Nestler EJ, Hymen SE, Holtzmann DM, Malenka RC. "16". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3rded.). McGraw-Hill Education. True compulsive use of caffeine has not been documented, and, consequently, these drugs are not considered addictive. 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.

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Institute of Medicine (US) Committee on Military Nutrition Research (2001). "2, Pharmacology of Caffeine". Pharmacology of Caffeine. National Academies Press (US). Archived from the original on 28 September 2021 . Retrieved 15 December 2022. In addition to its activity at adenosine receptors, caffeine is an inositol trisphosphate receptor 1 antagonist and a voltage-independent activator of the ryanodine receptors ( RYR1, RYR2, and RYR3). [167] It is also a competitive antagonist of the ionotropic glycine receptor. [168] Effects on striatal dopamine Caffeine was formerly used as a second-line treatment for ADHD. It is considered less effective than methylphenidate or amphetamine but more so than placebo for children with ADHD. [49] [50] Children, adolescents, and adults with ADHD are more likely to consume caffeine, perhaps as a form of self-medication. [50] [51] Enhancing performance Cognitive performance 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.In healthy children, moderate caffeine intake under 400mg produces effects that are "modest and typically innocuous". [74] [75] As early as six months old, infants can metabolize caffeine at the same rate as that of adults. [76] Higher doses of caffeine (>400mg) can cause physiological, psychological and behavioral harm, particularly for children with psychiatric or cardiac conditions. [74] There is no evidence that coffee stunts a child's growth. [77] The American Academy of Pediatrics recommends that caffeine consumption is not appropriate for children and adolescents and should be avoided. [78] This recommendation is based on a clinical report released by American Academy of Pediatrics in 2011 with a review of 45 publications from 1994 to 2011 and includes inputs from various stakeholders (Pediatricians, Committee on nutrition, Canadian Pediatric Society, Centers for Disease Control & Prevention, Food and Drug Administration, Sports Medicine & Fitness committee, National Federations of High School Associations). [78] For children age 12 and under, Health Canada recommends a maximum daily caffeine intake of no more than 2.5 milligrams per kilogram of body weight. Based on average body weights of children, this translates to the following age-based intake limits: [72] Age range O'Connor A (4 March 2008). "Really? The claim: caffeine causes dehydration". New York Times. Archived from the original on 3 September 2011 . Retrieved 3 August 2009. In general, dark-roast coffee has very slightly less caffeine than lighter roasts because the roasting process reduces caffeine content of the bean by a small amount. [229] [230] Tea a b Murray A, Traylor J (January 2019). "Caffeine Toxicity". StatPearls [Internet] (Mini-review). PMID 30422505. Until recently, the Seventh-day Adventist Church asked for its members to "abstain from caffeinated drinks", but has removed this from baptismal vows (while still recommending abstention as policy). [282] Some from these religions believe that one is not supposed to consume a non-medical, psychoactive substance, or believe that one is not supposed to consume a substance that is addictive. The Church of Jesus Christ of Latter-day Saints has said the following with regard to caffeinated beverages: "... the Church revelation spelling out health practices (Doctrine and Covenants 89) does not mention the use of caffeine. The Church's health guidelines prohibit alcoholic drinks, smoking or chewing of tobacco, and 'hot drinks' – taught by Church leaders to refer specifically to tea and coffee." [283]

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Salerno BB, Knights EK (2010). Pharmacology for health professionals (3rded.). Chatswood, N.S.W.: Elsevier Australia. p.433. ISBN 978-0-7295-3929-6. In contrast to the amphetamines, caffeine does not cause euphoria, stereotyped behaviors or psychoses. Smith A (September 2002). "Effects of caffeine on human behavior". Food and Chemical Toxicology. 40 (9): 1243–55. doi: 10.1016/S0278-6915(02)00096-0. PMID 12204388. Extraction by organic solvents: Certain organic solvents such as ethyl acetate present much less health and environmental hazard than chlorinated and aromatic organic solvents used formerly. Another method is to use triglyceride oils obtained from spent coffee grounds. [207] Jiang X, Zhang D, Jiang W (February 2014). "Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies". European Journal of Nutrition. 53 (1): 25–38. doi: 10.1007/s00394-013-0603-x. PMID 24150256. S2CID 5566177. Dose-response analysis suggested that incidence of T2DM decreased ...14% [0.86 (0.82-0.91)] for every 200 mg/day increment in caffeine intake.

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Caffeine may be synthesized in the lab starting with dimethylurea and malonic acid. [ clarification needed] [200] [201] [205] Robiquet was one of the first to isolate and describe the properties of pure caffeine, [262] whereas Pelletier was the first to perform an elemental analysis. [263] 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. 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