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Ebenezer I (2015). Neuropsychopharmacology and Therapeutics. John Wiley & Sons. p.18. ISBN 978-1-118-38578-4. However, in contrast to other psychoactive stimulants, such as amphetamine and cocaine, caffeine and the other methylxanthines do not produce euphoria, stereotyped behaviors or psychotic like symptoms in large doses. High caffeine consumption in energy drinks (at least 1 liter or 320mg of caffeine) was associated with short-term cardiovascular side effects including hypertension, prolonged QT interval, and heart palpitations. These cardiovascular side effects were not seen with smaller amounts of caffeine consumption in energy drinks (less than 200mg). [79] Severe intoxication Wang L, Shen X, Wu Y, Zhang D (March 2016). "Coffee and caffeine consumption and depression: A meta-analysis of observational studies". The Australian and New Zealand Journal of Psychiatry. 50 (3): 228–42. doi: 10.1177/0004867415603131. PMID 26339067. S2CID 23377304. a b "Caffeine: Summary of Clinical Use". IUPHAR Guide to Pharmacology. The International Union of Basic and Clinical Pharmacology. Archived from the original on 14 February 2015 . Retrieved 13 February 2015.
a b Downs J, Giust J, Dunn DW (September 2017). "Considerations for ADHD in the child with epilepsy and the child with migraine". Expert Review of Neurotherapeutics. 17 (9): 861–869. doi: 10.1080/14737175.2017.1360136. PMID 28749241. S2CID 29659192. Grosso G, Micek A, Castellano S, Pajak A, Galvano F (January 2016). "Coffee, tea, caffeine and risk of depression: A systematic review and dose-response meta-analysis of observational studies". Molecular Nutrition & Food Research. 60 (1): 223–34. doi: 10.1002/mnfr.201500620. PMID 26518745. According to Chinese legend, the Chinese emperor Shennong, reputed to have reigned in about 3000 BCE, inadvertently discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted. [247] Shennong is also mentioned in Lu Yu's Cha Jing, a famous early work on the subject of tea. [248]
Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor. [173] As a competitive nonselective phosphodiesterase inhibitor, [174] caffeine raises intracellular cyclic AMP, activates protein kinase A, inhibits TNF-alpha [175] [176] and leukotriene [177] synthesis, and reduces inflammation and innate immunity. [177] Caffeine also affects the cholinergic system where it is a moderate inhibitor of the enzyme acetylcholinesterase. [178] [179] Pharmacokinetics Caffeine is metabolized in the liver via a single demethylation, resulting in three primary metabolites, paraxanthine (84%), theobromine (12%), and theophylline (4%), depending on which methyl group is removed. Urinary metabolites of caffeine in humans at 48 hours post-dose [180] In 1827, M. Oudry isolated "théine" from tea, [264] but in 1838 it was proved by Mulder [265] and by Carl Jobst [266] that theine was actually the same as caffeine. Gaudiya Vaishnavas generally also abstain from caffeine, because they believe it clouds the mind and overstimulates the senses. [284] To be initiated under a guru, one must have had no caffeine, alcohol, nicotine or other drugs, for at least a year. [285]
Prynne M (11 October 2013). "Warning over caffeine sweets after father dies from overdose". The Telegraph. Archived from the original on 11 October 2013 . Retrieved 13 October 2013. The addition of caffeine (100–130mg) to commonly prescribed pain relievers such as paracetamol or ibuprofen modestly improves the proportion of people who achieve pain relief. [47]
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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] Shen JG, Brooks MB, Cincotta J, Manjourides JD (February 2019). "Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis". Journal of Science and Medicine in Sport. 22 (2): 232–238. doi: 10.1016/j.jsams.2018.07.022. PMID 30170953. Some beverages combine alcohol with caffeine to create a caffeinated alcoholic drink. The stimulant effects of caffeine may mask the depressant effects of alcohol, potentially reducing the user's awareness of their level of intoxication. Such beverages have been the subject of bans due to safety concerns. In particular, the United States Food and Drug Administration has classified caffeine added to malt liquor beverages as an "unsafe food additive". [246] a b "Caffeine (Systemic)". MedlinePlus. 25 May 2000. Archived from the original on 23 February 2007 . Retrieved 3 August 2009.
According to DSST, alcohol causes a decrease in performance on their standardized tests, and caffeine causes a significant improvement. [153] When alcohol and caffeine are consumed jointly, the effects of the caffeine are changed, but the alcohol effects remain the same. [154] For example, consuming additional caffeine does not reduce the effect of alcohol. [154] However, the jitteriness and alertness given by caffeine is decreased when additional alcohol is consumed. [154] Alcohol consumption alone reduces both inhibitory and activational aspects of behavioral control. Caffeine antagonizes the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control. [155] The Dietary Guidelines for Americans recommend avoidance of concomitant consumption of alcohol and caffeine, as taking them together may lead to increased alcohol consumption, with a higher risk of alcohol-associated injury. Tea contains more caffeine than coffee by dry weight. A typical serving, however, contains much less, since less of the product is used as compared to an equivalent serving of coffee. Also contributing to caffeine content are growing conditions, processing techniques, and other variables. Thus, teas contain varying amounts of caffeine. [231] Schmidt B, Anderson PJ, Doyle LW, Dewey D, Grunau RE, Asztalos EV, Davis PG, Tin W, Moddemann D, Solimano A, Ohlsson A, Barrington KJ, Roberts RS (January 2012). "Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity". JAMA. 307 (3): 275–82. doi: 10.1001/jama.2011.2024. PMID 22253394.
Levounis P, Herron AJ (2014). The Addiction Casebook. American Psychiatric Pub. p.49. ISBN 978-1-58562-458-4. O'Callaghan F, Muurlink O, Reid N (7 December 2018). "Effects of caffeine on sleep quality and daytime functioning". Risk Management and Healthcare Policy. 11: 263–271. doi: 10.2147/RMHP.S156404. PMC 6292246. PMID 30573997. Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid, and is chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It is found in the seeds, fruits, nuts, or leaves of a number of plants native to Africa, East Asia and South America, [18] and helps to protect them against herbivores and from competition by preventing the germination of nearby seeds, [19] as well as encouraging consumption by select animals such as honey bees. [20] The best-known source of caffeine is the coffee bean, the seed of the Coffea plant. People may drink beverages containing caffeine to relieve or prevent drowsiness and to improve cognitive performance. To make these drinks, caffeine is extracted by steeping the plant product in water, a process called infusion. Caffeine-containing drinks, such as coffee, tea, and cola, are consumed globally in high volumes. In 2020, almost 10 million tonnes of coffee beans were consumed globally. [21] Caffeine is the world's most widely consumed psychoactive drug. [22] [23] Unlike most other psychoactive substances, caffeine remains largely unregulated and legal in nearly all parts of the world. Caffeine is also an outlier as its use is seen as socially acceptable in most cultures and even encouraged in others. Jamieson RW (2001). "The essence of commodification: caffeine dependencies in the early modern world". Journal of Social History. 35 (2): 269–294. doi: 10.1353/jsh.2001.0125. JSTOR 3790189. PMID 18546583. S2CID 22532559. 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]
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