Skip to main content

Caffeine physical dependence: a review of human and laboratory animal studies

Abstract

Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been poorly characterized in laboratory animals and only moderately well characterized in humans. In humans, a review of 37 clinical reports and experimental studies dating back to 1833 shows that headache and fatigue are the most frequent withdrawal symptoms, with a wide variety of other signs and symptoms occurring at lower frequency (e.g. anxiety, impaired psychomotor performance, nausea/vomiting and craving). When caffeine withdrawal occurs, severity can vary from mild to extreme (i.e. incapacitating). The withdrawal syndrome has an onset at 12–24 h, peak at 20–48 h, and duration of about 1 week. The pharmacological specificity of caffeine withdrawal has been established. The proportion of heavy caffeine users who will experience withdrawal symptoms has been estimated from experimental studies to range from 25% to 100%. Withdrawal symptoms have been documented after relatively short-term exposure to high doses of caffeine (i.e. 6–15 days of ≥600 mg/day). Although animal and human studies suggest that physical dependence may potentiate the reinforcing effects of caffeine, human studies also demonstrate that a history of substantial caffeine intake is not a necessary condition for caffeine to function as a reinforcer. The similarities and differences between caffeine and classic drugs of abuse are discussed.

This is a preview of subscription content, access via your institution.

References

  • Ahlijanian MK, Takemori AE (1986) Cross-tolerance studies between caffeine and (-)-N6-(phenylisopropyl)-adenosine (PIA) in mice. Life Sci 38:577–588

    Google Scholar 

  • American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, revised. Am Psychiatr Assoc, Washington, DC

    Google Scholar 

  • Ammon HPT, Bieck PR, Mandalaz D, Verspohl EJ (1983) Adaptation of blood pressure to continuous heavy coffee drinking in young volunteers. A double-blind crossover study. Br J Clin Pharmacol 15:701–706

    Google Scholar 

  • Austin GA (1979) Perspectives on the history of psychoactive substance use. Research issues 24, DHEW publication (ADM) 79–810. US Government Printing Office, Washington, DC, pp 50–66

    Google Scholar 

  • Babington MA, Monson RA (1982) Dependence on Midol. Arch Intern Med 142:1583

    Google Scholar 

  • Barone JJ, Roberts H (1984) Human consumption of caffeine. In: Dews PB (ed) Caffeine: perspectives from recent research. Springer, Berlin Heidelberg New York Tokyo, pp 59–73

    Google Scholar 

  • Bättig K (1985) The physiological effects of coffee consumption. In: Clifford MN, Willson KC (eds) Coffee: botany, biochemistry and production of beans and beverage. The AVI Publ Comp, Westport, Connecticut, pp 394–439

    Google Scholar 

  • Bernard ME, Dennehy S, Keefauver LW (1981) Behavioral treatment of excessive coffee and tea drinking: a case study and partial replication. Behav Ther Ther 12:543–548

    Google Scholar 

  • Blanchard J, Sawers SJA (1983) Comparative pharmacokinetics of caffeine in young and elderly men. J Pharmacokinet Biopharm 11:109–126

    Google Scholar 

  • Boulenger J-P, Patel J, Post RM, Parma AM, Marangos PJ (1983) Chronic caffeine consumption increases the number of brain adenosine receptors. Life Sci 32:1135–1142

    Google Scholar 

  • Boyd EM, Dolman M, Knight LM, Sheppard EP (1965) The chronic oral toxicity of caffeine. Can J Physiol Pharmacol 43:995–1007

    Google Scholar 

  • Brady JV, Lukas SE (eds) (1984) Testing drugs for physical dependence potential and abuse liability. Natl Inst Drug Abuse Res Monogr 52. DHHS Publication No (ADM) 84–1332. US Government Printing Office, Washington, DC

    Google Scholar 

  • Bridge N (1893) Coffee-drinking as a frequent cause of disease. Trans Assoc Am Physicians 8:281–288

    Google Scholar 

  • Burns C (1977) Phensic addiction. Ulster Med J 46:100–102

    Google Scholar 

  • Carney JM (1982) Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats. Br J Pharmacol 75:451–454

    Google Scholar 

  • Carter, WR (1984) Withdrawal of caffeine from regular users: our study vs. the subjects' study. Society of Behavioral Medicine, Abstract No C93, p 40

  • Chait LD, Griffiths RR (1983) Effects of caffeine on cigarette smoking and subjective response. Clin Pharmacol Ther 34:612–622

    Google Scholar 

  • Charney DS, Galloway MP, Heninger GR (1984) The effects of caffeine on plasma MHPG, subjective anxiety, autonomic symptoms and blood pressure in healthy humans. Life Sci 35:135–144

    Google Scholar 

  • Chou DT, Khan S, Forde J, Hirsh KR (1985) Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence. Life Sci 36:2347–2358

    Google Scholar 

  • Cobbs LW (1982) Lethargy, anxiety, and impotence in a diabetic. Hosp Pract [Off] 17(8):67; 70; 73

    Google Scholar 

  • Cole J (1833) On the deleterious effects produced by drinking tea and coffee in excessive quantities. Lancet II:274–278

    Google Scholar 

  • Collins E, Turner G (1973) A suggestion for reducing the incidence of habitual analgesic consumption. Med J Aust 1:863

    Google Scholar 

  • De Busscher J, Varenne G (1966) Toxicomanie à l'Optalidon. Acta Neurol Belg 66:787–802

    Google Scholar 

  • De Freitas B, Schwartz G (1979) Effects of caffeine in chronic psychiatric patients. Am J Psychiatry 136:1337–1338

    Google Scholar 

  • Deneau G, Yanagita T, Seevers MH (1969) Self-administration of psychoactive substances by the monkey: a measure of psychological dependence. Psychopharmacologia 16:30–48

    CAS  PubMed  Google Scholar 

  • Dews PB (1982) Caffeine. Annu Rev Nutr 2:323–341

    Google Scholar 

  • Dreisbach RH, Pfeiffer C (1943) Caffeine-withdrawal headache. J Lab Clin Med 28:1212–1219

    Google Scholar 

  • Edelstein BA, Keaton-Brasted C, Burg MM (1983) The effects of caffeine withdrawal on cardiovascular and gastrointestinal responses. Health Psychol 2:343–352

    Google Scholar 

  • Ernster VL (1984) Epidemiologic studies of caffeine and human health. In: Spiller GA (ed) The methylxanthine beverages and foods: Chemistry, consumption, and health effects. Liss, New York, pp 377–400

    Google Scholar 

  • Finn IB, Holtzman SG (1986) Tolerance to caffeine-induced stimulation of locomotor activity in rats. J Pharmacol Exp Ther 238:542–546

    Google Scholar 

  • Finn IB, Holtzman SG (1987) Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity. Psychopharmacology 93:428–434

    Google Scholar 

  • Foxx RM, Rubinoff A (1979) Behavioral treatment of caffeinism: Reducing excessive coffee drinking. J Appl Behav Anal 12:335–344

    Google Scholar 

  • Franklin JC, Schiele BC, Brozek J, Keys A (1948) Observations on human behavior in experimental semistarvation and rehabilitation. J Clin Psychol 4:28–45

    Google Scholar 

  • Furlong FW (1975) Possible psychiatric significance of excessive coffee consumption. Can Psychiatr Assoc J 20:577–583

    Google Scholar 

  • Gardos G (1977) Dyskinesia after discontinuation of compound analgesic containing oxycodone. Lancet I:759–760

    Google Scholar 

  • Gault MH, Rudwal TC, Redmond NI (1968) Analgesic habits of 500 veterans: Incidence and complications of abuse. Can Med Assoc J 98:619–626

    Google Scholar 

  • Gibson CJ (1981) Caffeine withdrawal elevates urinary MHPG excretion. N Engl J Med 304:363

    Google Scholar 

  • Gilbert RM (1976a) Caffeine as a drug of abuse. In: Gibbins RJ, Israel Y, Kalant H, Popham RE, Schmidt W, Smart RG (eds) Research advances in alcohol and drug problems, vol 3. Wiley, New York, pp 49–176

    Google Scholar 

  • Gilbert RM (1976b) Tea toxicity. JAMA 236:1452

    Google Scholar 

  • Gilbert RM (1984) Caffeine consumption. In: Spiller GA (ed) The methylxanthine beverages and foods: Chemistry, consumption, and health effects. Liss, New York, pp 185–213

    Google Scholar 

  • Gilles de la Tourette, Gasne (1895) Sur l'intoxication chronique par le café. Bull Mem Soc Med Hop Paris 12:558–566

    Google Scholar 

  • Goldberg MR, Curatolo PW, Tung C-S, Robertson D (1982) Caffeine down-regulates β-adrenoreceptors in rat forebrain. Neurosci Lett 31:47–52

    Google Scholar 

  • Goldstein A (1964) Wakefulness caused by caffeine. Naunyn Schmiedeberg's Arch Exp Pathol Pharmakol 248:269–278

    Google Scholar 

  • Goldstein A, Kaizer S (1969) 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, Warren R (1965a) Psychotropic effects of caffeine in man. II. Alertness, psychomotor coordination, and mood. J Pharmacol Exp Ther 150:146–151

    Google Scholar 

  • Goldstein A, Warren R, Kaizer S (1965b) Psychotropic effects of caffeine in man. I. Individual differences in sensitivity to caffeine-induced wakefulness. J Pharmacol Exp Ther 149:156–159

    Google Scholar 

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

    Google Scholar 

  • Goldstein A, Aronow L, Kalman SM (1974) Principles of drug action: The basis of pharmacology, 2nd edn. Wiley, New York

    Google Scholar 

  • Graham DM (1978) Caffeine — its identity, dietary sources, intake and biological effects. Nutr Rev 36:97–102

    Google Scholar 

  • Granella F, Farina S, Malferrari G, Manzoni GC (1987) Drug abuse in chronic headache: a clinico-epidemiologic study. Cephalalgia 7:15–19

    Article  CAS  PubMed  Google Scholar 

  • Greden JF (1974) Anxiety or caffeinism: A diagnostic dilemma. Am J Psychiatry 131:1089–1092

    Google Scholar 

  • Greden JF (1980) Caffeine and tobacco dependence. In: Kaplan HI, Freedman AM, Sadock BJ (eds) Comprehensive textbook of psyciatry/III, vol 2, 3rd edn. Williams & Wilkins, Baltimore London, pp 1645–1652

    Google Scholar 

  • Greden JF (1981) Caffeinism and caffeine withdrawal. In: Lowinson JH, Ruiz P (eds) Substance abuse: clinical problems and perspectives. Williams & Wilkins, Baltimore London, pp 274–286

    Google Scholar 

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

    Google Scholar 

  • Greden JF, Victor BS, Fontaine P, Lubetsky M (1980) Caffeine-withdrawal headache: A clinical profile. Psychosomatics 21:411–413; 417–418

    Google Scholar 

  • Green RM, Stiles GL (1986) Chronic caffeine ingestion sensitizes the A1 adenosine receptor-adenylate cyclase system in rat cerebral cortex. J Clin Invest 77:222–227

    Google Scholar 

  • Griffiths RR, Woodson PP (1987) Reinforcing properties of cafeine: studies in humans and laboratory animals. Pharmacol Biochem Behav (in press)

  • 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 163–208

    Google Scholar 

  • Griffiths RR, Bigelow GE, Henningfield JE (1980) Similarities in animal and human drug-taking behavior. In: Mello NK (ed) Advances in substance abuse, vol 1, JAI Press, Greenwich, Connecticut, pp 1–90

    Google Scholar 

  • Griffiths RR, Lamb RJ, Ator NA, Roache JD, Brady JV (1985) Relative abuse liability of triazolam: experimental assessment in animals and humans. Neurosci Biobehav Rev 9:133–151

    Google Scholar 

  • Griffiths RR, Bigelow GE, Liebson IA (1986a) Human coffee drinking: reinforcing and physical dependence producing effects of caffeine. J Pharmacol Exp Ther 239:416–425

    Google Scholar 

  • Griffiths RR, Bigelow GE, Liebson IA, O'Keeffe M, O'Leary D, Russ N (1986b) Human coffee drinking: manipulation of concentration and caffeine dose. J Exp Anal Behav 45:133–148

    Google Scholar 

  • Guelliot O (1885a) Du caféisme chronique. Union Med Sci Nordest 9:181–194

    Google Scholar 

  • Guelliot O (1885b) Du caféisme chronique. Union Med Sci Nordest 9:221–240

    Google Scholar 

  • Guelliot O (1887) Le caféisme. J Prat Rev Gen Clin Ther 1:677–680

    Google Scholar 

  • Harrie JR (1970) Caffeine and headache. JAMA 213:628

    Google Scholar 

  • Hirsh, K (1984) Central nervous system pharmacology of the dietary methylxanthines. In: Spiller GA (ed) The methylxanthine beverages and foods: Chemistry, consumption, and health effects, Liss, New York, pp 235–301

    Google Scholar 

  • Hollingworth, HL (1912) The influence of caffein on mental and motor efficiency, Arch Psychol (No. 22), 1–166. In: Woodworth RS (ed) Columbia contributions to philosophy and psychology, vol 20, no. 4. The Science Press, New York

    Google Scholar 

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

    Google Scholar 

  • Holtzman SG (1987) Discriminative stimulus effects of caffeine: tolerance and cross-tolerance with methylphenidate. Life Sci 40:381–389

    Google Scholar 

  • Holtzman SG, Finn IB (1987) Tolerance to behavioral effects of caffeine in rats. Pharmacol Biochem Behav (in press)

  • Horowitz DA, Jablonski W, Mehta KA (1982) Apnea associated with theophylline withdrawal in a term neonate. Am J Dis Child 136:73–74

    Google Scholar 

  • Horst K, Buxton RE, Robinson WD (1934) The effect of the habitual use of coffee or decaffeinated coffee upon blood pressure and certain motor reactions of normal young men. J Pharmacol Exp Ther 52:322–337

    Google Scholar 

  • Hyner GC (1979) Relaxation as principal treatment for excessive cigarette use and caffeine ingestion by a college female. Psychol Rep 45:531–534

    Google Scholar 

  • Ideström C-M (1960) Fenacetin-fenazon-coffein tillvänjning: En experimentell studie. Nord Med 64:1484–1487

    Google Scholar 

  • In Der Beeck M (1961) Kaffeesucht und Koffeinismus: Zugleich ein literarischer Beitrag zur Definition der Sucht. Ther Monats 7:232–237

    Google Scholar 

  • Isbell H, Wilker A, Eisenman AJ, Daingerfield M, Frank K (1948) Liability of addiction to 6-dimethylamino-4–4-diphenyl-3-heptanone (methadon, “amidone” or “10820”) in man. Arch Intern Med 82:362–392

    Google Scholar 

  • James JE, Stirling KP, Hampton BAM (1985) Caffeine fading: behavioral treatment of caffeine abuse. Behav Ther 16:15–27

    Google Scholar 

  • James JE, Paull I, Cameron-Traub E (1987) Biochemical validation of self-reported caffeine consumption during caffeine fading. J Behav Med (in press)

  • Kalow W (1985) Variability of caffeine metabolism in humans. Arzneimittelforschung 35(I):319–324

    Google Scholar 

  • Khoury GC, Maltbie AA (1984) Caffeine — a drug with multiple points of entry. NC Med J 45:225–226

    Google Scholar 

  • Kielholz P (1970) Present problems of drug dependence in Switzerland. Bull Narc 12(2):1–6

    Google Scholar 

  • King E (1903) Tea and coffee intoxication. Am Med 5:182–183

    Google Scholar 

  • Kingdon (1833) Effects of tea and coffee drinking. Lancet II:47–48

    Google Scholar 

  • Kolb L (1927) Clinical contribution to drug addiction: the struggle for cure and the conscious reasons for relapse. J Nerv Ment Dis 66:22–43

    Google Scholar 

  • Kozlowski LT (1976) Effect of caffeine on coffee drinking. Nature 264:354–355

    Google Scholar 

  • Laux G (1979) Ein Fall von Akrinor®-Sucht. Nervenarzt 50:121–123

    Google Scholar 

  • Logan L, Seale TW, Carney JM (1986) Inherent differences in sensitivity to methylxanthines among inbred mice. Pharmacol Biochem Behav 24:1281–1286

    Google Scholar 

  • Mackenzie TB, Popkin MK, Dziubinski J, Sheppard JR (1981) Effects of caffeine withdrawal on isoproterenol-stimulated cyclic adenosine monophosphate. Clin Pharmacol Ther 30:436–438

    Google Scholar 

  • Marangos PJ, Boulenger J-P, Patel J (1984) Effects of chronic caffeine on brain adenosine receptors: Regional and ontogenetic studies. Life Sci 34:899–907

    Google Scholar 

  • Marburg O (1899) Ueber einen Fall von Spätepilepsie bei einer Kaffeebohnenesserin. Wien Klin Rundsch 13:337–339

    Google Scholar 

  • Martin WR (ed) (1977) Drug addiction I: Morphine, sedative/hypnotic and alcohol dependence. Handbook of experimental pharmacology, vol 45/I, Heffter-Heubner New Series, Springer, Berlin Heidelberg New York

    Google Scholar 

  • Mathew RJ, Wilson WH (1985) Caffeine consumption, withdrawal and cerebral blood flow. Headache 25:305–309

    CAS  PubMed  Google Scholar 

  • McNair DM, Lorr M, Droppleman LF (1971) Profile of mood states (manual). Educational and Industrial Testing Service, San Diego, California

    Google Scholar 

  • Mendel F (1889) Die schädlichen Folgen des chronischen Kaffeemissbrauchs. Berl Klin Wochenschr 26:877–880

    Google Scholar 

  • Miller JL (1960) Caffeine, chocolate and withdrawal headaches. Northwest Med 59:502–504

    Google Scholar 

  • Molde DA (1975) Diagnosing caffeinism. Am J Psychiatry 132:202

    Google Scholar 

  • Murray RM (1973) Dependence on analgesics in analgesic nephropathy. Br J Addict 68:265–272

    Google Scholar 

  • Naismith DJ, Akinyanju PA, Szanto S, Yudkin J (1970) The effect in volunteers of coffee and decaffeinated coffee on blood glucose, insulin, plasma lipids and some factors involved in blood clotting. Nutr Metab 12:144–151

    Google Scholar 

  • Newman RG (1983) The need to redefine “addiction.” N Engl J Med 308:1096–1098

    Google Scholar 

  • Petursson H, Lader M (1984) Dependence on tranquillizers. In: Russell G, Marley E, Williams P (eds) Institute of Psychiatry Maudsley monographs, no 28. Oxford University Press, Oxford

    Google Scholar 

  • Podboy J, Malloy W (1977) Caffeine reduction and behavior changes in the severely retarded. Ment Retard 15:40

    Google Scholar 

  • Rainey JT (1985) Headache related to chronic caffeine addiction. Tex Dent J 102:29–30

    Google Scholar 

  • Rall TW (1985) Central nervous system stimulants [continued]: The methylxanthines. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) Goodman and Gilman's the pharmacological basis of therapeutics, 7th edn. Macmillan, New York, pp 589–603

    Google Scholar 

  • Rapoport JL, Jensvold M, Elkins R, Buchsbaum MS, Weingartner H, Ludlow C, Zahn TP, Berg CJ, Neims AH (1981) Behavioral and cognitive effects of caffeine in boys and adult males. J Nerv Ment Dis 169:726–732

    Google Scholar 

  • Reimann HA (1967) Caffeinism: A cause of long-continued, low-grade fever. JAMA 202:131–132

    Google Scholar 

  • Rippere V (1984) Some varieties of food intolerance in psychiatric patients: An overview. Nutr Health 3:125–136

    Google Scholar 

  • Robertson D, Wade D, Workman R, Woosley RL, Oates JA (1981) Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Invest 67:1111–1117

    Google Scholar 

  • Roch M (1914) Société médicale de Genève, Séance du 4 février 1914. Rev Med Suisse Romande 34:217–219

    Google Scholar 

  • Roch M (1916) Le caféisme chronique. Arch Mal Coeur 9:19–33

    Google Scholar 

  • Roller L (1981) Caffeinism: Subjective quantitative aspect of withdrawal syndrome. Med J Aust 1:146

    Google Scholar 

  • Ross BD (1971) Caffeine and fluid retention. JAMA 218:596

    Google Scholar 

  • Rugh JT (1896) Profound toxic effects from the drinking of large amounts of strong coffee. Med Surg Rep 75:549–550

    Google Scholar 

  • Schilling V (1928) Über einen als Herzfehler erscheinenden Fall von “Innenkörperanämie”, aufgedeckt als chronische Antife-brinvergiftung und Coffeinsucht. Z Klin Med 108:709–736

    Google Scholar 

  • Schlesinger H (1931) Verhandlungen ärztlicher Gesellschaften und Kongreßberichte: Offizielles Protokoll der Gesellschaft der Aerzte in Wien, Sitzung vom 8. Mai 1931. Wien Klin Wochenschr 44:657

    Google Scholar 

  • Schulte D (1950) Ungewöhnliche Folgen nach Coffeingenuß. Ber Zusammenkunft Dtsch Ophthalmol Ges 55:406–408 (Demonstrations-Sitzung Nr 28)

    Google Scholar 

  • Seale TW, Abla KA, Cao W, Parker KM, Rennert OM, Carney JM (1986) Inherent hyporesponsiveness to methylxanthine-induced behavioral changes associated with supersensitivity to 5'-N-ethylcarboxamidoadenosine (NECA). Pharmacol Biochem Behav 25:1271–1277

    Google Scholar 

  • Shorofsky MA, Lamm N (1977) Caffeine-withdrawal headache and fasting. NY State J Med 77:217–218

    Google Scholar 

  • Snyder SH (1985) Adenosine as a neuromodulator. Annu Rev Neurosci 8:103–124

    Google Scholar 

  • Stoffer SS (1979) Coffee consumption. Arch Intern Med 139:1194–1195

    Google Scholar 

  • Stransky E (1932) Zur Frage des Coffeinismus. Wien Med Wochenschr 82:395–398

    Google Scholar 

  • Victor BS, Lubetsky M, Greden JF (1981) Somatic manifestations of caffeinism. J Clin Psychiatry 42:185–188

    Google Scholar 

  • Vitiello MV, Woods SC (1977) Evidence for withdrawal from caffeine by rats. Pharmacol Biochem Behav 6:553–555

    Google Scholar 

  • Vojtěchovský M, Šafratová V (1972) Comparative study of caffeine with other stimulants in university students. Act Nerv Super 14:138–139

    Google Scholar 

  • Von Borstel RW, Wurtman RJ, Conlay LA (1983) Chronic caffeine consumption potentiates the hypotensive action of circulating adenosine. Life Sci 32:1151–1158

    Google Scholar 

  • Wagner W (1939) Kaffee, ein Rauschmittel. Nervenarzt 12:296–301

    Google Scholar 

  • Weil A, Rosen W (1983) Chocolate to morphine: Understanding mind-active drugs. Houghton Mifflin Company, Boston

    Google Scholar 

  • Weiss B, Laties VG (1962) Enhancement of human performance by caffeine and the amphetamines. Pharmacol Rev 14:1–36

    CAS  PubMed  Google Scholar 

  • White BC, Lincoln CA, Pearce NW, Reeb R, Vaida C (1980) Anxiety and muscle tension as consequences of caffeine withdrawal. Science 209:1547–1548

    Google Scholar 

  • Wilkin JK (1986) The caffeine withdrawal flush: Report of a case of “weekend flushing”. Milit Med 151:123–124

    Google Scholar 

  • Winstead DK (1976) Coffee consumption among psychiatric inpatients. Am J Psychiatry 133:1447–1450

    Google Scholar 

  • Young JJ, Brownlee HJ, Delaney R (1982) Caffeine and burning feet. Drug Intell Clin Pharm 16:779–780

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Griffiths, R.R., Woodson, P.P. Caffeine physical dependence: a review of human and laboratory animal studies. Psychopharmacology 94, 437–451 (1988). https://doi.org/10.1007/BF00212836

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00212836

Key words

  • Caffeine
  • Caffeinism
  • Coffee
  • Tea
  • Physical dependence
  • Withdrawal
  • Reinforcer
  • Drug self-administration
  • Subjective effects
  • Drug dependence
  • Drug abuse
  • Humans
  • Animals