine-trained volunteers. P ychopharmacologv, 96, 302–308.

    Article  CAS  Google Scholar 

  • Charney, D. S., Heninger, G. R., and Jatlow, P. I. (1985). Increased anxiogenic effects of caffeine in panic disorder. Archives of General Psychiatry, 42, 233–243.

    Article  PubMed  CAS  Google Scholar 

  • Chou, D. T., Khan, S., Forde, J., and Hirsh, K. R. (1985). Caffeine tolerance: Behavioral, electrophysiological and neurochemical evidence. Life Sciences, 36, 2347–2358.

    Article  PubMed  CAS  Google Scholar 

  • Coffey, C. E., Figiel, S., and Weiner, R. D. (1990). Caffeine augmentation of ECT. American Journal of Psychiatry, 147, 579–85.

    PubMed  CAS  Google Scholar 

  • Coffin, V. L., and Carney, J. M. (1983). Behavioral pharmacology of adenosine analogs. In J. W. Daly, Y. Kuroda, J. W. Phillis, H. Shimizu, and M. Ui (Eds.), Physiology and pharmacology of adenosine derivatives (pp. 267–274 ). New York: Raven.

    Google Scholar 

  • Cole, J. O., Pope, H. G., Jr., Labrie, R., and lonescu-Pioggia, M. (1978). Assessing the subjective effects of stimulants in casual users. A methodology and preliminary results. Clinical Pharmacology and Therapeutics, 24, 243–252.

    PubMed  CAS  Google Scholar 

  • Collins, R. J., Weeks, J. R., Cooper, M. M., Good, P. I., and Russell, R. R. (1984). Prediction of abuse liability of drugs using IV self-administration by rats. Psycho-pharmacology (Berlin), 82, 6–13.

    Article  CAS  Google Scholar 

  • Colton, T., Gosselin, R. E., and Smith, R. P. (1968). The tolerance of coffee drinkers to caffeine. Clinical Pharmacology and Therapeutics, 9, 31–39.

    PubMed  CAS  Google Scholar 

  • Comer, S. D., Haney, M., Foltin, R. W., and Fischman, M. W. (1997). Effects of caffeine withdrawal on humans living in a residential laboratory. Experimental and Clinical Psvchopharn:acology 5, 399–403.

    Article  CAS  Google Scholar 

  • Denaro, C. P, Brown, C. R., Jacob, P., III, and Benowitz, N. L. (1991). Effects of caffeine with repeated dosing. European Journal of Clinical Pharmacology 40, 273–278.

    Article  PubMed  CAS  Google Scholar 

  • Deneau, G., Yanagita, T., and Seevers, M. H. (1969). Self-administration of psychoactive substances by the monkey. Psychopharmacologia, 16, 30–48.

    Article  PubMed  CAS  Google Scholar 

  • Dreisbach, R. H., and Pfeiffer, C. (1943). Caffeine-withdrawal headache. Journal of Laboratory and Clinical Medicine, 28, 1212–1219.

    CAS  Google Scholar 

  • Dworkin, S. I., Vrana, S. L., Broadbent, J., and Robinson, J. H. (1993). Comparing the effects of nicotine, caffeine, methylphenidate and cocaine. Medicinal Chemistry Research, 2, 593–602.

    CAS  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. Journal of Pharmacology and Experimental Therapeutics, 33, 167–174.

    CAS  Google Scholar 

  • Evans, S. M., and Griffiths, R. R. (1991a). Dose-related caffeine discrimination in normal volunteers: Individual differences in subjective effects and self-reported cues. Behavioral Pharmacology, 2, 345–356.

    Google Scholar 

  • Evans, S. M., and Griffiths, R. R. (1991b). Low-dose caffeine physical dependence in normal subjects: Dose-related effects. In L. S. Harris (Ed.), Problems of drug dependence, /990 (NIDA Research Monograph No. 105, pp. 446–447 ). Washington, DC: U.S. Government Printing Office.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Evans, S. M., and Griffiths, R. R. Caffeine withdrawal: A parametric analysis of caffeine dosing conditions. Manuscript submitted for publication.

    Google Scholar 

  • Evans, S. M., and Johanson, C. E. (1987). Amphetamine-like effects of anorectics and related compounds in pigeons. Journal of Pharmacology and Experimental Therapeutics, 241, 817–825.

    PubMed  CAS  Google Scholar 

  • Evans, S. M., Critchfield, T. S., and Griffiths, R. R. (1994). Caffeine reinforcement demonstrated in a majority of moderate caffeine users. Behavioral Pharmacology, 5, 231–238.

    Article  CAS  Google Scholar 

  • Fennelly, M., Galletly, D. C., and Purdie, G. I. (1991). Is caffeine withdrawal the mechanism for postoperative headache? Anesthesia and Analgesia, 72, 449–53.

    Article  PubMed  CAS  Google Scholar 

  • File, S. E., Bond, A. J., and Lister, R. G. (1982). Interaction between effects of caffeine and lorazepam in performance tests and self-ratings. Journal of Clinical Psychopharmacologv, 2, 102–106.

    CAS  Google Scholar 

  • File, S. E., Baldwin, H. A., Johnston, A. L., and Wilks, L. J. (1988). Behavioral effects of acute and chronic administration of caffeine in the rat. Pharmacology, Biochemistry and Behavior, 30, 809–815.

    Article  CAS  Google Scholar 

  • Finn, I. B., and Holtzman, S. G. (1986). Tolerance to caffeine-induced stimulation of locomotor activity in rats. Journal of Pharmacology and Experimental Therapeutics, 238, 542–546.

    PubMed  CAS  Google Scholar 

  • Finn, I. B., and Holtzman, S. G. (1987). Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity. Psychopharmacologv, 93, 428–434.

    CAS  Google Scholar 

  • Finn, I. B., and Holtzman, S. G. (1988). Tolerance and cross-tolerance to theophylline-induced stimulation of locomotor activity in rats. Life Sciences, 42, 2475–2482.

    Article  PubMed  CAS  Google Scholar 

  • Forbes, J. A., Beaver, W. T., Jones, K. F., Kehm, C. J., Smith, W. K., Gongloff, C. M., Zeleznock, J. R., and Smith, J. W. (1991). Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain. Clinical Pharmacology and Therapeutics, 49, 674–684.

    Article  PubMed  CAS  Google Scholar 

  • Froberg, J., Karlsson, C. G., Levi, L., Linde, L., and Seeman, K. (1969). Test performance and subjective feelings as modified by caffeine-containing and caffeine-free coffee. In F. Heim, H. P. T. Ammon, and F. K. Schattauer (Eds.), Koffein and andere rnethylranthine (pp. 15–20 ). Stuttgart, Germany: Springer.

    Google Scholar 

  • Galletly, D. C., Fennelly, M., and Whitman, J. G. (1989). Does caffeine withdrawal contribute to postanaesthetic morbidity? Lancet, 1, 1335.

    Article  PubMed  CAS  Google Scholar 

  • Garrett, B. E., and Griffiths, R. R. (in press). Physical dependence increases the relative reinforcing effects of caffeine versus placebo. Psychopharmacologv.

    Google Scholar 

  • Gauvin, D. V, Harland, R. D., Michaelis, R. C., and Holloway, F. A. (1989). Caffeine-phenylethylamine combinations mimic the cocaine discriminative cue. Life Sciences, 44, 67–73.

    Article  PubMed  CAS  Google Scholar 

  • Gauvin, D. V, Peirce, J. M., and Holloway, E A. (1994). Perceptual masking of the chlordiazepoxide discriminative cue by both caffeine and buspirone. Pharmacology, Biochemistry and Behavior 47, 153–159.

    Article  CAS  Google Scholar 

  • Gilbert, R. M. (1976). Caffeine as a drug of abuse. In R. J. Gibbins, Y. Israel, H. Kalant, R. E. Popham, W. I. Schmidt, and R. G. Smart (Eds.), Research advances in alcohol and drug problems (pp. 49–176 ). New York: Wiley.

    Google Scholar 

  • Gilbert, R. M. (1984). Caffeine consumption. In G. A. Spiller (Ed.), The methylxanthine beverages and foods: Chemistry, consumption, and health effects (pp. 185–213 ). New York: Liss.

    Google Scholar 

  • Goldstein, A. (1964). Wakefulness caused by caffeine. Naunvn Schmiedebergs Archiv fur Experimentelle Pathologie and Pharmakologie, 248, 269–278.

    CAS  Google Scholar 

  • Goldstein, A., and Kaizer, S. (1969). Psychotropic effects of caffeine in man: 3. A questionnaire survey of coffee drinking and its effects in a group of housewives. Clinical Pharmacology and Therapeutics, 10, 477–488.

    PubMed  CAS  Google Scholar 

  • Goldstein, A., Kaizer, S., and Warren, R. (1965). Psychotropic effects of caffeine in man: Il. Alertness, psychomotor coordination, and mood. Journal of Pharmacology and Experimental Therapeutics, 150, 146–151.

    PubMed  CAS  Google Scholar 

  • Goldstein, A., Warren, R., and Kaizer, S. (1965). Psychotropic effects of caffeine in man. I. Individual differences in sensitivity to caffeine-induced wakefulness. Journal of Pharmacology and Experimental Therapeutics, 149, 156–159.

    PubMed  CAS  Google Scholar 

  • Goldstein, A., Kaizer, S., and Whitby, O. (1969). Psychotropic effects of caffeine in man: IV. Quantitative and qualitative differences associated with habituation to coffee. Clinical Pharmacology and Therapeutics, 70, 489–497.

    Google Scholar 

  • Goldstein, I. B., Shapiro, D., Hui, K. K., and Yu, J. L. (1990). Blood pressure response to the “second cup of coffee” Psychosomatic Medicine, 52, 337–345.

    PubMed  CAS  Google Scholar 

  • Graham, D. M. (1978). Caffeine-Its identity, dietary sources, intake and biological effects. Nutritional Reviews, 36, 97–102.

    CAS  Google Scholar 

  • Greden, J. F. (1981). Caffeinism and caffeine withdrawal. In J. H. Lowinson and P. Reiz (Eds.), Substance abuse: Clinical problems and perspectives (pp. 274–286 ). Baltimore: Williams and Wilkins.

    Google Scholar 

  • Greden, J. F., Fontaine, P, Lubetsky, M., and Chamberlin, K. (1978). Anxiety and depression associated with caffeinism among psychiatric inpatients. American Journal of Psychiatry, 135, 963–966.

    PubMed  CAS  Google Scholar 

  • Greden, J. F., Victor, B. S., Fontaine, P., and Lubetsky, M. (1980). Caffeine-withdrawal headache: A clinical profile. Psychosomatics, 27, 411–418.

    Google Scholar 

  • Griffiths, R. R., and Mumford, G. K. (1995). Caffeine-A drug of abuse? In E E. Bloom and D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 1699–1713 ). New York: Raven.

    Google Scholar 

  • Griffiths, R. R., and Mumford, G. K. (1996). Caffeine reinforcement, discrimination, tolerance and physical dependence in laboratory animals and humans. In C. R. Schuster and M. J. Kuhar (Eds.), Handbook of experimental pharmacology (Vol. 118, pp. 315–341 ). Heidelberg, Germany: Springer-Verlag.

    Google Scholar 

  • Griffiths, R. R., and Woodson, P. P. (1988a). Caffeine physical dependence: A review of human and laboratory animal studies. Psychopharmacology, 94, 437–451.

    Article  PubMed  CAS  Google Scholar 

  • Griffiths, R. R., and Woodson, P. P. (1988b). Reinforcing effects of caffeine in humans. Journal of Pharmacology and Experimental Therapeutics, 246, 21–29.

    PubMed  CAS  Google Scholar 

  • Griffiths, R. R., and Woodson, P. P. (1988c). Reinforcing properties of caffeine: Studies in humans and laboratory animals. Pharmacology, Biochemistry and Behavior, 29, 419–427.

    Article  CAS  Google Scholar 

  • Griffiths, R. R., Brady, J. V, and Bradford, L. D. (1979). Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons. Psycho-pharmacology, 65, 125–136.

    Article  CAS  Google Scholar 

  • Griffiths, R. R., Bigelow, G. E., and Henningfield, J. E. (1980). Similarities in animal and human drug-taking behavior. In N. K. Mello (Ed.), Advances in substance abuse (Vol. 1, pp. 1–90 ). Greenwich, CT: JAI.

    Google Scholar 

  • Griffiths, R. R., Bigelow, G. E., and Liebson, I. A. (1986). Human coffee drinking: Reinforcing and physical dependence producing effects of caffeine. Journal of Pharmacology and Experimental Therapeutics, 239, 416–425.

    PubMed  CAS  Google Scholar 

  • Griffiths, R. R., Bigelow, G. E., Liebson, I. A., O’Keefe, M., O’Leary, D., and Russ, N. (1986). Human coffee drinking: Manipulation of concentration and caffeine dose. Journal of the Experimental Analysis of Behavior, 45, 133–148.

    Article  PubMed  CAS  Google Scholar 

  • Griffiths, R. R., Bigelow, G. E., and Liebson, I. A. (1989). Reinforcing effects of caffeine in coffee and capsules. Journal of the Experimental Analysis of Behavior. 52, 127–140.

    Article  PubMed  CAS  Google Scholar 

  • Griffiths, R. R., Evans, S. M., Heishman, S. J., Preston, K. L., Sannerud, C. A., Wolf, B., and Woodson, P. P. (1990a). Low-dose caffeine discrimination in humans. Journal of Pharmacology and Experimental Therapeutics, 252, 970–978.

    PubMed  CAS  Google Scholar 

  • Griffiths, R. R., Evans, S. M., Heishman, S. J., Preston, K. L., Sannerud, C. A., Wolf, B., and Woodson, P. P. (1990b). Low-dose caffeine physical dependence in humans. Journal of Pharmacology and Experimental Therapeutics, 255, 1123–1132.

    PubMed  CAS  Google Scholar 

  • Gurling, H. M., Grant, S., and Dangl, J. (1985). The genetic and cultural transmission of alcohol use, alcoholism, cigarette smoking and coffee drinking: A review and an example using a log linear cultural transmission model. British Journal of Addiction, 80, 269–279.

    Article  PubMed  CAS  Google Scholar 

  • Haertzen, C. A. (1974). An overview of Addiction Research Center Inventory Scales (ARC!): An appendix and Manual of Scales (U.S. Department of Health and Human Services Publication No. (ADM) 74–92 ). Rockville, MD.

    Google Scholar 

  • Haigh, R. A., Harper, G. D., Fotherby, M., Hurd, J., Macdonald, I. A., and Potter, J. F. (1993). Duration of caffeine abstention influences the acute blood pressure responses to caffeine in elderly normotensives. European Journal of Clinical Pharmacolog; 44, 549–553.

    Article  CAS  Google Scholar 

  • Hale, K. L, Hughes, J. R., Oliveto, A. H., and Higgins, S. T. (1995). Caffeine self-administration and subjective effects in adolescents. Experimental and Clinical Psychopharmacology, 3, 364–370.

    Article  CAS  Google Scholar 

  • Harland, R. D., Gauvin, D. V, Michaelis, R. C., Carney, J. M., Seale, T. W, and Holloway, F. A. (1989). Behavioral interaction between cocaine and caffeine: A drug discrimination analysis in rats. Pharmacology, Biochemistry and Behavior, 32, 1017–1023.

    Article  CAS  Google Scholar 

  • Hasenfratz, M., and Bättig, K. (1994). Acute dose-effect relationships of caffeine and mental performance, EEG, cardiovascular and subjective parameters. Psychopharmacology, 114, 281–287.

    Article  PubMed  CAS  Google Scholar 

  • Heishman, S. J., and Henningfield, J. E. (1992). Stimulus functions of caffeine in humans: Relation to dependence potential. Neuroscience and Biobehavioral Reviews, 16, 273–287.

    Article  PubMed  CAS  Google Scholar 

  • Heishman, S. J., Taylor, R. C., Goodman, M. L., Evans, S. M., and Henningfield, J. E. (1993). Discriminative stimulus effects of d-amphetamine, caffeine, and mazindol in humans. Pharmacology, Biochemistry and Behavior, 46, 502–503.

    Article  Google Scholar 

  • Heppner, C. C., Kemble, E. D., and Cox, W. M. (1986). Effects of food deprivation on caffeine consumption in male and female rats. Pharmacology, Biochemistry and Behavior; 24, 1555–1559.

    Article  CAS  Google Scholar 

  • Heseltine, D., Dakkak, M., Woodhouse, K., Macdonald, I. A., and Potter, J. F. (1991). The effect of caffeine on postprandial hypotension in the elderly. Journal of the American Geriatric Society 39, 160–164.

    CAS  Google Scholar 

  • Hoffmeister, E, and Wuttke, W. (1973). Negative reinforcing properties of morphine-antagonists in naive rhesus monkeys. Psychopharmacologia, 33, 247–258.

    Article  PubMed  CAS  Google Scholar 

  • Holloway, E. A., Michaelis, R. C., and Huerta, P. L. (1985). Caffeine-phenylethylamine combinations mimic the amphetamine discriminative cue. Life Sciences, 36, 723–730.

    Article  PubMed  CAS  Google Scholar 

  • Holloway, E A., Modrow, H. E., and Michaelis, R. C. (1985). Methylxanthine discrimination in the rat: Possible benzodiazepine and adenosine mechanisms. Pharmacology, Biochemistry and Behavior, 22, 815–824.

    Article  CAS  Google Scholar 

  • Holtzman, S. G. (1983). Complete, reversible, drug-specific tolerance to stimulation of locomotor activity by caffeine. Life Sciences, 33, 779–787.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman, S. G. (1986). Discriminative stimulus properties of caffeine in the rat: Noradrenergic mediation. Journal of Pharmacology and Experimental Therapeutics, 239, 706–714.

    PubMed  CAS  Google Scholar 

  • Holtzman, S. G. (1987). Discriminative stimulus effects of caffeine: Tolerance and cross-tolerance with methylphenidate. Life Sciences, 40, 381–389.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman, S. G. (1990). Caffeine as a model drug of abuse. Trends in Pharmacologic Science, 11, 355–356.

    Article  CAS  Google Scholar 

  • Holtzman, S. G. (1991). CGS 15943, a nonxanthine adenosine receptor antagonist: Effects on locomotor activity of nontolerant and caffeine-tolerant rats. Life Sciences, 49, 1563–1570.

    Article  PubMed  CAS  Google Scholar 

  • Holtzman, S. G., and Finn, 1. B. (1988). Tolerance to behavioral effects of caffeine in rats. Pharmacology, Biochemistry and Behavior, 29, 411–418.

    Article  CAS  Google Scholar 

  • Holtzman, S. G., and Villarreal, J. (1973). Operant behavior in the morphine-dependent rhesus monkey. Journal of Pharmacology and Experimental Therapeutics, 184, 528–541.

    PubMed  CAS  Google Scholar 

  • Howell, L. L., and Landrum, A. M. (1997). Effects of chronic caffeine administration on respiration and schedule-controlled behavior in rhesus monkeys. Journal of Pharmacology and Experimental Thempeutics, 283, 190–199.

    CAS  Google Scholar 

  • Hughes, J. R. (1992). Clinical importance of caffeine withdrawal. New England Journal of Medicine, 327, 1160–1161.

    Article  PubMed  CAS  Google Scholar 

  • Hughes, J. R., Higgins, S. T., Bickel, W. K., Hunt, W. K., Fenwick, J. W., Gulliver, S. B., and Mireault, G. C. (1991). Caffeine self-administration, withdrawal, and adverse effects among coffee drinkers. Archives of General Psychiatry, 48, 611–617.

    Article  PubMed  CAS  Google Scholar 

  • Hughes, J. R., Hunt, W. K., Higgins, S. T., Bickel, W. K., Fenwick, J. W, and Pepper, S. L. (1992). Effect of dose on the ability of caffeine to serve as a reinforcer in humans. Behavioural Pharmacology, 3, 211–218.

    Article  PubMed  CAS  Google Scholar 

  • Hughes, J. R., Oliveto, A. H., Bickel, W. K., Higgins, S. T., and Valliere, W. (1992). Caffeine self-administration and withdrawal in soda drinkers. Journal of Addictive Diseases, 4, 178.

    Google Scholar 

  • Hughes, J. R., Oliveto, A. H., Hetzer, J. E., Higgins, S. T., and Bickel, W. K. (1992). Should caffeine abuse, dependence or withdrawal be added to DSM-IV or ICD-I0? American Journal of Psychiatry, 149, 33–40.

    PubMed  CAS  Google Scholar 

  • Hughes, J. R., Oliveto, A. H., Bickel, W. K., Higgins, S. T., and Badger, G. J. (1993). Caffeine self-administration and withdrawal: Incidence, individual differences and interrelationships. Drug and Alcohol Dependence, 32, 239–246.

    Article  PubMed  CAS  Google Scholar 

  • Hughes, J. R., Oliveto, A. H., Hetzer, J. E., Bickel, W. K., and Higgins, S. T. (1993). Indications of caffeine dependence in a population-based sample. In L. S. Harris (Ed.), Problems of drug dependence, /992 (p. 194 ). Washington, DC: U.S. Government Printing Office.

    Google Scholar 

  • Hughes, J. R., Oliveto, A. H., Bickel, W. K., Higgins, S. T., and Badger, G. J. (1995). The ability of low doses of caffeine to serve as reinforcers in humans: A replication. Experimental and Clinical Psychopharmacology, 3, 358–363.

    Article  CAS  Google Scholar 

  • Johanson, C. E. (1978). Drugs as reinforcers. In D. E. Blackman and D. J. Sanger (Eds.), Contemporary research in behavioral pharmacology (pp. 325–390 ). New York: Plenum.

    Chapter  Google Scholar 

  • Jones, C. N., Howard, J. L., and Bennett, S. T. (1980). Stimulus properties of antidepressants in the rat. Psychopharmacology (Berlin), 67, 111–118.

    Google Scholar 

  • Kamien, J. B., Bickel, W. K., Hughes, J. R., Higgins, S. T., and Smith, B. J. (1993). Drug discrimination by humans compared to nonhumans: Current status and future directions. Psychopharmac000gv, 111, 259–270.

    Article  CAS  Google Scholar 

  • Kaplan, G. B., Greenblatt, D. J., Kent, M. A., and CotreauBibbo, M. M. (1993). Caffeine treatment and withdrawal in mice: Relationships between dosage, concentrations, locomotor activity and A, adenosine receptor binding. Journal of Pharmacology and Experimental Therapeutics, 266, 1563–1572.

    PubMed  CAS  Google Scholar 

  • Katz, J. L., and Goldberg, S. R. (1987). Psychomotor stimulant effects of caffeine alone and in combination with an adenosine analog in the squirrel monkey. Journal of Pharmacology and Experimental Therapeutics, 242, 179–187.

    PubMed  CAS  Google Scholar 

  • Kozlowski, L. T. (1976). Effect of caffeine on coffee drinking. Nature, 264, 354–355.

    Article  PubMed  CAS  Google Scholar 

  • Kuhn, D. M., Appel, J. B., and Greenberg, I. (1974). An analysis of some discriminative properties of d-amphetamine. Psychopharmacologia, 39, 57–66.

    Article  PubMed  CAS  Google Scholar 

  • Lane, J. D,. and Manus, D. C. (1989). Caffeine may potentiate adrenocortical stress responses in hypertension-prone men. Hypertension, 14, 170–176.

    Google Scholar 

  • Lane, J. D., and Williams, R. B. (1987). Cardiovascular effects of caffeine and stress in regular coffee drinkers. Psychophysiology, 24, 157–64.

    Article  PubMed  CAS  Google Scholar 

  • Laska, E. M., Sunshine, A., Mueller, E, Elvers, W. B., Siegel, C., and Rubin, A. (1984). Caffeine as an analgesic adjuvant. Journal of the American Medical Association, 251, 1711–1718.

    Article  PubMed  CAS  Google Scholar 

  • Lau, C. E., and Falk, J. L. (1994). Tolerance to oral and IP caffeine: Locomotor activity and pharmacokinetics. Pharmacology, Biochemistry and Behavior, 48, 337344.

    Google Scholar 

  • Lau, C. E., and Falk, J. L. (1995). Dose-dependent surmountability of locomotor activity in caffeine tolerance. Pharmacology, Biochemistry and Behavior, 52, 139–143.

    Article  CAS  Google Scholar 

  • Leathwood, P. D., and Pollet, P. (1983). Diet-induced mood changes in normal populations. Journal of Psychiatric Research, 17, 147–154.

    Article  CAS  Google Scholar 

  • Lee, M. A., Cameron, O. G., and Greden, J. E (1985). Anxiety and caffeine consumption in people with anxiety disorders. Psychiatry Research, 15, 211–217.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, H. R., Wurtman, R. J., Emde, G. G., and Coviella, I. L. (1987). The effects of caffeine and aspirin on mood and performance. Journal of Clinical Psychopharmacology, 7, 315–320.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, H. R., Wurtman, R. J., Emde, G. G.. Roberts, C., and Coviella, I. L. (1987). The effects of low doses of caffeine on human performance and mood. Psychopharmacology, 92, 308–312.

    CAS  Google Scholar 

  • Ligori, A., and Hughes, J. R. (1997). Caffeine self-administration in humans: 2. A within-subjects comparison of coffee and cola vehicles. Experimental and Clinical Psychopharmacology, 5, 195–303.

    Article  Google Scholar 

  • Ligori, A., Hughes, J. R., and Oliveto, A. H. (1997). Caffeine self-administration in humans: 1. Efficacy of cola vehicle. Experimental and Clinical Psychopharmacology, 5, 286–294.

    Article  Google Scholar 

  • Loke, W. H. (1988). Effects of caffeine on mood and memory. Physiology and Behavior; 44, 367–372.

    Article  PubMed  CAS  Google Scholar 

  • Mariathasan, E. A., and Stolerman, I. P. (1992). Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures. Psychopharmacology (Berlin), 109, 99–106.

    Article  CAS  Google Scholar 

  • Meisch; R. A. (1977). Ethanol self-administration: Infrahuman studies. In T. Thompson and P. B. Dews (Eds.), Advances in behavioral pharmacology (Vol. I, pp. 35–84 ). New York: Academic Press.

    Google Scholar 

  • Mitchell, S. H., de Wit, H., and Zacny, J. P. (1995). Caffeine withdrawal symptoms and self-administration following caffeine deprivation. Pharmacology, Biochemistry and Behavior 51, 941–945.

    Article  CAS  Google Scholar 

  • Modrow, H. E., and Holloway, F. A. (1985). Drug discrimination and cross generalization between two methyl-xanthines. Pharmacology, Biochemistry and Behavior, 23, 425–429.

    Article  CAS  Google Scholar 

  • Modrow, H. E., Holloway, F. A., and Carney, M. (1981). Caffeine discrimination in the rat. Pharmacology, Biochemistry and Behavior, 14, 683–688.

    Article  CAS  Google Scholar 

  • Modrow, H. E., Holloway, F. A., Christensen, H. D., and Carney, M. (1981). Relationship between caffeine discrimination and caffeine plasma levels. Pharmacology, Biochemistry and Behavior, 15, 323–325.

    Article  CAS  Google Scholar 

  • Mumford, G. K., and Holtzman, S. G. (1991). Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. Journal of Pharmacology and Experimental Therapeutics, 258, 857–865.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Mumford, G. K., Evans, S. M., Kaminski, B. J., Preston, K. L., Sannerud, C. A., Silverman, K., and Griffiths, R. R. (1994). Discriminative stimulus and subjective effects of theobromine and caffeine in humans. Psychopharmacology, 115, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Nehlig, A., Daval J., and Debry G. (1992). Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Research Reviews, 17, 139–170.

    Article  PubMed  CAS  Google Scholar 

  • Nikodijevic, O., Jacobson, K. A., and Daly, J. W. (1993). Locomotor activity in mice during chronic treatment with caffeine and withdrawal. Pharmacology, Biochemistry and Behavior; 44, 199–216.

    Article  CAS  Google Scholar 

  • Oliveto, A. H., Hughes, J. R., Pepper, S. L., Bickel, W. K., and Higgins, S. T. (1991). Low doses of caffeine can serve as reinforcers in humans. In L. S. Harris (Ed.), Problems of drug dependence, 1990 (N I DA Research Monograph No. 105, p. 442 ). Washington, DC: U.S. Government Printing Office.

    Google Scholar 

  • Oliveto, A. H., Bickel, W. K., Hughes, J. R., Shea, P. J., Higgins, S. T., and Fenwick, J. W. (1992). Caffeine drug discrimination in humans: Acquisition, specificity and correlation with self-reports. Journal of Pharmacology and Experimental Therapeutics, 261, 885–894.

    PubMed  CAS  Google Scholar 

  • Oliveto, A. H., Hughes, J. R., Higgins, S. T., Bickel, W. K., Pepper, S. L., and Shea, P. J. (1992). Forced-choice versus free-choice procedures: Caffeine self-administration in humans. Psychopharmacology, 109, 85–91.

    Article  PubMed  CAS  Google Scholar 

  • Oliveto, A. H., Bickel, W. K., Hughes, J. R., Terry, S. Y., Higgins, S. T., and Badger, G. J. (1993). Pharmacological specificity of the caffeine discriminative stimulus in humans: Effects of theophylline, methylphenidate and buspirone. Behavioural Pharmacology, 4, 237–246.

    Article  PubMed  CAS  Google Scholar 

  • Overton, D. A. (1973). State dependent learning produced by addicting drugs. Psychopharmacology Bulletin, 9, 29–31.

    Google Scholar 

  • Overton, D. A., and Batta, S. K. (1977). Relationship between abuse liability of drugs and their degree of discriminability in the rat. In T. Thompson and K. Unna (Eds.), Predicting dependence liability of stimulant and depressant drugs (pp. 125–135 ). Baltimore: University Park Press.

    Google Scholar 

  • Pedersen, N. (1981). Twin similarity for usage of common drugs. Progress in Clinical and Biological Research, 69, 53–59.

    PubMed  Google Scholar 

  • Podboy, J. W., and Malloy, W. A. (1977). Caffeine reduction and behavior change in the severely retarded. Mental Retardation, 15, 40.

    PubMed  CAS  Google Scholar 

  • Richardson, N. J., and Rogers, P. J. (1993). Caffeine, caffeine withdrawal, and preference for caffeine-containing beverages. Appetite, 21, 201.

    Article  Google Scholar 

  • Richardson, N. J., Rogers, P. J., Elliman, N. A., and O’Dell, R. J. (1995). Mood and performance effects of caffeine in relation to acute and chronic caffeine deprivation. Pharmacology, Biochemistry and Behavior, 52, 313–320.

    Article  CAS  Google Scholar 

  • Rizzo, A. A., Stamps, L. E., and Fehr, L. A. (1988). Effects of caffeine withdrawal on motor performance and heart rate changes. International Journal of Psychophysiology, 6, 9–14.

    Article  PubMed  CAS  Google Scholar 

  • Robertson, D., Wade, D., Workman, R., and Woosley, R. L. (1981). Tolerance to the humoral and hemodynamic effects of caffeine in man. Journal of Clinical Investigation, 67, 1111–1117.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, J. B., Young, A. M., Beuthin, F. C., and LouisFerdinant, R. T. (1986). Discriminative stimulus properties of amphetamine and other stimulants in lead-exposed and normal rats. Pharmacology, Biochemistry and Behavior, 24. 211–215.

    Article  CAS  Google Scholar 

  • Rush, C. R., Sullivan, J. T., and Griffiths, R. R. (1995). Intravenous caffeine in stimulant drug abusers: Subjective reports and physiological effects. Journal of Pharmacology and Experimental Therapeutics, 273, 351–358.

    PubMed  CAS  Google Scholar 

  • Sawynok, J. (1995). Pharmacological rationale for the clinical use of caffeine. Drugs, 49, 37–50.

    Article  PubMed  CAS  Google Scholar 

  • Sawynok, J., and Yaksh, T. L. (1993). Caffeine as an analgesic adjuvant: A review of pharmacology and mechanisms of action. Pharmacological Reviews, 45, 43–85.

    PubMed  CAS  Google Scholar 

  • Schechter, M. D. (1977). Caffeine potentiation of amphetamine: Implications for hyperkinesis therapy. Pharmacology, Biochemistry and Behavior, 6, 359–361.

    Article  CAS  Google Scholar 

  • Schechter, M. D. (1989). Potentiation of cathinone by caffeine and nikethamide. Pharmacology, Biochemistry and Behavior, 33, 299–301.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Schulte-Daxboek, G., and Opitz, K. (1981). Increased caffeine consumption following chronic nicotine treatment in rats. IRCS Journal of Medical Science, 9, 1062.

    CAS  Google Scholar 

  • Schuster, C. R., and Johanson, C. E. (1988). Relationship between the discriminative stimulus properties and subjective effects of drugs. Psychopharmacology Series, 4, 161–175.

    PubMed  CAS  Google Scholar 

  • Schuster, C. R., Woods, J. H., and Seevers, M. H. (1969). Self-administration of central stimulants by the monkey. In E Sjoqvist and M. Tottie (Eds.), Abuse of central stimulants (pp. 339–347 ). New York: Raven.

    Google Scholar 

  • Schuster, C. R., Fischman, M. W, and Johanson, C. E. (1981). Internal stimulus control and subjective effects of drugs. In C. E. Johanson and T. Thompson (Eds.), Behavioral pharmacology of human drug dependence (NIDA Research Monograph No. 37, pp. 16–129 ). Washington, DC: U.S. Government Printing Office.

    Google Scholar 

  • Sechzer, P. H. (1979). Post spinal anesthesia headache treated with caffeine: Part II. Intracranial vascular distension, a key factor. Current Therapeutic Research, 26, 440–448.

    Google Scholar 

  • Shi, J., Benowitz, N. L., Denaro, C. P., and Sheiner, L. B. (1993). Pharmacokinetics and drug disposition. Pharmacokinetic-pharmacodynamic modeling of caffeine: Tolerance to pressor effects. Clinical Pharmacology and Therapeutics, 53, 6–14.

    Article  PubMed  CAS  Google Scholar 

  • Shorofsky, M. A., and Lamm, R. N. (1977). Caffeine-withdrawal headache and fasting. New York State Journal of Medicine, 77, 217–218.

    PubMed  CAS  Google Scholar 

  • Silverman, K., and Griffiths, R. R. (1992). Low-dose caffeine discrimination and self-reported mood effects in normal volunteers. Journal of the Experimental Analysis of Behavior, 57, 91–107.

    Article  PubMed  CAS  Google Scholar 

  • Silverman, K., Evans, S. M., Strain, E. C., and Griffiths, R. R. (1992). Withdrawal syndrome after the double-blind cessation of caffeine consumption. New England Journal of Medicine, 327, 1109–1114.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Silverman, K., Mumford, G. K., and Griffiths, R. R. (1994b). A procedure for studying the within-session onset of human drug discrimination. Journal of the Experimental Analysis of Behavior. 61. 181–189.

    Article  PubMed  CAS  Google Scholar 

  • Spencer, D. G., and Lal, H. (1983). Discriminative stimulus properties of L-phenylisopropyladenosine: Blockade by caffeine and generalization to 2-chloradenosine. Life Science, 32, 2329–2333.

    Article  CAS  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.

    Article  PubMed  CAS  Google Scholar 

  • Strain, E. C., and Griffiths, R. R. (1997). Caffeine. In A. Tasman, J. Kay, and J. A. Lieberman (Eds.), Psychiatry (Vol. 1, pp. 779–794 ). Philadelphia: Saunders.

    Google Scholar 

  • Strain, E. C., Mumford, G. K., Silverman, K., and Griffiths, R. R. (1994). Caffeine dependence syndrome: Evidence from case histories and experimental evaluations. Journal of the American Medical Association, 272, 1043–1048.

    Article  PubMed  CAS  Google Scholar 

  • Uhde, T. W (1990). Caffeine provocation of panic: A focus on biological mechanisms. In J. C. Ballenger (Ed.), Neurobiology of panic disorder (pp. 219–242 ). New York: Liss.

    Google Scholar 

  • Uhde, T. W, Boulenger, J. E, Jimerson, D. C., and Post, R. M. (1984). Caffeine: Relationship to human anxiety, plasma MHPG and cortisol. Psychopharmacology Bulletin, 20, 426–430.

    PubMed  CAS  Google Scholar 

  • Victor, B. S., Lubetsky, M., and Greden, J. F. (1981). Somatic manifestations of caffeinism. Journal of Clinical Psychiatry, 42, 185–188.

    PubMed  CAS  Google Scholar 

  • Vitiello, M. V, and Woods, S. C. (1975). Caffeine: Preferential consumption by rats. Pharmacology, Biochemistry and Behavior 3, 147–149.

    Article  CAS  Google Scholar 

  • Vitiello, M. V, and Woods, S. C. (1977). Evidence for withdrawal from caffeine by rats. Pharmacology, Biochemistry and Behavior, 6, 553–555.

    Article  CAS  Google Scholar 

  • Wayner, M. L., Jolicoeur, E B., Rondeu, D. B., and Barone, F. C. (1976). Effects of acute and chronic administration of caffeine on schedule dependent and schedule induced behavior. Pharmacology, Biochemistry and Behavior, 5, 343–348.

    Article  CAS  Google Scholar 

  • Weber, J. G., Ereth, M. H., and Danielson, D. R. (1993). Perioperative ingestion of caffeine and postoperative headache. Mayo Clinic Proceedings, 68, 843–845.

    Article  Google Scholar 

  • Weber, J. G., Klindworth, J. T., Arnold, J. J., Danielson, D. R., and Ereth, M. H. (1997). Prophylactic intravenous administration of caffeine and recovery after ambulatory surgical procedures. Mayo Clinic Proceedings, 72, 621–626.

    PubMed  CAS  Google Scholar 

  • Winsor, A. L., and Strongin, E. 1. (1933). A study of the development of tolerance for caffeinated beverages. Journal of Experimental Psychology, 16, 725–744.

    Article  Google Scholar 

  • Winter, J. C. (1981). Caffeine-induced stimulus control. Pharmacology, Biochemistry and Behavior, 15, 157–159.

    Article  CAS  Google Scholar 

  • Wood, R. W. (1990). Animal models of drug self-administration by smoking. In C. N. Chiang and R. L. Hawks (Eds.), Research findings on smoking of abused substances (NIDA Research Monograph No. 99, pp. 159–171 ). Washington, DC: U.S. Government Printing Office.

    Google Scholar 

  • Yanagita, T. (1970). Self-administration studies on various dependence-producing agents in monkeys. University of Michigan Medical Center Journal, 36, 216–224.

    Google Scholar 

  • Zwyghuizen-Doorenbose, A., Roehrs, T. A., Lipschutz, L., Timms, V. and Roth, T. (1990). Effects of caffeine on alertness. Psychopharmacology, 100, 36–39.

    Article  Google Scholar 

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  1. The New York State Psychiatric Institute, New York, New York, 10032, USA

    Suzette M. Evans

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  2. Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania, USA

    Robert T. Ammerman

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Evans, S.M. (1998). Behavioral Pharmacology of Caffeine. In: Tarter, R.E., Ammerman, R.T., Ott, P.J. (eds) Handbook of Substance Abuse. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2913-9_6

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