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Caffeine is a central nervous system CNS stimulant of the methylxanthine class. Unlike many other psychoactive substances, it is legal and unregulated in nearly all parts of the world. There are several known mechanisms of action to explain the effects of caffeine. The most prominent is that it reversibly blocks the action of adenosine on its receptor and consequently prevents the onset of drowsiness induced by adenosine.
Caffeine also stimulates certain portions of the autonomic nervous system. 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, nuts, or leaves of a number of plants native to Africa, East Asia and South America,  and helps to protect them against predator insects and to prevent germination of nearby seeds.
Beverages containing caffeine are ingested to relieve or prevent drowsiness and to improve performance. To make these drinks, caffeine is extracted by steeping the plant product in water, a process called infusion. Caffeine can have both positive and negative health effects. It can treat and prevent the premature infant breathing disorders bronchopulmonary dysplasia of prematurity and apnea of prematurity. Evidence of a risk during pregnancy is equivocal; some authorities recommend that pregnant women limit consumption to the equivalent of two cups of coffee per day or less.
Toxic doses, over 10 grams per day for an adult, are much higher than the typical dose of under milligrams per day. Thus it requires roughly 50— 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 is a central nervous system stimulant that reduces fatigue and drowsiness. Caffeine can delay or prevent sleep and improves task performance during sleep deprivation.
A systematic review and meta-analysis from found that concurrent caffeine and L -theanine use has synergistic psychoactive effects that promote alertness, attention, and task switching ;  these effects are most pronounced during the first hour post-dose. Caffeine is a proven ergogenic aid in humans. Caffeine improves muscular strength and power,  and may enhance muscular endurance. While this effect is not present during to exhaustion exercise, performance is significantly enhanced.
This is congruent with caffeine reducing perceived exertion, because exercise to exhaustion should end at the same point of fatigue. In healthy children, caffeine intake produces effects that are "modest and typically innocuous". Based on average body weights of children, this translates to the following age-based intake limits: Health Canada has not developed advice for adolescents because of insufficient data.
However, they suggest that daily caffeine intake for this age group be no more than 2. This is because the maximum adult caffeine dose may not be appropriate for light-weight adolescents or for younger adolescents who are still growing. The daily dose of 2. This is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse effects. There are conflicting reports in the scientific literature about caffeine use during pregnancy.
Caffeine can increase blood pressure and cause vasoconstriction. Doses of caffeine equivalent to the amount normally found in standard servings of tea, coffee and carbonated soft drinks appear to have no diuretic action. However, chronic users of caffeine develop a tolerance to this effect and experience no increase in urinary output.
Minor undesired symptoms from caffeine ingestion not sufficiently severe to warrant a psychiatric diagnosis are common and include mild anxiety, jitteriness, insomnia, increased sleep latency, and reduced coordination. Increased consumption of coffee and caffeine is associated with a decreased risk of depression. Some textbooks state that caffeine is a mild euphoriant,    others state that it is not a euphoriant,   and one states that it is and is not a euphoriant.
Whether caffeine can result in an addictive disorder depends on how addiction is defined. Compulsive caffeine consumption under any circumstances has not been observed, and caffeine is therefore not generally considered addictive. Caffeine does not appear to be a reinforcing stimulus, and some degree of aversion may actually occur, with people preferring placebo over caffeine in a study on drug abuse liability published in an NIDA research monograph.
However, its addition was contested with claims that this diagnostic model of caffeine addiction is not supported by evidence. Withdrawal can cause mild to clinically significant distress or impairment in daily functioning. Tolerance to the effects of caffeine occurs for caffeine induced elevations in blood pressure and the subjective feelings of nervousness.
Sensitization , the process whereby effects become more prominent with use, occurs for positive effects such as feelings of alertness and well being. Non-regular caffeine users have the least caffeine tolerance for sleep disruption. A protective effect of caffeine against Alzheimer s disease and dementia is possible but the evidence is inconclusive. Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals.
Consumption of 1—1. Caffeine overdose can result in a state of central nervous system over-stimulation called caffeine intoxication DSM-IV The symptoms of caffeine intoxication are comparable to the symptoms of overdoses of other stimulants: Massive overdose can result in death. 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 it 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: 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. The world s primary source of caffeine is the coffee "bean" the seed of the coffee plant , from which coffee is brewed.
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