Caffeine is the most commonly used drug in the world. It is a naturally occurring substance found in coffee, tea, chocolate, and certain other plants; it is also frequently added to other products such as soda, energy drinks, over-the-counter cold medications, and weight-loss aids. Although consumption of small to moderate doses of caffeine is thought to be safe, some users become dependent on it and are unable to cut back despite problems caused by their intake.
Caffeine-related disorders include caffeine intoxication and caffeine withdrawal. Caffeine functions as a central nervous system stimulant and also a diuretic.
As a stimulant, caffeine can cause the heart to beat faster and hasten the effects of cold temperatures on the body. Contrary to a common myth, coffee will not sober up an inebriated person; instead, it typically causes agitation. Similarly, caffeine should never be given to a frostbite or hypothermia victim.
Once ingested, caffeine is absorbed and distributed quickly. After absorption, it passes into the brain. Caffeine does not accumulate in the bloodstream nor is it stored in the body. The effects of caffeine on health have been widely studied—in particular, its effects on fibrocystic breast disease, conditions of the heart and blood vessels, birth defects, reproductive function, and behavior in children. The American Medical Association Council on Scientific Affairs concludes, "Moderate tea or coffee drinkers probably have no concern for their health relative to their caffeine consumption provided other lifestyle habits diet , alcohol consumption are moderate as well.
Since caffeine affects different people in different ways, the definition of "overuse" can vary. Caffeine is defined as a drug because it is a central nervous system stimulant. Since caffeine-related disorder is not recognized as a diagnosable condition, there is no standardized treatment. It is generally recommended that children avoid caffeine use. Caffeinated beverages may be replacing nutrient-dense foods such as milk, and their consumption may interfere with the absorption of certain nutrients such as calcium and iron.
A child may also eat less after drinking caffeine because it acts as an appetite suppressant. 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 exercise-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.
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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.
Caffeine - Alcohol and Drug Foundation
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.
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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 : they may include restlessness, fidgeting, anxiety, excitement, insomnia, flushing of the face, increased urination, gastrointestinal disturbance, muscle twitching, a rambling flow of thought and speech, irritability, irregular or rapid heart beat, and psychomotor agitation.
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.
Caffeine is a natural stimulant
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.
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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.