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Death from caffeine ingestion appears to be rare, and most commonly caused by an intentional overdose of medications. [144] In 2016, 3702 caffeine-related exposures were reported to Poison Control Centers in the United States, of which 846 required treatment at a medical facility, and 16 had a major outcome; and several caffeine-related deaths are reported in case studies. [144] The LD 50 of caffeine in rats is 192 milligrams per kilogram, the fatal dose in humans is estimated to be 150–200 milligrams per kilogram (2.2lb) of body mass (75–100 cups of coffee for a 70kg (150lb) adult). [145] [146] There are cases where doses as low as 57 milligrams per kilogram have been fatal. [147] A number of fatalities have been caused by overdoses of readily available powdered caffeine supplements, for which the estimated lethal amount is less than a tablespoon. [148] The lethal dose is lower in individuals whose ability to metabolize caffeine is impaired due to genetics or chronic liver disease. [149] A death was reported in 2013 of a man with liver cirrhosis who overdosed on caffeinated mints. [150] [151] Interactions a b c Karch SB (2009). Karch's pathology of drug abuse (4thed.). Boca Raton: CRC Press. pp.229–230. ISBN 978-0-8493-7881-2. The suggestion has also been made that a caffeine dependence syndrome exists... In one controlled study, dependence was diagnosed in 16 of 99individuals who were evaluated. The median daily caffeine consumption of this group was only 357mg per day (Strain et al., 1994). Simulated keypress changed from right context menu key to F15 as this is likely to be even less intrusive. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL (November 2001). "Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes". The American Journal of Clinical Nutrition. 74 (5): 694–700. doi: 10.1093/ajcn/74.5.694. PMID 11684540. Caffeine's biological half-life– the time required for the body to eliminate one-half of a dose– varies widely among individuals according to factors such as pregnancy, other drugs, liver enzyme function level (needed for caffeine metabolism) and age. In healthy adults, caffeine's half-life is between 3 and 7hours. [8] The half-life is decreased by 30-50% in adult male smokers, approximately doubled in women taking oral contraceptives, and prolonged in the last trimester of pregnancy. [126] In newborns the half-life can be 80hours or more, dropping very rapidly with age, possibly to less than the adult value by age 6 months. [126] The antidepressant fluvoxamine (Luvox) reduces the clearance of caffeine by more than 90%, and increases its elimination half-life more than tenfold; from 4.9hours to 56hours. [187]
Since this observation was first published, caffeine addiction has been added as an official diagnosis in ICDM9. This decision is disputed by many and is not supported by any convincing body of experimental evidence.... All of these observations strongly suggest that caffeine does not act on the dopaminergic structures related to addiction, nor does it improve performance by alleviating any symptoms of withdrawal Food Standards Agency publishes new caffeine advice for pregnant women". Archived from the original on 17 October 2010 . Retrieved 3 August 2009. activehours:........xxxxxxxx........ - put 24 . or x characters - which indicate from hour 0 to hour 23 of the day. Caffeine will Kuczkowski KM (November 2009). "Caffeine in pregnancy". Archives of Gynecology and Obstetrics. 280 (5): 695–8. doi: 10.1007/s00404-009-0991-6. PMID 19238414. S2CID 6475015.
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Schulteis G (2010). "Brain stimulation and addiction". In Koob GF, Le Moal M, Thompson RF (eds.). Encyclopedia of Behavioral Neuroscience. Elsevier. p.214. ISBN 978-0-08-091455-8. Therefore, caffeine and other adenosine antagonists, while weakly euphoria-like on their own, may potentiate the positive hedonic efficacy of acute drug intoxication and reduce the negative hedonic consequences of drug withdrawal. a b Fintel M, Langer GA, Duenas C (November 1984). "Effects of low sodium perfusion on cardiac caffeine sensitivity and calcium uptake". Journal of Molecular and Cellular Cardiology. 16 (11): 1037–1045. doi: 10.1016/s0022-2828(84)80016-4. PMID 6520875.
While caffeine does not directly bind to any dopamine receptors, it influences the binding activity of dopamine at its receptors in the striatum by binding to adenosine receptors that have formed GPCR heteromers with dopamine receptors, specifically the A 1– D 1 receptor heterodimer (this is a receptor complex with 1 adenosine A 1 receptor and 1 dopamine D 1 receptor) and the A 2A– D 2 receptor heterotetramer (this is a receptor complex with 2 adenosine A 2A receptors and 2 dopamine D 2 receptors). [169] [170] [171] [172] The A 2A–D 2 receptor heterotetramer has been identified as a primary pharmacological target of caffeine, primarily because it mediates some of its psychostimulant effects and its pharmacodynamic interactions with dopaminergic psychostimulants. [170] [171] [172] Chocolate derived from cocoa beans contains a small amount of caffeine. The weak stimulant effect of chocolate may be due to a combination of theobromine and theophylline, as well as caffeine. [237] A typical 28-gram serving of a milk chocolate bar has about as much caffeine as a cup of decaffeinated coffee. By weight, dark chocolate has one to two times the amount of caffeine as coffee: 80–160mg per 100g. Higher percentages of cocoa such as 90% amount to 200mg per 100g approximately and thus, a 100-gram 85% cocoa chocolate bar contains about 195mg caffeine. [221] Tablets No-Doz 100mg caffeine tablets Caffeine can delay or prevent sleep and improves task performance during sleep deprivation. [54] Shift workers who use caffeine make fewer mistakes that could result from drowsiness. [55] Dulloo AG, Geissler CA, Horton T, Collins A, Miller DS (January 1989). "Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers". The American Journal of Clinical Nutrition. 49 (1): 44–50. doi: 10.1093/ajcn/49.1.44. PMID 2912010.
References
a b c Juliano LM, Griffiths RR (October 2004). "A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features". Psychopharmacology. 176 (1): 1–29. doi: 10.1007/s00213-004-2000-x. PMID 15448977. S2CID 5572188. Results: Of 49 symptom categories identified, the following 10 fulfilled validity criteria: headache, fatigue, decreased energy/ activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and foggy/not clearheaded. In addition, flu-like symptoms, nausea/vomiting, and muscle pain/stiffness were judged likely to represent valid symptom categories. In experimental studies, the incidence of headache was 50% and the incidence of clinically significant distress or functional impairment was 13%. Typically, onset of symptoms occurred 12–24 h after abstinence, with peak intensity at 20–51 h, and for a duration of 2–9 days. Kohn R, Keller M (2015). "Chapter 34 Emotions". In Tasman A, Kay J, Lieberman JA, First MB, Riba M (eds.). Psychiatry. Vol.1. New York: John Wiley & Sons. pp.557–558. ISBN 978-1-118-84547-9. Table 34-12... Caffeine Intoxication – Euphoria
Boekema PJ, Samsom M, van Berge Henegouwen GP, Smout AJ (1999). "Coffee and gastrointestinal function: facts and fiction. A review". Scandinavian Journal of Gastroenterology. Supplement. 34 (230): 35–9. doi: 10.1080/003655299750025525. PMID 10499460.
Robertson D, Wade D, Workman R, Woosley RL, Oates JA (April 1981). "Tolerance to the humoral and hemodynamic effects of caffeine in man". The Journal of Clinical Investigation. 67 (4): 1111–7. doi: 10.1172/JCI110124. PMC 370671. PMID 7009653. Decaffeinated" coffees do in fact contain caffeine in many cases– some commercially available decaffeinated coffee products contain considerable levels. One study found that decaffeinated coffee contained 10mg of caffeine per cup, compared to approximately 85mg of caffeine per cup for regular coffee. [208] Detection in body fluids
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