Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid, and is chemically related to the adenine and guaninebases 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,[15] and helps to protect them against herbivores and from competition by preventing the germination of nearby seeds,[16] as well as encouraging consumption by select animals such as honey bees.[17] 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.[18] Caffeine is the world's most widely consumed psychoactive drug.[19][20] 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.
Caffeine has both positive and negative health effects. It can treat and prevent the premature infant breathing disorders bronchopulmonary dysplasia of prematurity and apnea of prematurity. Caffeine citrate is on the WHO Model List of Essential Medicines.[21] It may confer a modest protective effect against some diseases,[22] including Parkinson's disease.[23] Some people experience sleep disruption or anxiety if they consume caffeine,[24] but others show little disturbance. Evidence of a risk during pregnancy is equivocal; some authorities recommend that pregnant women limit caffeine to the equivalent of two cups of coffee per day or less.[25][26] Caffeine can produce a mild form of drug dependence – associated with withdrawal symptoms such as sleepiness, headache, and irritability – when an individual stops using caffeine after repeated daily intake.[27][28][2]Tolerance to the autonomic effects of increased blood pressure and heart rate, and increased urine output, develops with chronic use (i.e., these symptoms become less pronounced or do not occur following consistent use).[29]
Caffeine is classified by the US Food and Drug Administration as generally recognized as safe. Toxic doses, over 10 grams per day for an adult, are much higher than the typical dose of under 500 milligrams per day.[30] The European Food Safety Authority reported that up to 400 mg of caffeine per day (around 5.7 mg/kg of body mass per day) does not raise safety concerns for non-pregnant adults, while intakes up to 200 mg per day for pregnant and lactating women do not raise safety concerns for the fetus or the breast-fed infants.[31] A cup of coffee contains 80–175 mg of caffeine, depending on what "bean" (seed) is used, how it is roasted, and how it is prepared (e.g., drip, percolation, or espresso).[32] Thus it requires roughly 50–100 ordinary cups of coffee to reach the toxic dose. However, pure powdered caffeine, which is available as a dietary supplement, can be lethal in tablespoon-sized amounts.
^"Caffeine". ChemSpider. Archived from the original on 14 May 2019. Retrieved 16 November 2021.
^ abcJuliano 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. PMID15448977. S2CID5572188. 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.
^Cite error: The named reference pmid24761279 was invoked but never defined (see the help page).
^ abcPoleszak E, Szopa A, Wyska E, Kukuła-Koch W, Serefko A, Wośko S, et al. (February 2016). "Caffeine augments the antidepressant-like activity of mianserin and agomelatine in forced swim and tail suspension tests in mice". Pharmacological Reports. 68 (1): 56–61. doi:10.1016/j.pharep.2015.06.138. PMID26721352. S2CID19471083.
^ abcdefghi"Caffeine". DrugBank. University of Alberta. 16 September 2013. Archived from the original on 4 May 2015. Retrieved 8 August 2014.
^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.
^"Caffeine". Pubchem Compound. NCBI. Retrieved 16 October 2014. Boiling Point 178 °C (sublimes) Melting Point 238 DEG C (ANHYD)
^"Caffeine". ChemSpider. Royal Society of Chemistry. Archived from the original on 14 May 2019. Retrieved 16 October 2014. Experimental Melting Point: 234–236 °C Alfa Aesar 237 °C Oxford University Chemical Safety Data 238 °C LKT Labs [C0221] 237 °C Jean-Claude Bradley Open Melting Point Dataset 14937 238 °C Jean-Claude Bradley Open Melting Point Dataset 17008, 17229, 22105, 27892, 27893, 27894, 27895 235.25 °C Jean-Claude Bradley Open Melting Point Dataset 27892, 27893, 27894, 27895 236 °C Jean-Claude Bradley Open Melting Point Dataset 27892, 27893, 27894, 27895 235 °C Jean-Claude Bradley Open Melting Point Dataset 6603 234–236 °C Alfa Aesar A10431, 39214 Experimental Boiling Point: 178 °C (Sublimes) Alfa Aesar 178 °C (Sublimes) Alfa Aesar 39214
^Nehlig A, Daval JL, Debry G (1992). "Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects". Brain Research. Brain Research Reviews. 17 (2): 139–170. doi:10.1016/0165-0173(92)90012-B. PMID1356551. S2CID14277779.
^Qi H, Li S (April 2014). "Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson's disease". Geriatrics & Gerontology International. 14 (2): 430–9. doi:10.1111/ggi.12123. PMID23879665. S2CID42527557.
^American College of Obstetricians and Gynecologists (August 2010). "ACOG CommitteeOpinion No. 462: Moderate caffeine consumption during pregnancy". Obstetrics and Gynecology. 116 (2 Pt 1): 467–8. doi:10.1097/AOG.0b013e3181eeb2a1. PMID20664420.
^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 375. ISBN978-0-07-148127-4. Long-term caffeine use can lead to mild physical dependence. A withdrawal syndrome characterized by drowsiness, irritability, and headache typically lasts no longer than a day. True compulsive use of caffeine has not been documented.
^American Psychiatric Association (2013). "Substance-Related and Addictive Disorders"(PDF). American Psychiatric Publishing. pp. 1–2. Archived from the original(PDF) on 1 July 2014. Retrieved 10 July 2015. Substance use disorder in DSM-5 combines the DSM-IV categories of substance abuse and substance dependence into a single disorder measured on a continuum from mild to severe. ... Additionally, the diagnosis of dependence caused much confusion. Most people link dependence with "addiction" when in fact dependence can be a normal body response to a substance. ... DSM-5 will not include caffeine use disorder, although research shows that as little as two to three cups of coffee can trigger a withdrawal effect marked by tiredness or sleepiness. There is sufficient evidence to support this as a condition, however it is not yet clear to what extent it is a clinically significant disorder.