Subscribe to RSS
DOI: 10.1055/a-0985-4236
Koffein, das am häufigsten konsumierte Psychostimulans: eine narrative Übersichtsarbeit
Caffeine, the most frequently consumed psychostimulant: a narrative review article![](https://www.thieme-connect.de/media/fdn/202005/lookinside/thumbnails/10.1055a-0985-4236-1.jpg)
Zusammenfassung
Koffein ist das weltweit am häufigsten konsumierte Psychostimulans. Es ist nahezu unbeschränkt verfügbar und unterliegt in Europa keiner staatlichen Regulation. Neben seiner primären Rolle als Inhalts- oder Zusatzstoff in zahlreichen Getränken findet es auch medizinische Verwendung in der adjuvanten Schmerztherapie, bei primärem Atemstillstand bei Neugeborenen und es ist zugelassen für die kurzfristige Beseitigung von Ermüdungserscheinungen. Der Wirkmechanismus von Koffein als Psychostimulans in typischerweise aufgenommen Dosierungen basiert vermutlich in erster Linie auf einem zentralen Antagonismus von Adenosinrezeptoren (A1- und A2A-Rezeptoren), was zu einer zentralen Hemmung der Adenosin-vermittelten Reduktion der Aktivität des dopaminergen und aufsteigenden Aktivierungssystems führt. Die Metabolisierung von Koffein ist hautsächlich abhängig von Cytochrom P450 1A2, sodass Faktoren, die die Aktivität von CYP 1A2 beeinflussen (z. B. Medikamente, Schwangerschaft), erhebliche Veränderungen der pharmakokinetischen Parameter induzieren können. Koffein führt insbesondere bei Individuen mit Schlafentzug zu einer Verbesserung der Vigilanz, Aufmerksamkeit und Reaktionszeit. Zudem kann es sportliche Ausdauerleistungen und muskuläre Kraft verbessern. Intoxikationen mit Koffein sind selten, können jedoch letal verlaufen. In üblicherweise aufgenommenen Mengen gilt Koffeingebrauch als nicht gesundheitsschädlich. Koffein weist zahlreiche, jedoch nicht alle Merkmale einer Substanz mit „Abhängigkeitspotential“ auf; Entzugssyndrome nach Beendigung einer längeren Anwendung und Toleranz sind bekannt. Im DSM-5 wird die „Koffeingebrauchsstörung“ als mögliche künftige Störung, die gegenwärtig weiterer Forschung bedarf, rubriziert. Das Koffeingebrauchsmuster von Patienten sollte im Rahmen der ärztlichen Tätigkeit berücksichtigt werden.
Abstract
Caffeine is the worldwide most frequently consumed psychostimulant. Its availability is nearly unlimited and in Europe it is not subject to state regulation. Apart from its primary role as an ingredient or additive in numerous beverages it also has medical use in apnea of prematurity, as an adjuvant in pain therapy and has regulatory approval for the short-term treatment of symptoms of fatigue. In doses typically administered caffeine’s mechanism of action as a psychostimulant is presumably primarily based on central antagonism at adenosine receptors (A1- und A2A-receptors), which facilitates central inhibition of adenosine-mediated reduction of the activity of the dopaminergic and ascending arousal system. Metabolisation of caffeine mainly depends on cytochrome P450 1A2. Thus, factors that influence the activity of CYP 1A2 (e. g. medication, pregnancy), may induce remarkable changes of pharmacokinetic parameters. Caffeine improves vigilance, attention and reaction time, particularly in sleep-deprived individuals. Moreover, it may improve endurance performances in sports and muscle strength. Intoxications with caffeine are rare, however can be fatal. In general, caffeine use seems not harmful within typical doses of intake. Caffeine features several, however not all characteristics of potentially addictive drugs; withdrawal after termination of a longer period of use and tolerance are known. In the DSM-5 “caffeine use disorder” is categorized as a possible future disorder that currently needs further study. The pattern of caffeine use of patients should be considered in the medical practice.
Publication History
Received: 27 May 2019
Accepted: 28 July 2019
Article published online:
14 October 2019
© Georg Thieme Verlag KG
Stuttgart · New York
-
Literatur
- 1 Burrows T, Pursey K, Neve M. et al. What are the health implications associated with the consumption of energy drinks?. Nutrition Reviews 2013; 71: 135-148
- 2 Nehling A. Are we dependent upon coffe and caffeine? A review on human and animal data. Neuroscience & Biobehavioral Reviews 1999; 23: 563-576
- 3 Fredholm B. Notes on the history of caffeine use. Handbook of Experimantal Pharmacology 2011; 200: 1-9
- 4 Arab J, Blumberg L. Introduction to the proceedings of the fourth international scientific symposion on tea and human health. The Journal of Nutrition 2008; 138: 1526-1528
- 5 Mair V, Hoh E. The true history of tea. London: Thames Hudson; 2009
- 6 Heckmann M, Weil J, Gonzalez de Mejia E. Caffeine (1, 3, 7-trimethylxanthine) in foods: A comprehensive review on consumption, functionality, safety, and regulatory matters. Journal of Food Science 2010; 75: R77 - 87
- 7 Weinberg B, Bealer B. The World of Caffeine: The science and Culture of the World’s Most Oopular Drug. New York and London: Routledge; 2002
- 8 Gilbert R, Marshman J, Schwieder M. et al. Caffeine content of beverages as consumed. Canadian Medical Assocciation Journal 1976; 114: 205-208
- 9 Kaufmann K, Sachdeo R. Caffeinated beverages and dercreased seizure control. Seizure - European Journal of Epilepsy 2003; 12: 519-521
- 10 Ogawa H, Ueki N. Clinical importance of caffeine dependence and abuse. Psychiatry and Clincal Neurosciences 2007; 61: 263-268
- 11 Verster J, Koenig J. Caffeine intake and its source: A review of national representative studies. Crit Rev Food Sci Nutr 2018; May 24. 58 (08) : 1250-1259
- 12 Temple J. Review: Trends, safety, and recommendation for caffeine use in children and adolescents. Journal of the American Acaddemy of Child and Adolescent Psychiatry 2019; 58: 36-45
- 13 Ahluwalia N, Herrick K. Caffeine intake from food and beverage sources and trends among children and adolescents in the united states: Review of national quantitative studies from 1999 to 2011. Advanced Nutrition 2015; 6: 102-111
- 14 Barone J, Roberts H. Caffeine consumption. Food Chem Toxicol. 1996 Jan. 34. (1): 119–29
- 15 Frary C, Johnson R, Wang M. Food sources and intakes of caffeine in the diets f persons in the United States. J Am Diet Assoc. 2005 Jan; 105. (1): 110–3.
- 16 Drewnowski A, Rehm C. Sources of caffeine in diets of US children and adults: Trends by beverage typ and purchase location. Nutrients 2016; 8: 154
- 17 McCusker R, Goldberger B, Cone E. Caffeine content of speciality coffees. Journal of Analytical Toxicology 2003; 27: 520-522
- 18 Knight C, Knight I, Mitchell D. et al. Beverage caffein intake in US consumers and subpopulations of interests: Estimates from the Share of Intake Panel survey. Food and Chemical Toxicology 2004; 42: 1923-1930
- 19 Fredholm B, Battig K, Holmen J. et al. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmaceutical Reviews 1999; 51: 83-133
- 20 Nawrot P, Jordan S, Eastwood J. et al. Effects of caffeine on human health. Food Additives & Contaminants 2003; 20: 1-30
- 21 Lipton R, Diener H, Robbins M. et al. Caffeine in the management of patients with headache. The Journal of Headache and Pain 2017; 18: 107
- 22 Moore R, Wiffen P, Derry S. et al. Non-prescription (OTC) oral analgesics for acute pain - an overview of Cochrane reviews. Cochrane Database Syst Rev. 2015; Nov. 4 (11) : CD010794 DOI: 10.1002/14651858.CD010794.pub2.
- 23 Derry C, Derry S, Moore R. Caffeine as an analgesic adjuvant for acute pain in adults. Cochrane Database Syst Rev. 2014; Dec. 11 (12) : CD009281. DOI: 10.1002/14651858.CD009281.pub3.
- 24 Vliegenthart R, Miedema M, Hutten G. et al. High versus standard dose caffeine for apnoea: A systematic review. Archives of Disease in Childhood Fetal & Neonatal Edition 2018; 103: F523-F529
- 25 Picone S, Bedetta M, Paolilo P. Caffein citrate: When and for how long. A literatue review. The Journal of MaternalFetal & Neonatal Medicin 2012; 25 (Suppl 3): 11-14
- 26 Shenk E, Bondi D, Pellerite M. et al. Evaluation of Timing and Dsing of Caffeine Citrate in Preterm Neonates for the Prevention of Bronchopulmonary Dysplasia. The Journal of Pediatric Pharmacology and Therapeutics 2018; 23: 139-145
- 27 Kugelmann A, Durand M. A comprehensive approach to the prevention of bronchopulmonary dysplasia. Pediatric Pulmonolgy 2011; 46: 1153-1165
- 28 Gupta V, Lipsitz A. Orthostatic hypotension in the elderly: Diagnosis and treatment. Am J Med. 2007; 120 (10) : 841–7
- 29 Onrot J, Goldberg M, Biaggioni I. et al. Hemodynamic and humoral effects of caffeine. Therapeutic implications for postprandial hypotension. The New English Journal of Medicin 1985; 313: 549-554
- 30 Ferré S. Mechanisms of the psychostimulant effects of caffeine: Implications for substance use disorders. Psychopharmacology (Springer, Berlin) 2016; 233: 1963-1979
- 31 Ferré S. An update on the mechanisms of the psychostimulant effects of caffeine. Journal of Neurochemistry 2008; 105: 1067-1079
- 32 Fisone G, Borgkvist A, Usiello A. Caffeine as a psychomotor stimulant: Mechanisms of action. Cellular and Molecular Life Sciences 2004; 67: 857-872
- 33 Nehlig A, Daval J, Debry G. Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Research Reviews 1992; 17: 139-170
- 34 MKF DS, Gavioli EC, Rosa LS. et al. Craving espresso: The dialetics in classifying caffeine as an abuse drug. Naunyn-Schmiedebergs Archives of Pharmacology 2018; 391: 1301-1318
- 35 McLellan TM, Caldwell JA, Lieberman HR. A review of caffeine’s effects on cognitive, physical and occupational performance. Neuroscience & Biobehavioral Reviews 2016; 71: 294-312
- 36 Pettenuzzo L, Noschang C, von Pozer Toigo E. et al. Effects of chronic administration of caffeine and stress on feeding behavior of rats. Physiology & Behavior 2008; 95: 295-301
- 37 Dunwiddie T, Mansino S. The role and regulation of adenosine in the central nervous system. Ann Rev Neurosci 2001 24. 31-55
- 38 Borea P, Gessi S, Merighi S. et al. Pharmacology of Adenosine Receptors: The State of the Art. Physiological Reviews 2018; 98: 1591-1625
- 39 Calovi S, Mut-Arbona P, Sperlágh B. Microglia and the Purinergic Signaling System. Journal of Neuroscience 2019; 405: 137-147
- 40 Rodriques R, Marques J, Cunha R. Purinergic signalling and brain development. Semin Cell Dev Biol 2018 Dec 4 pii: S1084-9521(18)30065-X. DOI: 10.1016/j.semcdb.2018.12.001. [Epup ahead of print]
- 41 Reiss A, Grossfeld D, Kasselman L. et al. Adenosine and the Cariovascular System. Am J Cardiovasc Drugs 2019 Apr 10 doi: 10.1007/s40256-019-00345-5. [Epub ahead of print].
- 42 Caruso M, Alamo A, Crisafulli E. et al. Adenosine signaling pathways as potential therapeutic targets in respiratory disease. Expert Opinion on Therapeutic Targets 2013; 17: 761-772
- 43 Antanioli L, Fornai M, Blandizzi C. et al. Adenosine signaling and the immune system: When a lot could be too much. Immunology Letters 2019; 205: 9-15
- 44 Alles S, Smith P. Etiology and Pharmacology of Neuropathic Pain. Pharmacological Research 2018; 70: 315-347
- 45 Swnyok J. Adenosine receptor targets for pain. Journal of Neuroscience 2016; 338: 1-18
- 46 Cohen S, Fishman P. Targeting teh A3 adenosine receptor to treat cytokine release syndrom in cancer immunotherapy. Drug Design Development Therapy 2019; 13: 491-497
- 47 Vijayan D, Young A, Teng M. et al. Targeting immunosuppressive adenosine in cancer. Nature Reviews Cancer 2017; 17: 709-724
- 48 Huang Z, Zhang Z, Qu W. Roles of adenosine and its receptors in sleep-wake regulation. Int Rev Neurobiol. 2014 110. 119: 349–71.
- 49 Oertel W, Schulz J. Current and experimental treatments of Parkinson disease: A guide for neuroscientists. Journal Neurochemistry 2016; 139 (Suppl 1): 325-337
- 50 Dinh W, Albrecht-Küpper B, Gheorghiade M. et al. Partial Adenosine A1 Agonist in Heart Failure. Handb Exp Pharmacol 2017 243:. 177-203
- 51 Bahreyni A, Samani S, Khazaei M. et al. Therapeutic potentials of adenosine receptors agonists and antagonists in colitis, current status, and perspectives. Journal of Cellular Physiology 2018; 233: 2733-2740
- 52 Cunha R, Ferré S, Vaugeois J. et al. Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Current Pharmaceutical Design 2008; 14: 1512-1524
- 53 Chen J, Eltzschig H, Fredholm B. Adenosine receptors as drug targets–What are the challanges. Nature Reviews Drug Discovery 2013; 12: 265-286
- 54 Jacobson K, Tosh D, Jain S. et al. Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development. Frontiers in Cellular Neuroscience 2019; 13: 124
- 55 Fredholm B, Abbracchio M. Towards a revised nomenclature for P1 and P2 receptors. Trends in Pharmacological Sciences 1997; 18: 79-82
- 56 Stockwell J, Jakova E, Cayabyab F. Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration. Molecules 2017; 22: pii: E676
- 57 Fredholm BB, Arslan G, Halldner L. et al. Structure and function of adenosine receptors and their genes. Naunyn-Schmiedebergs Archives of Pharmacology 2000; 362: 364-374
- 58 BB F, IJ AP, Jacobson KA. et al. Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacological Revies 2001; 53: 527-552
- 59 Solinas M, Ferre S, Antoniou K. et al. Involvement of adenosine A1 receptors in the discriminative-stimulus effects of caffeine in rats. Psychopharmacology (Springer, Berlin) 2005; 179: 576-586
- 60 Yu L, Coelho JE, Zhang X. et al. Uncovering multiple molecular targets for caffeine using a drug target validation strategy combining A 2A receptor knockout mice with microarray profiling. Physiological Genomics 2009; 37: 199-210
- 61 Daly JW, Shi D, Nikodijevic O. et al. The role of adenosine receptors in the central action of caffeine. Pharmacopsychoecologia 1994; 7: 201-213
- 62 Willson C. The clinical toxicology of caffeine: A review and case study. Toxicology Reports 2018; 5: 1140-1152
- 63 Ferré S, von Euler G, Johansson B. et al. Stimulation of high-afinity adenosine A2 receptors decreases the affinity of dopamine Dr receptors in rat striatal membraned. Proceedings of National Academy of Sciences of the U S A 1991; 88: 7238-7241
- 64 Schiffmann S, Jacobs O, Vanderhaeghen J. Striatal restricted adenosine A2 receptors (RDC8) is expresed by enkephaline but not substance P neurons: An in situ hybridization histochemistry study. Journal of Neurochemistry 1991; 57: 1062-1067
- 65 Bonaventura J, Navarro G, Casadó-Anguera V. et al. Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer. PNAS U S A 2015; 112: E3609 - 3618
- 66 Ferré S, O´Connor W, Fuxe K. et al. The striatopallidal neuron: A main focus for adenosine-dopamine interactions in teh brain. Journal of Neurosciences 1993; 13: 5402-5406
- 67 Azdad K, Gall D, Woods A. et al. Dopamine D2 and adenosine A2A receptors regulate NMDA-mediated excitation in accumbens neurons through A2A-D2 receptor heteromerization. Neuropsychopharmacology. 2009 Mar; 34(4):972–86.
- 68 Ferré S, Bonaventura J, Tomasi D. et al. Allosteric mechanisms within the adenosine A(2A)-domapine D(2) receptor heterotetramer. Neuropsychopharmacology 2015; 104: 154-160
- 69 Navarro G, Aguinaga D, Moreno E. et al. Intracellular calcium levels determine dfferential modulation of allosteric interactions within G protein-coupled receptor heteromers. Chemistry Biology 2014; 21: 1546-1556
- 70 Ferré S. The GPCR heterotetramer: Challenging classical pharmacology. Trends in Pharmacological Sciences 2015; 36: 145-152
- 71 Quarta D, Borycz J, Solinas M. et al. Adenosine receptor-mediated modulation of dopamine release in the nucleus accumbend depends on glutamate neurotransmission and N-methyl-D-aspartate receptor stimulation. J Neurochem 2004; Nov;. 91 (04) : 873–80
- 72 Ciruela F, Casadó V, Rodrigues R. et al. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. Journal Neurosciences 2006; 26: 2080-2087
- 73 Ferré S, Fredholm B, Morelli M. et al. Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends in Neurosciences 1997; 20: 482-487
- 74 Ferré S. An update on the psychostimulant effects of caffeine. Journal Neurochemistry 2008; 105: 1067-1079
- 75 Solinas M, Ferré S, You Z. et al. Caffeine induced dopamine and glutamate release in the shell of the nucleus accumbens. Journal Neurosciences 2002; 22: 6321-6324
- 76 Karcz-Kubicha M, Antoniou K, Terasmaa A. et al. Involvement of adenosine A1 and A2A receptors in the motor effects of caffeine after its acute and chronic administration. Neuropsychopharmacology 2003; 28: 1281-1291
- 77 Borycz J, Pereira M, Melani A. et al. Differential glutamate-dependent and glutamate-independent adenosine A1 receptor-mediated modulation of dopamine release in different striatal compartments. Journal Neurochemistry 2007; 101: 355-363
- 78 Antoniou K, Papadopoulou-Daifoti Z, Hyphantis T. et al. A detailed behavioral analysis of the acute motor effects of caffeine in the rat: Involvement of adenosine A1 und A2A receptors. Psychopharmacology 2005; 183: 280-299
- 79 Quarta D, Ferré S, Solinas M. et al. Opposite modulatory roles for adenosine A1 and A2A receptors on glutamate and dopamine release in the shell of the nucleus accumbens. Effects of chronic caffeine exposure. Journal Neurochemistry 2004; 88: 1151-1158
- 80 Ferré S. Role of the central ascending neurotransmitter systems in the psychostimulant effects of caffeine. Journal of Alzheimer’s Disease 2010; 20 (Suppl 1): S35-S49
- 81 Lazarus M, Chen J, Huang Z. et al. Adenosine and sleep. Handb Exp Pharmacol 2017 Jun 24. doi: 10.1007/164_2017_36. [Epub ahead of print].
- 82 Hines D, Haydon P. Astrocytic adenosine: From synapses to psychiatric disorders. Philosophical Transactions of the Royal Society London B Biology Sciences 2014; 369: 20130594
- 83 Basheer R, Strecker R, Thakkar M. et al. Adenosine and sleep-wake regulation. Progress in Neurobiology 2004; 73: 379-396
- 84 Porkka-Heiskanen T, Strecker R, McCarley R. Brain site-specificity of ectracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: An in vivo microdialysis study. Neuroscience 2000; 99: 505-517
- 85 McCarley R. Neurobiology of REM and NREM sleep. Sleep Medicine 2007; 8: 302-330
- 86 Van Dort C, Baghdoyan H, Lydic R. Adenosine A(1) and A(2A) receptors in mouse prefrontal cortex modulate acetylcholine release and behavioural arousal. Journal Neurosciences 2009; 29: 871-881
- 87 Huang Z, Qu W, Eguchi N. et al. Adenosine A2A, but not A1, receptor mediate the arousal effect of caffeine. Nature Neuroscience 2005; 8: 858-859
- 88 Szymusiak R, McGinty D. Hypothalamic regulation of sleep and arousal. Annals of the NY Acadademy of Sciences 2008; 1129: 275-286
- 89 Lazarus M, Shen H, Cherasse Y. et al. Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. Journal Neurosciences 2011; 31: 10067-10075
- 90 Orrú M, Guitart X, Karcz-Kubicha M. et al. Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans. Neuropharmacology 2013; 67: 476-484
- 91 Carrillo J, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clinical Pharmacokinetics 2000; 39: 127-153
- 92 Sawynok J, Yaksh T. Caffeine as an analgesic: A review of pharmacology and mechanisms of action. Pharmacological Reviews 1993; 45: 43-85
- 93 Porta M, Zima AV, Nani A. et al. Single ryanodine receptor channel basis of caffeine’s action on Ca2+ sparks. Biophys J 2011; Feb. 16 100 (4): 931-938
- 94 Zulli A, RM S, Kubatka P. et al. Caffeine and cardiovascular diseases: Critical review of current research. Eur J Nutr 2016; Jun;. 55 (04) : 1331-1343
- 95 Cockerill SL, Mitcheson JS. Direct block of human ether-a-go-go-related gene potassium channels by caffeine. Journal of Pharmacology and Experimental Therapeutics 2006; 316: 860-868
- 96 Zheng J, Zhao W, Xu K. et al. Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose. Eur J Pharmacol Apr 5 800 23-33. DOI: 10.1016/j.ejphar.2017.02.018. Epub 2017 Feb 16.
- 97 Pohanka M, Dobes P. Caffeine inhibits acetlycholinesterase, but not butyrylcholinesterase. International Journal of Molecular Sciences 2013; 14: 9873-1979
- 98 Liquori A, Hughes J, Grass J. Absorption and subjective effects of caffeine from coffee, cola and capsules. Pharmacolgical Biochemistry Behavior 1997; 58: 721-726
- 99 Arnaud M. Pharmacokinetics and metabolism of natural methylxanthines in animal and man. Handbook of Experimental Pharmacology 2011; 200: 33-91
- 100 White J, Padowski J, Zhong Y. et al. Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy younf adults. Clincal Toxicology 2016; 54: 308-312
- 101 Chvasta E, Cooke A. Absorption and emptying of caffeine from the human stomach. Gastroenterology 1971; 61: 838-843
- 102 Mumford G, Benowitz N, Evans S. et al. Absorption rate of methyxanthines following capsules, cola and chocolate. European Journal of Clinical Pharmacology 1996; 51: 319-325
- 103 Blanchard J, Sawers S. The absolute bioavailability of caffeine in man. European Journal of Clinical Pharmacology 1983; 24: 93-98
- 104 Oestreich-Janzen S. Caffeine: Characterization and properties. Oxford: Academic Press; 2016; doi: HYPERLINK "http://dx.doi.org/10.1016/B978-0-12-384947-2.00098-2" 10.1016/B978-0-12-384947-2.00098-2.
- 105 Kaplan G, Greenblatt D, Ehrenberg B. et al. Dose-dependent pharmacokinetics and psychomotor effects of caffeine in humans. Journal Clinical Psychopharmacology 1997; 37: 693-703
- 106 Bonati M, Latini R, Galletti F. et al. Caffeine disposition after oral doses. Clincal Pharmacolology Theraphy 1982; 32: 98-106
- 107 Mandel H. Update on Caffeine consumption, disposition and action. Food and Chemistry Toxicology 2002; 40: 1231-1234
- 108 Callaban M, Robertson R, Arnaud M. et al. Drug metabolism of [1-methyl-14C]- and [2-14C]caffeine after oral administraton. Drug Metabolism and Disposition 1982; 10: 417-423
- 109 Newton R, Broughton L, Lind M. et al. Plasma and salivary pharmacokinetics of caffeine in man. European Journal of Clinical Pharmacology 1981; 21: 45-52
- 110 Kalow W, Tang B. Use of caffeine metabolite ratio to explore CYP 1A2 and xanthine oxidase activities. Clinical Pharmacology Toxicology 1991; 50: 508-519
- 111 Faber M, Jetter A, Fuhr U. Assessment of CYP1A2 activity in clinical practice: Why, how, and when?. Basic Clinical Pharmacology Toxicology 2005; 97: 125-134
- 112 Rasmussen BB, Brix TH, Kyvik KO. et al. The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenetics 2002; 12: 473-478
- 113 Ferré S, Diaz-Rios M, Salamone JD. et al. New Developments on the Adenosine Mechanisms of the Central Effects of Caffeine and Their Implications for Neuropsychiatric Disorders. Journal of Caffeine and Adenosine Research 2018; 8: 121-131
- 114 Lorist M, Snel J. Caffeine, sleep and quality of life. In: Verster J, Pandi-Permal S, Steiner D. eds. Sleep and quality of life in clinical medicine. New York, U.S.: Human Press, Springer; 2008: 325-332
- 115 Nehlig A. Is caffeine a cognitive enhancer?. Journal of Alzheimer’s Disease 2010; 20 (Suppl 1): S85-94
- 116 Lorist M, Snel J, Kok A. Influence of caffeine on information processing stages in well rested and fatigued subjects. Psychopharmacology 1994; 113: 411-421
- 117 Liebermann H, Tharion W, Shukitt-Hale B. et al. Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land. Psychopharmacology 2002; 164: 250-261
- 118 Einother S, Giesbrecht T. Caffeine as an attention anhancer: Reviewing existing assumptions. Psychopharmacology (Springer, Berlin) 2013; 225: 251-274
- 119 Kosslyn M, Smith E. Higher cognitive functions - introduction. In: Gassaniga M ed, The new cognitive neuroscience. Cambridge, U.K.: The MIT Press; 2001: 961-964
- 120 Renda G, Committeri G, Zimarino M. et al. Genetic determinants of cognitive response to caffeine drinking identified from a double-blind, randomized, controlled trial. European Neuropsychopharmacology 2015; 25: 798-807
- 121 Diamond D. Cognitive, endocrine and mechanistic perspectives on non-linear relationships between arousal and brain function. Nonlinearity in Biology, Toxicology, Medicine 2005; 3: 1-7
- 122 Wood S, Sage J, Shuman T. et al. Psychostimulants and cognition: A continuum of behavioral and cognitive activation. Pharmacological Reviews 2014; 16: 193-221
- 123 Harrell P, Juliano L. Caffeine expectancies influence the subjective and behavioral effects of caffeine. Psychopharmacology (Springer, Berlin) 2009; 207: 335-342
- 124 Anderson K. Impulsivity, caffeine, and task difficulty: A within subjects test of teh Yerkes-Dodson law. Personality and Individual Differences 1994; 16: 813-829
- 125 Diamond D, Campbell A, Park C. et al. The temporal dynamics model of emotional memory processing: A synthesis on the neurobiological basis of stress-induced amnesia, flshbulb and traumatic memories, and the Yerkes-Dodson Law. Neural Plasticity 2007; 207: 60803
- 126 Yerkes R, Dodson J. The relation of strength of stimulus to rapidity of habit-formation. Journal of Comparative Neurology Psychology 1908; 18: 459-482
- 127 Watters P, Martin F, Schreter Z. Caffeine and cognitive performance: The non-linear Yerkes-Dodson law. Human Psychopharmacology 1997; 12: 249-257
- 128 Stafford L, Rusted J, Yeomans M. Caffeine, mood, and performance. A selective review. In: Smith B. Gupta U. Gupta B. eds. Caffeine and activation theory: Effects on health and behavior. Boca Raton: Taylor and Francis; 2007: 284-310
- 129 Harvanko A, Derbyshire K, Schreiber L. et al. The effect of self-regulated caffeine use on cognition in young adults. Human Psychopharmacology 2015; 30: 123-130
- 130 Wesensten N, Belenky G, Kautz M. et al. Maintaining alertness and performance during sleep deprivation: Modafinil versus caffeine. Psychopharmacology 2002; 159: 238-247
- 131 Carvey C, Thompson L, Liebermann H. Caffeine: Mechanisms of action, genetics and behavioral studies conducted in simulators and the field. In: Wesenstein N. ed. Sleep depreivation, stimulant medication, and cognition. Cambridge: Cambridge University Press; 2012: 93-107
- 132 Penetar D, McCann U, Thorne D. et al. Caffeine reversal of sleep depreivation effects on alertness and mood. Psychopharmacology 1993; 112: 359-365
- 133 Lieberman AP, Wurtmann R, Emde G. et al. The effects of low doses of caffeine on human performance and mood. Psychopharmacology 1987; 92: 308-312
- 134 Reyner L, Horne J. Suppression of sleepiness in drivers: Combination of caffeine with a short nap. Psychophysiology 1997; 34: 721-725
- 135 Reyner L, Horne J. Early morning driver sleepiness: Effectiveness of 200 mg caffeine. Psychophysiology 2000; 37: 251-256
- 136 Lieberman H, Wurtman R, Emde G. et al. The effects of caffeine and aspirin an mood and performance. Journal of Clincal Psychopharmacology 1987; 7: 315-320
- 137 Maridakis V, Hering M, O’Connor P. Sensitivity to change in cognitive performance and mood measure of energy and fatigue in response to differing doses of caffeine or breakfast. International Journal of Neurosciences 2009; 119: 975-994
- 138 Maridakis V, O’Connor P, Tomorowski P. Sensitivity to change in cognitive performance and mood measures of energy in fatigue in response to morning cafeine aloneor in combination with carbohydrate. International Journal of Neurosciences 2009; 119: 1239-1258
- 139 Hameleers P, Van Boxtel M, Hogervorst E. et al. Habitual caffeine comsumption and ist relation to memory, attention, planning capacit and psychomotor performance across multiple age groups. Human Psychopharmacolology 2000; 15: 573-581
- 140 Killgore W, Kahn-Greene E, Grugle N. et al. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 2009; 32: 205-216
- 141 Killgore W, Kamimori G, Balkin T. Caffeine improves the efficiency of planning and sequencing abilities during sleep deprivation. Journal of Clinical Psychopharmacology 2014; 34: 660-662
- 142 Soar K, Chapman E, Lavan N. et al. Investigating the effects of caffeine on executive functions using traditional Stroop and a new ecologicall-valid cirtual reality task, the Jansari assessment of Executive Functions (JEF(©)). Appetite 2016; 105: 156-163
- 143 Rivers W, Weber H. The action of caffeine on the capacity for muscular work. The Journal of Physiology 1907; 36: 33-47
- 144 Pickering C. Caffeine and Exercise: What Next?. Sports Med 2019 Jul; 49(7): 1007–1030.[Epup ahead of print].
- 145 Southward K, Rutherfurd-Markwick K, Ali A. The Effect of Acute Caffeine Ingstion on Endurance Performance: A Systematic Review andd Meta-Analysis. Sport Medicine 2018; 48: 1913-1928
- 146 Grgic J, Trexler E, Lazinica B. et al. Effects of caffeine intake on muscle strengths and power: A systematic review and meta-analysis. Journal of the International Society of Sports Nutrition 2018; 15: 11
- 147 Green M, Martin T, Corona B. Effect of Caffeine Supplementation on Quadriceps Performance After Eccentric Exercise. Journal of Strength & Condition Research 2018; 32: 2863-2871
- 148 Grgic J, Pickering C. The effects of caffeine ingestion on isokinetic muscular strength: A meta-analysis. Journal of Science and Medicine in Sport 2019; 22: 353-360
- 149 Lopes-Silva J, Choo H, Franchini E. et al. Isolated ingestion of caffeine and sodium bicarbonate on repeated sprint performance: A systematic review and meta-analysis. J Sci Med Sport 2019; Aug; 22 (08) : 962-972. DOI: 10.1016/j.jsams.2019.03.007. Epub 2019 Mar 20. [Epub aheasd of print].
- 150 Chia J, Barrett L, Chow J. et al. Effects of Caffeine Supplementation on Performance in Ball Games. Sports Medicine 2017; 47: 2453-2471
- 151 Salinero J, Lara B, Del Coso J. Effects of acute ingestion of caffeine on team sports performance: A systematic review an meta-analysis. Research in Sports Medine 2019; 27: 238-256
- 152 Shabir A, Hooton A, Tallis J. et al. The Influence of Caffeine Expectancies on Sport, Exercise, and Cognitive Performance. Nutrients 2018; 2018: Oct 17 10(10). pii:. E1528
- 153 Evans S, Griffiths R. Caffeine tolerance and choice in humans. Psychopharmacology (Springer, Berlin) 1992; 108: 51-59
- 154 Ullrich S, de Vries Y, Kühn S. et al. Feeling smart: Effects of caffeine and glucose on cognition, mood and self-judgement. Physiological Behavior 2015; 151: 629-637
- 155 Olson C, Thronton J, Adam G. et al. Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood. Journal of Clincal Psychopharmacology 2010; 30: 573-578
- 156 Temple J, Ziegler A, Martin C. et al. Subjective Responses to Caffeine Are Influenced by Caffeine Dose, Sex, and Pubertal Stage. Journal of Caffeine Research 2015; 5: 167-175
- 157 Duncan M, Oxford S. The effect of caffeine ingestion on mood state and bench press performance to failure. J Strength Cond Res 2011; Jan;. 25 (01) : 178–85.
- 158 Temple J, Dewey A, Briatico L. Effects of acute caffeine administration on adolescents. Experimental and Clinical Psychopharmacology 2010; 18: 510-520
- 159 Ágoston C, Urbán R, Király O. et al. Why Do You Drink Caffeine? The Developnent of the Motives for Caffeine Consumption Questionnaire (MCCQ) and Its Relationship with Gender, Age and the Types of Caffeinated Beverages. International Journal of Mental Health and Addiction 2018; 16: 981-999
- 160 Temple J, Ziegler A, Graczyk A. et al. Influence of caffeine on the liking of novel-flavored soda in adolescents. Psychopharmacology (Springer, Berlin) 2012; 223: 37-45
- 161 Poole R, Kennedy O, Roderick P. et al. Coffee consumption and health: Umbrella review of meta-analysies of multiple health outcomes. BMJ 2017; 359: j5024
- 162 Jeszka-Skowron M, Zgola-Grzekowiak A, Grzekowiak T. Analytical methods applied for the characterization and the determination of bioactive compounds in coffee. European Food Research Technology 2015; 240: 19-31
- 163 McCreedy A, Bird S, Brown L. et al. Effects of maternal caffeine consumption on the breastfed child: A systematic review. Swiss Medical Weekly 2018; 148: w14665
- 164 Del-Ponte B, Santos I, Tovo-Rodrigues L. et al. Caffeine consumption during pregnancy and ADHD at the age of 11 years: A birth control study. BMJ Open 2016; 6: e012749
- 165 Ogawa N, Ueki H. Secondary mania caused by caffeine. General Hospital Psychiatry 2003; 25: 138-139
- 166 Krankl J, Gitlin M. Caffeine-induced mania in a patient with caffeine use disorder: A case report. The American Journal on Addictions 2015; 24: 289-291
- 167 Verbeeck R. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. European Journal of Clinical Pharmacology 2008; 64: 1147-1161
- 168 Tarka SJ. The toxicology of cocoa and methylxanthines: A review of the literature. Critical Reviews in Toxicology 1982; 9: 275-312
- 169 Wikoff D, Welsh B, Henderson R. et al. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food Chemistry Toxicology 2017; 109 (Pt 1): 585-648
- 170 Doepker C, Lieberman HR, Smith AP. et al. Caffeine: Friend or Foe?. Annual Review of Food Science Technology 2016; 7: 117-137
- 171 Cappelletti S, Piacentino D, Fineschi V. et al. Caffeine-Related Deaths: Manner of Deaths and Categories at Risk. Nutrients 2018; 10 (05) : pii:E611
- 172 Wolter J, Grün D, Otto S. Severe caffein poisoning with rhabdomyolysis. Anaesthesist 2018; 67: 270-274
- 173 Riku S, Yamamoto T, Kubota Y. et al. Refractory ventricular fibrillation caused by caffeine intoxication. Journal of Cardiology Cases 2018; 18: 210-2012
- 174 Magdalan J, Zawadzki M, Skowronek R. et al. Nonfatal and fatal intoxications with pure caffeine - report of three different cases. Forensic Science Medicine Pathology 2017; 13: 355-358
- 175 Andrade A, Sousa C, Pedro M. et al. Dangerous mistake: An accidental caffeine overdose. BMJ Case Rep Jun 8; 2018; pii:bcr-2018-224185
- 176 Wrenn K, Oschner I. Rhabdomyolysis induced by a caffeine overdose. Annals of Ermergency Medicine 1989; 18: 94-97
- 177 Rudolph T, Knudsen K. A case of fatal caffeine poisoning. Acta Anaesthesiologica Scandinavia 2010; 54: 521-523
- 178 Jones W. Review of caffeine-related fatalities along with postmortem blood concentrations in 51 poisoning deaths. Journal of Analytical Toxicology 2017; 41: 167-172
- 179 Kerrigan S, Lindsey T. Fatal caffeine overdose: Two case reports. Forensic Sciences International 2005; 153: 67-69
- 180 Temple J, Bernard C, Lipshultz S. et al. The Safety if Ingested Caffeine: A Comprehensive Review. Frontiers in Psychiatry 2017; 8: 80
- 181 Budney AJ, Brown PC, Griffiths RR. et al. Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals. J Caffeine Res 2013; Jun;. 3 (02) : 67-71
- 182 Strain EC, Mumford GK, Silverman K. et al. Caffeine dependence syndrome. Evidence from case histories and experimental evaluations. JAMA 1994; 272: 1043-1048
- 183 APA. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition (DSM-5). 2013. Publisher: American Psychiatric Association; Place/Location: Washington.
- 184 Griffiths R, Evans S, Heishman S. et al. Low-dose caffeine physical dependence in humans. Journal of Pharmacology and Expimental Therapeutics 1990; 255: 1123-1132
- 185 Silverman K, Evans S, Strain E. et al. Withdrawal syndrome after the double-blind cessation of caffeine consumption. New England Journal of Medicine 1992; 327: 1109-1114
- 186 Juliano L, Griffiths R. A critical review of caffeine withdrawal: Empirical calidation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Springer, Berlin) 2004; 176: 1-29
- 187 Bernstein GA, Carroll ME, Thuras PD. et al. Caffeine dependence in teenagers. Drug and Alcohol Dependence 2002; 66: 1-6
- 188 Oberstar JV, Bernstein GA, Thuras PD. Caffeine use and dependence in adolescents: One-year follow-up. Journal of Child Adolescent Psychopharmacology 2002; 12: 127-135
- 189 Meredith SE, Juliano LM, Hughes JR. et al. Caffeine Use Disorder: A Comprehensive Review and Research Agenda. Journal of Caffeine Research 2013; 3: 114-130
- 190 Juliano L, Evatt D, Richards B. et al. Characteristics of individuals seeking for treatment for caffeine dependence. Psychology of Addictive Behaviors 2012; 26: 948-954
- 191 De Luca M, Bassareo V, Bauer A. et al. Caffeine and accumbens shell dopamine. Journal of Neurochemistry 2007; 103: 157-163
- 192 Acquas E, Tanda G, Di C. Differential effects of caffeine on dopamine and acetylcholine transmission in brain areas of drug-naive and caffeine-pretreated rats. Neuropsychopharmacology 2002; 27: 182-193
- 193 Volkow N, Wang G, Logan J. et al. Caffeine increase striatal dopamine D2 / D3 receptor availability in the human brain. Translational Psychiatry 2015; 5: e549
- 194 Budney AJ, Lee DC, Juliano LM. Evaluating the Validity of Caffeine Use Disorder. Current Psychiatry Reports 2015; 17: 74
- 195 Addicott MA. Caffeine Use Disorder: A Review of the Evidence and Future Implications. Current Addiction Reports 2014; 1: 186-192