Treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require peritoneal dialysis , hemodialysis , or hemofiltration. Caffeine is a substrate for CYP1A2 , and interacts with many substances through this and other mechanisms. According to DSST , alcohol provides a reduction in performance and caffeine has a significant improvement in performance. Caffeine antagonizes the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control.
Birth control pills can extend the half-life of caffeine, requiring greater attention to caffeine consumption. Caffeine sometimes increases the effectiveness of some medications, such as those for headaches. The pharmacological effects of adenosine may be blunted in individuals taking large quantities of methylxanthines like caffeine. In the absence of caffeine and when a person is awake and alert, little adenosine is present in CNS neurons.
With a continued wakeful state, over time adenosine accumulates in the neuronal synapse , in turn binding to and activating adenosine receptors found on certain CNS neurons; when activated, these receptors produce a cellular response that ultimately increases drowsiness. When caffeine is consumed, it antagonizes adenosine receptors; in other words, caffeine prevents adenosine from activating the receptor by blocking the location on the receptor where adenosine binds to it. As a result, caffeine temporarily prevents or relieves drowsiness, and thus maintains or restores alertness.
Caffeine is an antagonist at all four adenosine receptor subtypes A 1 , A 2A , A 2B , and A 3 , although with varying potencies. Heart palpitations are caused by blockade of the A 1 receptor. Because caffeine is both water- and lipid-soluble, it readily crosses the blood—brain barrier that separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action is as a nonselective antagonist of adenosine receptors in other words, an agent that reduces the effects of adenosine. The caffeine molecule is structurally similar to adenosine, and is capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive antagonist.
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. 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.
Caffeine also causes the release of dopamine in the dorsal striatum and nucleus accumbens core a substructure within the ventral striatum , but not the nucleus accumbens shell , by antagonizing A 1 receptors in the axon terminal of dopamine neurons and A 1 — A 2A heterodimers a receptor complex composed of 1 adenosine A 1 receptor and 1 adenosine A 2A receptor in the axon terminal of glutamate neurons. Caffeine, like other xanthines , also acts as a phosphodiesterase inhibitor. Caffeine antagonizes adenosine A2A receptors in the ventrolateral preoptic area VLPO , thereby reducing inhibitory GABA neurotransmission to the tuberomammillary nucleus , a histaminergic projection nucleus that activation-dependently promotes arousal.
Caffeine from coffee or other beverages is absorbed by the small intestine within 45 minutes of ingestion and distributed throughout all bodily tissues. Caffeine is metabolized in the liver by the cytochrome P oxidase enzyme system, in particular, by the CYP1A2 isozyme, into three dimethyl xanthines ,  each of which has its own effects on the body:. Caffeine can accumulate in individuals with severe liver disease , increasing its half-life.
A review found that increased caffeine intake was associated with a variation in two genes that increase the rate of caffeine catabolism. The xanthine core of caffeine contains two fused rings, a pyrimidinedione and imidazole. The pyrimidinedione in turn contains two amide functional groups that exist predominantly in a zwitterionic resonance the location from which the nitrogen atoms are double bonded to their adjacent amide carbons atoms.
Hence all six of the atoms within the pyrimidinedione ring system are sp 2 hybridized and planar. The biosynthesis of caffeine is an example of convergent evolution among different species. Caffeine may be synthesized in the lab starting with dimethylurea and malonic acid. Commercial supplies of caffeine are not usually manufactured synthetically because the chemical is readily available as a byproduct of decaffeination.
Extraction of caffeine from coffee, to produce caffeine and decaffeinated coffee, can be performed using a number of solvents. Benzene , chloroform , trichloroethylene , and dichloromethane have all been used over the years but for reasons of safety, environmental impact, cost, and flavor, they have been superseded by the following main methods:. Caffeine can be quantified in blood, plasma, or serum to monitor therapy in neonates, confirm a diagnosis of poisoning, or facilitate a medicolegal death investigation. Some analog substances have been created which mimic caffeine's properties with either function or structure or both.
Of the latter group are the xanthines DMPX  and 8-chlorotheophylline , which is an ingredient in dramamine. Members of a class of nitrogen substituted xanthines are often proposed as potential alternatives to caffeine. Caffeine, as do other alkaloids such as cinchonine , quinine or strychnine , precipitates polyphenols and tannins. This property can be used in a quantitation method. Around sixty plant species are known to contain caffeine.
Other sources include yaupon holly leaves, South American holly yerba mate leaves, seeds from Amazonian maple guarana berries, and Amazonian holly guayusa leaves. Temperate climates around the world have produced unrelated caffeine-containing plants. Caffeine in plants acts as a natural pesticide : it can paralyze and kill predator insects feeding on the plant. Firstly, in the cell vacuoles where it is complexed with polyphenols. This caffeine probably is released into the mouth parts of insects, to discourage herbivory. Secondly, around the vascular bundles, where it probably inhibits pathogenic fungi from entering and colonizing the vascular bundles.
The differing perceptions in the effects of ingesting beverages made from various plants containing caffeine could be explained by the fact that these beverages also contain varying mixtures of other methylxanthine alkaloids , including the cardiac stimulants theophylline and theobromine , and polyphenols that can form insoluble complexes with caffeine. Products containing caffeine are coffee, tea, soft drinks "colas" , energy drinks , other beverages, chocolate ,  caffeine tablets, other oral products, and inhalation products.
The world's primary source of caffeine is the coffee "bean" the seed of the coffee plant , from which coffee is brewed. Caffeine content in coffee varies widely depending on the type of coffee bean and the method of preparation used;  even beans within a given bush can show variations in concentration.
In general, one serving of coffee ranges from 80 to milligrams, for a single shot 30 milliliters of arabica-variety espresso , to approximately — milligrams for a cup milliliters of drip coffee. 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. Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee. Preparation and many other factors have a significant impact on tea, and color is a very poor indicator of caffeine content. Teas like the pale Japanese green tea , gyokuro , for example, contain far more caffeine than much darker teas like lapsang souchong , which has very little.
Caffeine is also a common ingredient of soft drinks , such as cola , originally prepared from kola nuts. Soft drinks typically contain 0 to 55 milligrams of caffeine per 12 ounce serving. The caffeine in these drinks either originates from the ingredients used or is an additive derived from the product of decaffeination or from chemical synthesis. Guarana, a prime ingredient of energy drinks, contains large amounts of caffeine with small amounts of theobromine and theophylline in a naturally occurring slow-release excipient.
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. Tablets offer several advantages over coffee, tea, and other caffeinated beverages, including convenience, known dosage, and avoidance of concomitant intake of sugar, acids, and fluids.
Manufacturers of caffeine tablets claim that using caffeine of pharmaceutical quality improves mental alertness. One U. There are several products being marketed that offer inhalers that deliver proprietary blends of supplements, with caffeine being a key ingredient. According to Chinese legend, the Chinese emperor Shennong , reputed to have reigned in about BCE, inadvertently discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted. The earliest credible evidence of either coffee drinking or knowledge of the coffee plant appears in the middle of the fifteenth century, in the Sufi monasteries of the Yemen in southern Arabia.
From the Middle East, coffee drinking spread to Italy, then to the rest of Europe, and coffee plants were transported by the Dutch to the East Indies and to the Americas. Kola nut use appears to have ancient origins. It is chewed in many West African cultures, in both private and social settings, to restore vitality and ease hunger pangs.
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The earliest evidence of cocoa bean use comes from residue found in an ancient Mayan pot dated to BCE. Also, chocolate was consumed in a bitter and spicy drink called xocolatl , often seasoned with vanilla , chile pepper , and achiote. Xocolatl was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content.
Chocolate was an important luxury good throughout pre-Columbian Mesoamerica , and cocoa beans were often used as currency. Xocolatl was introduced to Europe by the Spaniards , and became a popular beverage by The Spaniards also introduced the cacao tree into the West Indies and the Philippines. It was used in alchemical processes, where it was known as "black bean". The leaves and stems of the yaupon holly Ilex vomitoria were used by Native Americans to brew a tea called asi or the " black drink ". In , the German chemist Friedlieb Ferdinand Runge isolated relatively pure caffeine for the first time; he called it "Kaffebase" i.
Furthermore, Berzelius stated that the French chemists had made their discoveries independently of any knowledge of Runge's or each other's work. Caffeine, noun feminine. Crystallizable substance discovered in coffee in by Mr. Pelletier and Caventou obtained caffeine; but because their research had a different goal and because their research had not been finished, they left priority on this subject to Mr. We do not know why Mr. Robiquet has not published the analysis of coffee which he read to the Pharmacy Society.
Its publication would have allowed us to make caffeine better known and give us accurate ideas of coffee's composition Robiquet was one of the first to isolate and describe the properties of pure caffeine,  whereas Pelletier was the first to perform an elemental analysis. In , M. In , German chemist Hermann Emil Fischer — first synthesized caffeine from its chemical components i. Because it was recognized that coffee contained some compound that acted as a stimulant, first coffee and later also caffeine has sometimes been subject to regulation.
For example, in the 16th century Islamists in Mecca and in the Ottoman Empire made coffee illegal for some classes. In , caffeine became the focus of one of the earliest documented health scares, when the US government seized 40 barrels and 20 kegs of Coca-Cola syrup in Chattanooga, Tennessee , alleging the caffeine in its drink was "injurious to health".
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House of Representatives in to amend the Pure Food and Drug Act , adding caffeine to the list of "habit-forming" and "deleterious" substances, which must be listed on a product's label. However, there is no regulatory provision for mandatory quantitative labeling of caffeine, e. There are a number of food ingredients that naturally contain caffeine.
These ingredients must appear in food ingredient lists. However, as is the case for "food additive caffeine", there is no requirement to identify the quantitative amount of caffeine in composite foods containing ingredients that are natural sources of caffeine. While coffee or chocolate are broadly recognized as caffeine sources, some ingredients e. For these natural sources of caffeine, there is no regulatory provision requiring that a food label identify the presence of caffeine nor state the amount of caffeine present in the food.
The Church of Jesus Christ of Latter-day Saints has said the following with regard to caffeinated beverages: ". 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. Gaudiya Vaishnavas generally also abstain from caffeine, because they believe it clouds the mind and over-stimulates the senses. Caffeinated beverages are widely consumed by Muslims today.
In the 16th century, some Muslim authorities made unsuccessful attempts to ban them as forbidden "intoxicating beverages" under Islamic dietary laws. Recently discovered bacteria Pseudomonas putida CBB5 can live on pure caffeine and can cleave caffeine into carbon dioxide and ammonia. Caffeine is toxic to birds  and to dogs and cats,  and has a pronounced adverse effect on mollusks , various insects, and spiders.
Caffeine has been used to double chromosomes in haploid wheat. Caffeine-induced increases in performance have been observed in aerobic as well as anaerobic sports for reviews, see [26,30,31] From Wikipedia, the free encyclopedia. This article is about the stimulant drug. For other uses, see Caffeine disambiguation. A central nervous system stimulant. IUPAC name. Interactive image. Main article: Caffeine citrate. Main article: Caffeine dependence. See also: Caffeinated alcoholic drink.
Postsynaptic density. Synaptic vesicle. Neurotransmitter transporter. Axon terminal. Synaptic cleft. Main article: Decaffeination. See also: Caffeinated drink. Main articles: History of chocolate , History of coffee , History of tea , and History of yerba mate. See also: Effect of psychoactive drugs on animals. He was right; for soon thereafter I discovered therein caffeine, which became so famous on account of its high nitrogen content.
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. Karch's pathology of drug abuse 4th ed. The suggestion has also been made that a caffeine dependence syndrome exists This decision is disputed by many and is not supported by any convincing body of experimental evidence. American Psychiatric Publishing. Archived from the original PDF on 15 August Retrieved 10 July 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. Abingdon: CRC Press.
Archived from the original PDF on 29 January 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. University of Alberta. Retrieved 8 August Pharmacological Reports. Pubchem Compound. Retrieved 16 October Royal Society of Chemistry. Brain Research. Brain Research Reviews. Meredith Hopes ed. Australian Broadcasting Corporation. Archived from the original on 26 July Retrieved 15 January Encyclopedia of Food and Health.
Elsevier Science. Retrieved 17 June Greenwood Press. Food and Chemical Toxicology.
Caffeine and Activation Theory: Effects on Health and Behavior
World Health Organization. October [April ]. Retrieved 23 December Mayo Clinic. Retrieved 15 April Obstetrics and Gynecology. The Journal of Clinical Investigation. Journal of Food Science. Pediatric Pulmonology. Biology of the Neonate. The New England Journal of Medicine. The Journal of Physiology. Journal of Perinatology. Retrieved 13 February The American Journal of Medicine. Clin Respir J. Orthomolecular Psychiatry.
Journal of Alzheimer's Disease. Caffeine does not usually affect performance in learning and memory tasks, although caffeine may occasionally have facilitatory or inhibitory effects on memory and learning. Caffeine facilitates learning in tasks in which information is presented passively; in tasks in which material is learned intentionally, caffeine has no effect. Caffeine facilitates performance in tasks involving working memory to a limited extent, but hinders performance in tasks that heavily depend on this, and caffeine appears to improve memory performance under suboptimal alertness.
Most studies, however, found improvements in reaction time. The ingestion of caffeine does not seem to affect long-term memory. Its indirect action on arousal, mood and concentration contributes in large part to its cognitive enhancing properties. Progress in Brain Research. Ker K ed. Nutrition Reviews. Quote: Caffeine-induced increases in performance have been observed in aerobic as well as anaerobic sports for reviews, see [26,30,31] Sports Medicine. Primary Care. Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training The American Journal of Clinical Nutrition.
Journal of the International Society of Sports Nutrition. Medicine and Science in Sports and Exercise. European Journal of Sport Science. Journal of Science and Medicine in Sport. Health Canada. March Retrieved 8 November The Addiction Casebook. American Psychiatric Pub. Retrieved 3 August Archives of Gynecology and Obstetrics. Birth Defects Research. Part B, Developmental and Reproductive Toxicology. BMC Medicine. Public Health Nutrition. Reproductive Health. Journal of Applied Physiology.
The American Journal of Physiology. A review". Scandinavian Journal of Gastroenterology. Welsh EJ ed.
Retrieved 2 January Journal of Human Nutrition and Dietetics. Renal Physiol. The claim: caffeine causes dehydration". New York Times. Exercise and Sport Sciences Reviews. Advances in Psychiatric Treatment. Expert Review of Neurotherapeutics. Psychological Medicine. Psychiatry, 2 Volume Set. Volume 1. Table Substance Dependence". Psychiatry and Pedopsychiatry. Prague: Karolinum Press. At a high dose, caffeine shows a euphoric effect. Encyclopedia of Behavioral Neuroscience. 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.
Pharmacology for health professionals 3rd ed. Chatswood, N. In contrast to the amphetamines, caffeine does not cause euphoria, stereotyped behaviors or psychoses. Neuropsychopharmacology and Therapeutics. 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.
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Elsevier Health Sciences. By comparison with amphetamines, methylxanthines produce less locomotor stimulation and do not induce euphoria, stereotyped behaviour patterns or a psychotic state, but their effects on fatigue and mental function are similar. Psychomotor stimulants Drugs that cause wakefulness and euphoria Amphetamines, cocaine, methylphenidate, caffeine.
Current Addiction Reports. McGraw-Hill Education. True compulsive use of caffeine has not been documented, and, consequently, these drugs are not considered addictive. Caffeine for youth? Time to act! Journal of Caffeine Research. Psychiatry Fourth ed. Archived from the original PDF on 22 December Dialogues in Clinical Neuroscience. Principles of addiction comprehensive addictive behaviors and disorders 1st ed.
Elsevier Academic Press. Retrieved 11 July Caffeine and arousal a biobehavioral theory of physiological behavioral and emotional effects. Is caffeine a drug of dependence? Caffeine withdrawal. Caffeine impulsivity and performance. Behavioral effects of caffeine the role of drugrelated expectancies. Caffeine and cognitive performance effects on mood or mental processing? Caffeine and attention. Caffeine and fatigue.
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The subjective effects of caffeine bridging the gap between animal and human research. Caffeine caffeine withdrawal and performance efficiency. The association of anxiety depression and headache with caffeine use.