Genetics of caffeine consumption and responses to caffeine



Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine.


This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers.


Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of polysubstance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users.


Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.

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

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.


  1. Abraham J, Mudd JO, Kapur N, Klein K, Champion HC, Wittstein IS (2009) Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists. J Am Coll Cardiol 53:1320–1325

  2. Alsene K, Deckert J, Sand P, de Wit H (2003) Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 28:1694–1702

  3. Andersen LF, Jacobs DR Jr, Carlsen MH, Blomhoff R (2006) Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study. Am J Clin Nutr 83:1039–1046

  4. Arias Horcajadas F, Sánchez Romero S, Padìn Calo J, Fernández-Rojo S, Fernández Martìn G (2005) Psychoactive drugs use in patients with panic disorder. Actas Esp Psiquiatr 33:160–164

  5. Arnaud MJ (1987) The pharmacology of caffeine. Prog Drug Res 31:273–313

  6. Ascherio A, Zhang SM, Hernán MA, Kawachi I, Colditz GA, Speizer FE, Willett WC (2001) Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 50:56–63

  7. Bchir F, Dogui M, Ben Fradj R, Arnaud MJ, Saguem S (2006) Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects. CR Biol 329:512–519

  8. Benowitz NL (1990) Clinical pharmacology of caffeine. Annu Rev Med 41:277–288

  9. Berthou F, Goasduff T, Dréano Y, Ménez J-F (1995) Caffeine increases its own metabolism through cytochrome P4501A induction in rats. Life Sci 57:541–549

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

  11. Bruce M, Scott N, Shine P, Lader M (1992) Anxiogenic effects of caffeine in patients with anxiety disorders. Arch Gen Psychiatry 49:867–869

  12. Carmelli D, Swan GE, Robinette D, Fabsitz RR (1990) Heritability of substance use in the NAS-NRC Twin Registry. Acta Genet Med Gemellol (Roma) 39:91–98

  13. Carter AJ, O’Connor WT, Carter MJ, Ungerstedt U (1995) Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors. J Pharmacol Exp Ther 273:637–642

  14. Cauli O, Morelli M (2005) Caffeine and the dopaminergic system. Behav Pharmacol 16:63–77

  15. Charney DS, Heninger GR, Jatlow PI (1985) Increased anxiogenic effects of caffeine in panic disorders. Arch Gen Psychiatry 42:233–243

  16. Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD (2002) Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 155:732–738

  17. Chen J-F, Xu K, Petzer JP, Staal R, Xu Y-H, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N Jr, Schwarzschild MA (2001) Neuroprotection by caffeine and A2A adenosine receptor inactivation in a model of Parkinson’s disease. J Neurosci 21:143RC

  18. Childs E, Hohoff C, Deckert J, Xu K, Badner J, de Wit H (2008) Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology 33:2791–2800

  19. Ciruela F, Casado V, Rodrigues RJ, Lujan R, Burgueno J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortes A, Canela EI, Lopez-Gimenez JF, Milligan G, Lluis C, Cunha RA, Ferre S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1–A2A receptor heteromers. J Neurosci 26:2080–2087

  20. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (2006) Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141

  21. Cornelis MC, El-Sohemy A, Campos H (2007) Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am J Clin Nutr 86:240–244

  22. Daly JW, Fredholm BB (1998) Caffeine—an atypical drug of dependence. Drug Alcohol Depend 51:199–206

  23. Daly JW, Buttslamb P, Padgett W (1983) Subclasses of adenosine receptors in the central nervous-system—interaction with caffeine and related methylxanthines. Cell Mol Neurobiol 3:69–80

  24. Deckert J, Nothen MM, Franke P, Delmo C, Fritze J, Knapp M, Maier W, Beckmann H, Propping P (1998) Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease. Mol Psychiatry 3:81–85

  25. Devonshire HW, Kong I, Cooper M, Sloan TP, Idle JR, Smith RL (1983) The contribution of genetically determined oxidation status to inter-individual variation in phenacetin disposition. Br J Clin Pharmacol 16:157–166

  26. Dhaenens CM, Burnouf S, Simonin C, Van Brussel E, Duhamel A, Defebvre L, Duru C, Vuillaume I, Cazeneuve C, Charles P, Maison P, Debruxelles S, Verny C, Gervais H, Azulay JP, Tranchant C, Bachoud-Levi AC, Durr A, Buee L, Krystkowiak P, Sablonniere B, Blum D (2009) A genetic variation in the ADORA2A gene modifies age at onset in Huntington’s disease. Neurobiol Dis 35:474–476

  27. Dunwiddie TV, Masino SA (2001) The role and regulation of adenosine in the central nervous system. Annu Rev Neurosci 24:31–55

  28. El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois J-M (2005) Reduced appetite for caffeine in adenosine A2A receptor knockout mice. Eur J Pharmacol 519:290–291

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

  30. Facheris MF, Schneider NK, Lesnick TG, Md A, Cunningham JM, Rocca WA, Maraganore DM (2008) Coffee, caffeine-related genes, and Parkinson’s disease: a case-control study. Mov Disord 23:2033–2040

  31. Farag NH, Vincent AS, McKey BS, Whitsett TL, Lovallo WR (2005) Hemodynamic mechanisms underlying the incomplete tolerance to caffeine’s pressor effects. Am J Cardiol 95:1389–1392

  32. Fenu S, Cauli O, Morelli M (2000) Cross-sensitization between the motor activating effects of bromocriptine and caffeine: role of adenosine A2A receptors. Behav Brain Res 114:97–105

  33. Ferre S (2008) An update on the mechanisms of the psychostimulant effects of caffeine. J Neurochem 105:1067–1079

  34. Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14:186–195

  35. Fisone G, Borgkvist A, Usiello A (2004) Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci 61:857–872

  36. Frary CD, Johnson RK, Wang MQ (2005) Food sources and intakes of caffeine in the diets of persons in the United States. J Am Diet Assoc 105:110–113

  37. Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51:83–133

  38. Fuxe K, Agnati LF, Jacobsen K, Hillion J, Canals M, Torvinen M, Tinner-Staines B, Staines W, Rosin D, Terasmaa A, Popoli P, Leo G, Vergoni V, Lluis C, Ciruela F, Franco R, Ferre S (2003) Receptor heteromerization in adenosine A2A receptor signaling: relevance for striatal function and Parkinson’s disease. Neurology 61:19S–23S

  39. Garrett BE, Griffiths RR (1997) The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol Biochem Behav 57:533–541

  40. Griffiths RR, Woodson PP (1988) Reinforcing effects of caffeine in humans. J Pharmacol Exp Ther 246:21–29

  41. Grosso LM, Bracken MB (2005) Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure assessment considerations during pregnancy. Ann Epidemiol 15:460–466

  42. Gunes A, Dahl ML (2008) Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Pharmacogenomics 9:625–637

  43. Hamilton SP, Slager SL, De Leon AB, Heiman GA, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA (2004) Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder. Neuropsychopharmacology 29:558–565

  44. Hansen JL, Reed DR, Wright MJ, Martin NG, Breslin PA (2006) Heritability and genetic covariation of sensitivity to PROP, SOA, quinine HCl, and caffeine. Chem Senses 31:403–413

  45. Happonen P, Voutilainen S, Tuomainen TP, Salonen JT (2006) Catechol-o-methyltransferase gene polymorphism modifies the effect of coffee intake on incidence of acute coronary events. PLoS ONE 1:e117

  46. Hartley TR, Sung BH, Pincomb GA, Whitsett TL, Wilson MF, Lovallo WR (2000) Hypertension risk status and effect of caffeine on blood pressure. Hypertension 36:137–141

  47. Haskell CF, Kennedy DO, Wesnes KA, Scholey AB (2005) Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology (Berl) 179:813–825

  48. Hettema JM, Corey LA, Kendler KS (1999) A multivariate genetic analysis of the use of tobacco, alcohol, and caffeine in a population based sample of male and female twins. Drug Alcohol Depend 57:69–78

  49. Hohoff C, McDonald JM, Baune BT, Cook EH, Deckert J, de Wit H (2005) Interindividual variation in anxiety response to amphetamine: possible role for adenosine A2A receptor gene variants. Am J Med Genet B Neuropsychiatr Genet 139B:42–44

  50. Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O (2005) Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8:858–859

  51. Jee SH, He J, Whelton PK, Suh I, Klag MJ (1999) The effect of chronic coffee drinking on blood pressure: a meta-analysis of controlled clinical trials. Hypertension 33:647–652

  52. Kalow W, Tang BK (1991) Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 50:508–519

  53. Kashuba AD, Bertino JS Jr, Kearns GL, Leeder JS, James AW, Gotschall R, Nafziger AN (1998) Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping. Clin Pharmacol Ther 63:540–551

  54. Kawachi I, Colditz GA, Stone CB (1994) Does coffee drinking increase the risk of coronary heart disease? Results from a meta-analysis. Br Heart J 72:269–275

  55. Kendler KS (1993) Twin studies of psychiatric illness: current status and future directions. Arch Gen Psychiatry 50:905–915

  56. Kendler KS, Prescott CA (1999) Caffeine intake, tolerance, and withdrawal in women: a population-based twin study. Am J Psychiatry 156:223–228

  57. Kendler KS, Heath AC, Martin NG, Eaves LJ (1987) Symptoms of anxiety and symptoms of depression: same genes, different environments? Arch Gen Psychiatry 44:451–457

  58. Kendler KS, Myers J, Prescott CA (2007) Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Arch Gen Psychiatry 64:1313–1320

  59. Kendler KS, Schmitt E, Aggen SH, Prescott CA (2008) Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry 65:674–682

  60. Kirk IP, Richardson PJ (1994) Adenosine A2a receptor-mediated modulation of striatal GABA and acetylcholine release. J Neurochem 62:960–966

  61. Klatsky AL, Friedman GD, Armstrong MA (1990) Coffee use prior to myocardial infarction restudied: heavier intake may increase the risk. Am J Epidemiol 132:479–488

  62. Kuribara H (1994) Modification by caffeine of the sensitization to methamphetamine and cocaine in terms of ambulation in mice. Life Sci 55:933–940

  63. Kurokawa M, Shiozaki S, Nonaka H, Kase H, Nakamura J, Kuwana Y (1996) In vivo regulation of acetylcholine release via adenosine A1 receptor in rat cerebral cortex. Neurosci Lett 209:181–184

  64. Laitala VS, Kaprio J, Silventoinen K (2008) Genetics of coffee consumption and its stability. Addiction 103:2054–2061

  65. Lam P, Hong CJ, Tsai SJ (2005) Association study of A2a adenosine receptor genetic polymorphism in panic disorder. Neurosci Lett 378:98–101

  66. Lane JD, Adcock RA, Williams RB, Kuhn CM (1990) Caffeine effects on cardiovascular and neuroendocrine responses to acute psychosocial stress and their relationship to level of habitual caffeine consumption. Psychosom Med 52:320–336

  67. Lee MA, Cameron OG, Greden JF (1985) Anxiety and caffeine consumption in people with anxiety disorders. Psychiatry Res 15:211–217

  68. Lee M, Flegel P, Greden J, Cameron O (1988) Anxiogenic effects of caffeine on panic and depressed patients. Am J Psychiatry 145:632–635

  69. Lelo A, Birkett DJ, Robson RA, Miners JO (1986) Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. Br J Clin Pharmacol 22:177–182

  70. LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM (2008) Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 63:295–302

  71. Lieberman HR, Wurtman RJ, Emde GG, Roberts C, Coviella ILG (1987) The effects of low doses of caffeine on human performance and mood. Psychopharmacology 92:308–312

  72. Lieberman HR, Tharion WJ, Shukitt-Hale B, Speckman KL, Tulley R (2002) Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea–Air–Land. Psychopharmacology (Berl) 164:250–261

  73. Lovallo WR, Wilson MF, Vincent AS, Sung BH, McKey BS, Whitsett TL (2004) Blood pressure response to caffeine shows incomplete tolerance after short-term regular consumption. Hypertension 43:760–765

  74. Luciano M, Kirk KM, Heath AC, Martin NG (2005) The genetics of tea and coffee drinking and preference for source of caffeine in a large community sample of Australian twins. Addiction 100:1510–1517

  75. Luciano M, Zhu G, Kirk KM, Gordon SD, Heath AC, Montgomery GW, Martin NG (2007) “No thanks, it keeps me awake”: the genetics of coffee-attributed sleep disturbance. Sleep 30:1378–1386

  76. Maia L, de Mendonca A (2002) Does caffeine intake protect from Alzheimer’s disease? Eur J Neurol 9:377–382

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

  78. Marchi M, Raiteri L, Risso F, Vallarino A, Bonfanti A, Monopoli A, Ongini E, Raiteri M (2002) Effects of adenosine A1 and A2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes. Br J Pharmacol 136:434–440

  79. Martinez-Mir MI, Probst A, Palacios JM (1991) Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease. Neuroscience 42:697–706

  80. Merica H (1998) Spectral characteristics of sleep EEG in chronic insomnia. Eur J Neurosci 10:1826–1834

  81. Migliardi JR, Armellino JJ, Friedman M, Gillings DB, Beaver WT (1994) Caffeine as an analgesic adjuvant in tension headache. Clin Pharmacol Ther 56:576–586

  82. Miners JO, Birkett DJ (1996) The use of caffeine as a metabolic probe for human drug metabolizing enzymes. Gen Pharmacol 27:245–249

  83. Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (1998) Blockade of adenosine A2A receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats. NeuroReport 9:3955–3959

  84. Mosqueda-Garcia R, Robertson D, Robertson RM (1993) The cardiovascular effects of caffeine. In: Garattini S (ed) Caffeine, coffee, and health. Raven, New York, pp 157–176

  85. Nardi AE, Lopes FL, Freire RC, Veras AB, Nascimento I, Valença AM, de-Melo-Neto VL, Soares-Filho GL, King AL, Araùjo DM, Mezzasalma MA, Rassi A, Zin WA (2009) Panic disorder and social anxiety disorder subtypes in a caffeine challenge test. Psychiatry Res 169:149–153

  86. Neale MC, Cardon LR (1992) Methodology for genetic studies of twins and families. Kluwer, London

  87. Noble EP (2000) Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene: a review. Eur Psychiatry 15:79–89

  88. Noordzij M, Uiterwaal CS, Arends LR, Kok FJ, Grobbee DE, Geleijnse JM (2005) Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens 23:921–928

  89. Nurminen ML, Niittynen L, Korpela R, Vapaatalo H (1999) Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 53:831–839

  90. Obase Y, Shimoda T, Kawano T, Saeki S, S-y T, Mitsuta-Izaki K, Matsuse H, Kinoshita M, Kohno S (2003) Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma. Clin Pharmacol Ther 73:468–474

  91. Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis ME (2005) Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci (Lond) 109:55–60

  92. Perlis ML, Merica H, Smith MT, Giles DE (2001) Beta EEG activity and insomnia. Sleep Med Rev 5:365–376

  93. Popoli P, Blum D, Domenici MR, Burnouf S, Chern Y (2008) A critical evaluation of adenosine A2A receptors as potentially “druggable” targets in Huntington’s disease. Curr Pharm Des 14:1500–1511

  94. Rasmussen BB, Brix TH, Kyvik KO, Brøsen K (2002) The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenet Genomics 12:473–478

  95. Retey JV, Adam M, Khatami R, Luhmann UF, Jung HH, Berger W, Landolt HP (2007) A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther 81:692–698

  96. Riksen NP, Rongen GA, Smits P (2009) Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol Ther 121:185–191

  97. 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

  98. Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung K-H, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674–2679

  99. Sachse C, Brockmöller J, Bauer S, Roots I (1999) Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 47:445–449

  100. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W, the Caffeine for Apnea of Prematurity Trial Group (2007) Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 357:1893–1902

  101. Shahidi NT (1967) Acetophenetidin sensitivity. Am J Dis Child 113:81–82

  102. Shi D, Nikodijević O, Jacobson KA, Daly JW (1993) Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain. Cell Mol Neurobiol 13:247–261

  103. Silverman K, Griffiths RR (1992) Low-dose caffeine discrimination and self-reported mood effects in normal volunteers. J Exp Anal Behav 57:91–107

  104. Smits P, Thien T, Van ’t Laar A (1985) The cardiovascular effects of regular and decaffeinated coffee. Br J Clin Pharmacol 19:852–854

  105. Sofi F, Conti AA, Gori AM, Eliana Luisi ML, Casini A, Abbate R, Gensini GF (2007) Coffee consumption and risk of coronary heart disease: a meta-analysis. Nutr Metab Cardiovasc Dis 17:209–223

  106. Swan GE, Carmelli D, Cardon LR (1996) The consumption of tobacco, alcohol, and coffee in Caucasian male twins: a multivariate genetic analysis. J Subst Abuse 8:19–31

  107. Swan GE, Carmelli D, Cardon LR (1997) Heavy consumption of cigarettes, alcohol and coffee in male twins. J Stud Alcohol 58:182–190

  108. Swanson JA, Lee JW, Hopp JW (1994) Caffeine and nicotine: a review of their joint use and possible interactive effects in tobacco withdrawal. Addict Behav 19:229–256

  109. Tan EK, Lu ZY, Fook-Chong SMC, Tan E, Shen H, Chua E, Yih Y, Teo YY, Zhao Y (2006) Exploring an interaction of adenosine A2A receptor variability with coffee and tea intake in Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 141B:634–636

  110. Teucher B, Skinner J, Skidmore PM, Cassidy A, Fairweather-Tait SJ, Hooper L, Roe MA, Foxall R, Oyston SL, Cherkas LF, Perks UC, Spector TD, MacGregor AJ (2007) Dietary patterns and heritability of food choice in a UK female twin cohort. Twin Res Hum Genet 10:734–748

  111. Vink JM, Staphorsius AS, Boomsma DI (2009) A genetic analysis of coffee consumption in a sample of Dutch twins. Twin Res Hum Genet 12:127–131

  112. Yabuuchi K, Kuroiwa M, Shuto T, Sotogaku N, Snyder GL, Higashi H, Tanaka M, Greengard P, Nishi A (2006) Role of adenosine A1 receptors in the modulation of dopamine D1 and adenosine A2A receptor signaling in the neostriatum. Neuroscience 141:19–25

  113. Yamada K, Hattori E, Shimizu M, Sugaya A, Shibuya H, Yoshikawa T (2001) Association studies of the cholecystokinin B receptor and A2a adenosine receptor genes in panic disorder. J Neural Transm 108:837–848

  114. Zahniser NR, Simosky JK, Mayfield RD, Negri CA, Hanania T, Larson GA, Kelly MA, Grandy DK, Rubinstein M, Low MJ, Fredholm BB (2000) Functional uncoupling of adenosine A2A receptors and reduced response to caffeine in mice lacking dopamine D2 receptors. J Neurosci 20:5949–5957

Download references


This research was supported by NIDA (DA021336 and DA02812). All authors reported no biomedical interests or potential conflicts of interest.

Author information

Correspondence to Harriet de Wit.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yang, A., Palmer, A.A. & de Wit, H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology 211, 245–257 (2010) doi:10.1007/s00213-010-1900-1

Download citation


  • Caffeine
  • Adenosine
  • Dopamine
  • Genetic polymorphism
  • CYP1A2
  • Parkinson’s cardiovascular disease