Here is the first 'episode' of Caffeine, an incredibly broken game with the faintest glimmer of a decent premise.wherein absolutely nothing. Caffeine - Episode One Caffeine is a quirky psychological horror adventure game with an atmosphere heavily inspired by games like Condemned, FEAR and Outlast. Set in the near future, the entire population of Earth is vigorously addicted to coffee.
Key:RYYVLZVUVIJVGH-UHFFFAOYSA-N YSee also:Caffeine is a (CNS) of the. It is the world's most widely consumed. Unlike many other psychoactive substances, it is legal and unregulated in nearly all parts of the world. There are several known to explain the effects of caffeine. The most prominent is that it reversibly blocks the action of on and consequently prevents the onset of drowsiness induced by adenosine. Caffeine also stimulates certain portions of the.Caffeine is a bitter, white crystalline, a, and is chemically related to the and of (DNA) and (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. The most well-known source of caffeine is the, a for the seed of plants. People may drink containing caffeine to relieve or prevent drowsiness and to improve cognitive performance. To make these drinks, caffeine is extracted by the plant product in water, a process called.
Caffeine-containing drinks, such as, and, are very popular; as of 2014, 85% of American adults consumed some form of caffeine daily, consuming 164 mg on average.Caffeine can have both positive and negative health effects. It can treat and prevent the premature infant breathing disorders of prematurity. It may confer a modest protective effect against some diseases, including. Some people experience or anxiety if they consume caffeine, 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. Caffeine can produce a mild form of – associated with such as sleepiness, headache, and irritability – when an individual stops using caffeine after repeated daily intake. 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).Caffeine is classified by the US as (GRAS).
Toxic doses, over 10 grams per day for an adult, are much higher than the typical dose of under 500 milligrams per day. A cup of coffee contains 80–175 mg of caffeine, depending on what 'bean' (seed) is used and how it is prepared (e.g., or ). Thus it requires roughly 50–100 ordinary cups of coffee to reach the toxic dose. However, pure powdered caffeine, which is available as a, can be lethal in tablespoon-sized amounts.
Main article:Caffeine is used in:. in infants for both prevention and treatment. It may improve weight gain during therapy and reduce the incidence of cerebral palsy as well as reduce language and cognitive delay. On the other hand, subtle long-term side effects are possible.
as a primary treatment, but not prevention. treatment. Some people use caffeine-containing beverages such as coffee or tea to try to treat their asthma. Evidence to support this practice, however, is poor.
It appears that caffeine improves airway function in people with asthma, increasing (FEV1) by 5% to 18%, with this effect lasting for up to four hours. The caffeine in a cup of coffee (100–130 mg) improved when combined with or in 5-10% of people.Enhancing performance CognitiveCaffeine is a stimulant that reduces. At normal doses, caffeine has variable effects on learning and memory, but it generally improves, concentration,. The amount of caffeine needed to produce these effects varies from person to person, depending on body size and degree of tolerance. The desired effects arise approximately one hour after consumption, and the desired effects of a moderate dose usually subside after about three or four hours.Caffeine can delay or prevent and improves task performance during sleep deprivation. Shift workers who use caffeine make fewer mistakes due to drowsiness.A and from 2014 found that concurrent caffeine and use has synergistic psychoactive effects that promote alertness, attention, and; these effects are most pronounced during the first hour post-dose.
PhysicalCaffeine is a proven in humans. Caffeine improves athletic performance in (especially ) and conditions.
Moderate doses of caffeine (around 5 mg/kg ) can improve sprint performance, cycling and running time trial performance, endurance (i.e., it delays the onset of and ), and cycling power output. Caffeine increases in adults.Caffeine improves muscular strength and power, and may enhance muscular endurance. Caffeine also enhances performance on anaerobic tests. Caffeine consumption before constant load exercise is associated with reduced perceived exertion. 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. Caffeine also improves power output and reduces time to completion in aerobic time trials, an effect positively (but not exclusively) associated with longer duration exercise. Specific populations AdultsFor the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg. This limit was found to be safe by a 2017 systematic review on caffeine toxicology. ChildrenIn healthy children, moderate caffeine intake under 400 mg produces effects that are 'modest and typically innocuous'. Higher doses of caffeine (400 mg) can cause physiological, psychological and behavioral harm, particularly for children with psychiatric or cardiac conditions.
There is no evidence that coffee stunts a child's growth. 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: The recommends that caffeine consumption is not appropriate for children and adolescents and should be avoided.
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, Sports Medicine & Fitness committee, National Federations of High School Associations). Age rangeMaximum recommended daily caffeine intake4–645 mg (slightly more than in 12 oz of a typical caffeinated soft drink)7–962.5 mg10–1285 mg (about ½ cup of coffee)Adolescentshas not developed advice for adolescents because of insufficient data. However, they suggest that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight.
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 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse effects. Pregnancy and breastfeedingCurrent evidence regarding the effects of caffeine on pregnancy and for breastfeeding are inconclusive. There is limited primary and secondary advice for, or against, caffeine use during pregnancy and its effects on the fetus or newborn.The UK has recommended that pregnant women should limit their caffeine intake, out of prudence, to less than 200 mg of caffeine a day – the equivalent of two cups of instant coffee, or one and a half to two cups of fresh coffee. The (ACOG) concluded in 2010 that caffeine consumption is safe up to 200 mg per day in pregnant women.
For women who breastfeed, are pregnant, or may become pregnant, Health Canada recommends a maximum daily caffeine intake of no more than 300 mg, or a little over two 8 oz (237 mL) cups of coffee. A 2017 systematic review on caffeine toxicology found evidence supporting that caffeine consumption up to 300 mg/day for pregnant women is generally not associated with adverse reproductive or developmental effect.There are conflicting reports in the scientific literature about caffeine use during pregnancy. A 2011 review found that caffeine during pregnancy does not appear to increase the risk of, or even when consumed in moderate to high amounts. Other reviews, however, concluded that there is some evidence that higher caffeine intake by pregnant women may be associated with a higher risk of giving birth to a baby, and may be associated with a higher risk of pregnancy loss. A systematic review, analyzing the results of observational studies, suggests that women who consume large amounts of caffeine (greater than 300 mg/day) prior to becoming pregnant may have a higher risk of experiencing pregnancy loss.
Adverse effects PhysicalCoffee and caffeine can affect and secretion. Caffeine in low doses may cause weak bronchodilation for up to four hours in asthmatics. In postmenopausal women, high caffeine consumption can accelerate.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, acute ingestion of caffeine in large doses (at least 250–300 mg, equivalent to the amount found in 2–3 cups of coffee or 5–8 cups of tea) results in a short-term stimulation of urine output in individuals who have been deprived of caffeine for a period of days or weeks. This increase is due to both a (increase in water excretion) and a (increase in saline excretion); it is mediated via proximal tubular adenosine receptor blockade. The acute increase in urinary output may increase the risk of.
However, chronic users of caffeine develop a to this effect and experience no increase in urinary output. PsychologicalMinor 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. Caffeine can have negative effects on.
According to a 2011 literature review, caffeine use is positively associated with anxiety and panic disorders. At high doses, typically greater than 300 mg, caffeine can both cause and worsen anxiety. For some people, discontinuing caffeine use can significantly reduce anxiety. In moderate doses, caffeine has been associated with reduced symptoms of and lower risk.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.is a subclass of the diagnosis of substance/medication-induced anxiety disorder. Reinforcement disorders AddictionWhether 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. However, some diagnostic models, such as the and, include a classification of caffeine addiction under a broader diagnostic model.
Some state that certain users can become addicted and therefore unable to decrease use even though they know there are negative health effects.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 research monograph. Some state that research does not provide support for an underlying biochemical mechanism for caffeine addiction. Other research states it can affect the reward system.' Caffeine addiction' was added to the ICDM-9 and ICD-10. However, its addition was contested with claims that this diagnostic model of caffeine addiction is not supported by evidence.
The 's does not include the diagnosis of a caffeine addiction but proposes criteria for the disorder for more study. Dependence and withdrawal. See also:, andcan cause mild to clinically significant distress or impairment in daily functioning. The frequency at which this occurs is self-reported at 11%, but in lab tests only half of the people who report withdrawal actually experience it, casting doubt on many claims of dependence.
Mild and withdrawal symptoms may occur upon abstinence, with greater than 100 mg caffeine per day, although these symptoms last no longer than a day. Some symptoms associated with may also occur during withdrawal.
The diagnostic criteria for caffeine withdrawal require a previous prolonged daily use of caffeine. Following 24 hours of a marked reduction in consumption, a minimum of 3 of these signs or symptoms is required to meet withdrawal criteria: difficulty concentrating, /, -like symptoms,. Additionally, the signs and symptoms must disrupt important areas of functioning and are not associated with effects of another conditionThe ICD-11 includes as a distinct diagnostic category, which closely mirrors the ’s proposed set of criteria for “caffeine-use disorder”. Caffeine use disorder refers to dependence on caffeine characterized by failure to control caffeine consumption despite negative physiological consequences. The, which published the DSM-5, acknowledged that there was sufficient evidence in order to create a diagnostic model of caffeine dependence for the DSM-5, but they noted that the of the disorder is unclear.
Due to this inconclusive evidence on clinical significance, the DSM-5 classifies caffeine-use disorder as a “condition for further study”.to the effects of caffeine occurs for caffeine induced elevations in and the subjective feelings of nervousness., the process whereby effects become more prominent with use, occurs for positive effects such as feelings of alertness and well being. Tolerance varies for daily, regular caffeine users and high caffeine users. High doses of caffeine (750 to 1200 mg/day spread throughout the day) have been shown to produce complete tolerance to some, but not all of the effects of caffeine. Doses as low as 100 mg/day, such as a 6 oz cup of coffee or two to three 12 oz servings of caffeinated soft-drink, may continue to cause sleep disruption, among other intolerances. Non-regular caffeine users have the least caffeine tolerance for sleep disruption. Some coffee drinkers develop tolerance to its undesired sleep-disrupting effects, but others apparently do not.
Risk of other diseases. See also:A protective effect of caffeine against and dementia is possible but the evidence is inconclusive. It may protect people from. Caffeine may lessen the severity of if taken a few hours prior to attaining a high altitude.
One meta analysis has found that caffeine consumption is associated with a reduced risk of. Two meta analyses have reported that caffeine consumption is associated with a linear reduction in risk for. Caffeine consumption may be associated with reduced risk of, although conflicting results have been reported.Caffeine increases in those with but does not appear to affect normal individuals.The DSM-5 also includes other caffeine-induced disorders consisting of caffeine-induced anxiety disorder, caffeine-induced sleep disorder and unspecified caffeine-related disorders. The first two disorders are classified under “Anxiety Disorder” and “Sleep-Wake Disorder” because they share similar characteristics. Other disorders that present with significant distress and impairment of daily functioning that warrant clinical attention but do not meet the criteria to be diagnosed under any specific disorders are listed under “Unspecified Caffeine-Related Disorders”.
Primary symptoms of caffeine intoxicationConsumption of 1–1.5 grams (1,000–1,500 mg) per day is associated with a condition known as. Caffeinism usually combines caffeine with a wide range of unpleasant symptoms including nervousness, irritability, restlessness, insomnia, headaches, and palpitations after caffeine use.Caffeine overdose can result in a state of central nervous system over-stimulation known as caffeine intoxication, a clinically significant temporary condition that develops during, or shortly after, the consumption of caffeine.
This syndrome typically occurs only after ingestion of large amounts of caffeine, well over the amounts found in typical caffeinated beverages and caffeine tablets (e.g., more than 400–500 mg at a time). According to the DSM-5, caffeine intoxication may be diagnosed if five (or more) of the following symptoms develop after recent consumption of caffeine: restlessness, nervousness, excitement, insomnia, flushed face, diuresis (increased production of urine), gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia (increased heart rate) or cardiac arrythmia, periods of inexhaustibility, and psychomotor agitation.According to the International Classification of Diseases (ICD-11), cases of very high doses of caffeine (e.g. 5 g) may result in caffeine intoxication with symptoms including mania, depression, lapses in judgement, disorientation, disinhibition, delusions, hallucinations or psychosis, and rhabdomyolysis (breakdown of skeletal muscle tissue) can be provoked.Death from caffeine ingestion appears to be rare, and most commonly caused by an intentional overdose of medications. In 2016, 3702 caffeine related exposure were reported to Poison Control Centers in the United States, of which 846 required an hospitalization and 16 with a major outcome, and several caffeine-related deaths are reported in case studies. The of caffeine in humans is dependent on individual sensitivity, but is estimated to be 150–200 milligrams per kilogram (2.2 lb) of body mass (75–100 cups of coffee for a 70 kg (150 lb) adult).
There are cases where doses as low as 57 milligrams per kilogram being fatal. A number of fatalities have been caused by overdoses of readily available powdered caffeine supplements, for which the estimated lethal amount is less than a tablespoon.
The lethal dose is lower in individuals whose ability to metabolize caffeine is impaired due to genetics or chronic liver disease. A death was reported in a man with who overdosed on caffeinated mints.Since there is no antidote nor reversal agent for caffeine intoxication, treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require,. InteractionsCaffeine is a substrate for, and interacts with many substances through this and other mechanisms. See also:According to, alcohol provides a reduction in performance and caffeine has a significant improvement in performance. When alcohol and caffeine are consumed jointly, the effects produced by caffeine are affected, but the alcohol effects remain the same.
For example, when additional caffeine is added, the drug effect produced by alcohol is not reduced. However, the jitteriness and alertness given by caffeine is decreased when additional alcohol is consumed. Alcohol consumption alone reduces both inhibitory and activational aspects of behavioral control. Caffeine antagonizes the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control. The recommend avoidance of concomitant consumption of alcohol and caffeine, as this may lead to increased alcohol consumption, with a higher risk of alcohol-associated injury.TobaccoSmoking tobacco increases caffeine clearance by 56%. Birth controlcan extend the half-life of caffeine, requiring greater attention to caffeine consumption.
MedicationsCaffeine sometimes increases the effectiveness of some medications, such as those for. Caffeine was determined to increase the potency of some over-the-counter analgesic medications by 40%.The pharmacological effects of adenosine may be blunted in individuals taking large quantities of like caffeine. Pharmacology Pharmacodynamics Structure of a typical. Caffeine's primary mechanism of action is as an of receptors in the brainIn the absence of caffeine and when a person is awake and alert, little is present in (CNS) neurons. With a continued wakeful state, over time adenosine accumulates in the neuronal, in turn binding to and activating found on certain CNS neurons; when activated, these receptors produce a cellular response that ultimately increases. When caffeine is consumed, it 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. Receptor and ion channel targetsCaffeine is an of, and studies have specifically implicated antagonism of the A 2A receptor as responsible for the wakefulness-promoting effects of caffeine.
Antagonism of A2A receptors in the (VLPO) reduces inhibitory to the, a projection nucleus that activation-dependently promotes arousal. This disinhibition of the tuberomammillary nucleus is the downstream mechanism by which caffeine produces wakefulness-promoting effects. Caffeine is an antagonist of all four subtypes (, and ), although with varying. The values of caffeine for the human adenosine receptors are 12 μM at, 2.4 μM at, 13 μM at, and 80 μM at.Antagonism of adenosine receptors by caffeine also stimulates the vagal, vasomotor, and, which increases respiratory rate, reduces heart rate, and constricts blood vessels. Adenosine receptor antagonism also promotes neurotransmitter release (e.g., and ), which endows caffeine with its stimulant effects; acts as an inhibitory neurotransmitter that suppresses activity in the central nervous system. Are caused by blockade of the A 1 receptor.Because caffeine is both water- and lipid-soluble, it readily crosses the that separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action is as a nonselective 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.In addition to its activity at adenosine receptors, caffeine is an antagonist and a voltage-independent activator of the (, and ). It is also a competitive antagonist of the.
Effects on striatal dopamineWhile caffeine does not directly bind to any, it influences the binding activity of at its receptors in the by binding to adenosine receptors that have formed with dopamine receptors, specifically the – receptor (this is a receptor complex with 1 adenosine A 1 receptor and 1 dopamine D 1 receptor) and the – receptor (this is a receptor complex with 2 adenosine A 2A receptors and 2 dopamine D 2 receptors). The A 2A–D 2 receptor heterotetramer has been identified as a primary pharmacological target of caffeine, primarily because it mediates some of its psychostimulant effects and its pharmacodynamic interactions with dopaminergic psychostimulants.Caffeine also causes the release of dopamine in the and (a substructure within the ), but not the, by antagonizing receptors in the of dopamine neurons and – heterodimers (a receptor complex composed of 1 adenosine A 1 receptor and 1 adenosine A 2A receptor) in the axon terminal of glutamate neurons. During chronic caffeine use, caffeine-induced dopamine release within the nucleus accumbens core is markedly reduced due to. Enzyme targetsCaffeine, like other, also acts as a. As a competitive nonselective phosphodiesterase inhibitor, caffeine raises intracellular, activates, and synthesis,.
Caffeine also affects the where it inhibits the enzyme.Pharmacokinetics. Urinary metabolites of caffeine in humans at 48 hours post-dose.Caffeine from coffee or other beverages is absorbed by the small intestine within 45 minutes of ingestion and distributed throughout all bodily tissues. Peak blood concentration is reached within 1–2 hours. It is eliminated.
Caffeine can also be absorbed rectally, evidenced by suppositories of and caffeine (for the relief of ) and of and caffeine (for the treatment of ). However, rectal absorption is less efficient than oral: the maximum concentration and total amount absorbed are both about 30% (i.e., 1/3.5) of the oral amounts.Caffeine's – the time required for the body to eliminate one-half of a dose – varies widely among individuals according to factors such as pregnancy, other drugs, function level (needed for caffeine metabolism) and age. In healthy adults, caffeine's half-life is between 3 and 7 hours. Decreases the half-life by 30–50%, while can double it and pregnancy can raise it to as much as 15 hours during the third trimester. In newborns the half-life can be 80 hours or more, dropping very rapidly with age, possibly to less than the adult value by age 6 months. The antidepressant (Luvox) reduces the clearance of caffeine by more than 90%, and increases its elimination half-life more than tenfold; from 4.9 hours to 56 hours.Caffeine is in the by the enzyme system, in particular, by the isozyme, into three dimethyl, each of which has its own effects on the body:.
(84%): Increases, leading to elevated and free levels in. (12%): Dilates and increases volume. Theobromine is also the principal in the. (4%): Relaxes of the, and is used to treat. The of theophylline, however, is many times greater than the levels attained from caffeine metabolism.is a minor caffeine metabolite.
Each of these metabolites is further metabolized and then excreted in the urine. Caffeine can accumulate in individuals with severe, increasing its half-life.A 2011 review found that increased caffeine intake was associated with a variation in two genes that increase the rate of caffeine catabolism.
Subjects who had this on both consumed 40 mg more caffeine per day than others. This is presumably due to the need for a higher intake to achieve a comparable desired effect, not that the gene led to a disposition for greater incentive of habituation.ChemistryPure caffeine is a bitter-tasting, white, odorless powder with a melting point of 235–238 °C. Caffeine is moderately soluble in water at room temperature (2 g/100 mL), but very soluble in boiling water (66 g/100 mL). It is also moderately soluble in ethanol (1.5 g/100 mL). It is weakly basic (pK a of = 0.6) requiring strong acid to protonate it. Caffeine does not contain any centers and hence is classified as an molecule.The core of caffeine contains two fused rings, a. The pyrimidinedione in turn contains two functional groups that exist predominantly in a 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 and planar. Therefore, the fused 5,6 ring core of caffeine contains a total of ten and hence according to is. Fibrous of purified caffeine.
Image, about 7 mm × 11 mmExtraction of caffeine from coffee, to produce caffeine and decaffeinated coffee, can be performed using a number of solvents., and 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:. Water extraction: Coffee beans are soaked in water. The water, which contains many other compounds in addition to caffeine and contributes to the flavor of coffee, is then passed through, which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving decaffeinated coffee with its original flavor. Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter caffeine tablets. Supercritical carbon dioxide extraction: is an excellent nonpolar for caffeine, and is safer than the organic solvents that are otherwise used.
The extraction process is simple: CO2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73. Under these conditions, CO2 is in a ': It has gaslike properties that allow it to penetrate deep into the beans but also liquid-like properties that dissolve 97–99% of the caffeine. The caffeine-laden CO2 is then sprayed with high-pressure water to remove the caffeine. The caffeine can then be isolated by (as above) or by, or.
Extraction by organic solvents: Certain organic solvents such as 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.' Decaffeinated' coffees do in fact contain caffeine in many cases – some commercially available decaffeinated coffee products contain considerable levels. One study found that decaffeinated coffee contained 10 mg of caffeine per cup, compared to approximately 85 mg of caffeine per cup for regular coffee.
Detection in body fluidsCaffeine can be quantified in blood, plasma, or serum to monitor therapy in neonates, confirm a diagnosis of poisoning, or facilitate a medicolegal death investigation. Plasma caffeine levels are usually in the range of 2–10 mg/L in coffee drinkers, 12–36 mg/L in neonates receiving treatment for apnea, and 40–400 mg/L in victims of acute overdosage.
Urinary caffeine concentration is frequently measured in competitive sports programs, for which a level in excess of 15 mg/L is usually considered to represent abuse. AnalogsSome analog substances have been created which mimic caffeine's properties with either function or structure or both. Of the latter group are the and, which is an ingredient in. Members of a class of nitrogen substituted xanthines are often proposed as potential alternatives to caffeine.
Many other xanthine analogues constituting the adenosine receptor antagonist class have also been elucidated.Some other caffeine analogs:.Precipitation of tanninsCaffeine, as do other alkaloids such as, or, precipitates polyphenols. This property can be used in a quantitation method. Natural occurrence.
Roasted coffee beansAround sixty plant species are known to contain caffeine. Common sources are the 'beans' (seeds) of the two cultivated coffee plants, and (the quantity varies, but 1.3% is a typical value); in the leaves of the; and in. Other sources include leaves, South American holly leaves, seeds from Amazonian maple berries, and Amazonian holly leaves. Temperate climates around the world have produced unrelated caffeine-containing plants.Caffeine in plants acts as a natural: it can paralyze and kill predator insects feeding on the plant. High caffeine levels are found in coffee seedlings when they are developing foliage and lack mechanical protection. In addition, high caffeine levels are found in the surrounding soil of coffee seedlings, which inhibits seed germination of nearby coffee seedlings, thus giving seedlings with the highest caffeine levels fewer competitors for existing resources for survival.
Caffeine is stored in tea leaves in two places. Firstly, in the cell where it is complexed with. 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. Caffeine in nectar may improve the reproductive success of the producing plants by enhancing the reward memory of pollinators such as.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, including the stimulants and, and polyphenols that can form insoluble complexes with caffeine. No-Doz 100 mg caffeine tabletsTablets 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.
These tablets are commonly used by students studying for their exams and by people who work or drive for long hours. Other oral productsOne U.S. Company is marketing oral dissolvable caffeine strips.
Another intake route is, a caffeinated. Alert Energy Caffeine Gum was introduced in the United States in 2013, but was voluntarily withdrawn after an announcement of an investigation by the FDA of the health effects of added caffeine in foods. InhalantsThere are several products being marketed that offer inhalers that deliver proprietary blends of supplements, with caffeine being a key ingredient. In 2012, the FDA sent a warning letter to one of the companies marketing these inhalers, expressing concerns for the lack of safety information available about inhaled caffeine. Combinations with other drugs. Some beverages combine with caffeine to create a.
The stimulant effects of caffeine may mask the effects of alcohol, potentially reducing the user's awareness of their level of. Such beverages have been the subject of due to safety concerns. In particular, the has classified caffeine added to malt liquor beverages as an 'unsafe food additive'. contains a combination of and caffeine. Painkillers such as combine caffeine with an.History Discovery and spread of use.
Main articles:, andAccording to Chinese legend, the, reputed to have reigned in about 3000 BCE, inadvertently discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted. Shennong is also mentioned in Lu Yu's, a famous early work on the subject of tea.The earliest credible evidence of either coffee drinking or knowledge of the coffee plant appears in the middle of the fifteenth century, in the monasteries of the in southern Arabia. From, coffee spread to and North Africa, and by the 16th century, it had reached the rest of the Middle East,. 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 and to the Americas.use appears to have ancient origins. It is chewed in many cultures, in both private and social settings, to restore vitality and ease hunger pangs.The earliest evidence of use comes from residue found in an pot dated to 600 BCE.
Also, was consumed in a bitter and spicy drink called xocolatl, often seasoned with,. Xocolatl was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content. Chocolate was an important luxury good throughout, and cocoa beans were often used as currency. Xocolatl was introduced to by the, and became a popular beverage by 1700. The Spaniards also introduced the into the and the. It was used in processes, where it was known as 'black bean'. The leaves and stems of the yaupon holly ( ) were used by to brew a called asi or the '.
Archaeologists have found evidence of this use far into antiquity, possibly dating to. Chemical identification, isolation, and synthesis. See also:Recently discovered bacteria 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, various insects,. This is at least partly due to a poor ability to metabolize the compound, causing higher levels for a given dose per unit weight. Caffeine has also been found to enhance the reward memory of. ResearchCaffeine has been used to double chromosomes in. See also.References Notes.
Inhibitors: Reversible: Carbamates:.; Stigmines:.; Others:. Irreversible: Organophosphates:.; Others:.
(, ). ( ).
Unsorted:. Reactivators:.
Key:RYYVLZVUVIJVGH-UHFFFAOYSA-N YSee also:Caffeine is a (CNS) of the. It is the world's most widely consumed. Unlike many other psychoactive substances, it is legal and unregulated in nearly all parts of the world. There are several known to explain the effects of caffeine.
The most prominent is that it reversibly blocks the action of on and consequently prevents the onset of drowsiness induced by adenosine. Caffeine also stimulates certain portions of the.Caffeine is a bitter, white crystalline, a, and is chemically related to the and of (DNA) and (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. The most well-known source of caffeine is the, a for the seed of plants. People may drink containing caffeine to relieve or prevent drowsiness and to improve cognitive performance. To make these drinks, caffeine is extracted by the plant product in water, a process called. Caffeine-containing drinks, such as, and, are very popular; as of 2014, 85% of American adults consumed some form of caffeine daily, consuming 164 mg on average.Caffeine can have both positive and negative health effects.
It can treat and prevent the premature infant breathing disorders of prematurity. It may confer a modest protective effect against some diseases, including. Some people experience or anxiety if they consume caffeine, 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. Caffeine can produce a mild form of – associated with such as sleepiness, headache, and irritability – when an individual stops using caffeine after repeated daily intake.
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).Caffeine is classified by the US as (GRAS). Toxic doses, over 10 grams per day for an adult, are much higher than the typical dose of under 500 milligrams per day. A cup of coffee contains 80–175 mg of caffeine, depending on what 'bean' (seed) is used and how it is prepared (e.g., or ).
Thus it requires roughly 50–100 ordinary cups of coffee to reach the toxic dose. However, pure powdered caffeine, which is available as a, can be lethal in tablespoon-sized amounts. Main article:Caffeine is used in:. in infants for both prevention and treatment. It may improve weight gain during therapy and reduce the incidence of cerebral palsy as well as reduce language and cognitive delay. On the other hand, subtle long-term side effects are possible. as a primary treatment, but not prevention.
treatment. Some people use caffeine-containing beverages such as coffee or tea to try to treat their asthma. Evidence to support this practice, however, is poor. It appears that caffeine improves airway function in people with asthma, increasing (FEV1) by 5% to 18%, with this effect lasting for up to four hours. The caffeine in a cup of coffee (100–130 mg) improved when combined with or in 5-10% of people.Enhancing performance CognitiveCaffeine is a stimulant that reduces.
At normal doses, caffeine has variable effects on learning and memory, but it generally improves, concentration,. The amount of caffeine needed to produce these effects varies from person to person, depending on body size and degree of tolerance. The desired effects arise approximately one hour after consumption, and the desired effects of a moderate dose usually subside after about three or four hours.Caffeine can delay or prevent and improves task performance during sleep deprivation.
Shift workers who use caffeine make fewer mistakes due to drowsiness.A and from 2014 found that concurrent caffeine and use has synergistic psychoactive effects that promote alertness, attention, and; these effects are most pronounced during the first hour post-dose. PhysicalCaffeine is a proven in humans. Caffeine improves athletic performance in (especially ) and conditions.
Moderate doses of caffeine (around 5 mg/kg ) can improve sprint performance, cycling and running time trial performance, endurance (i.e., it delays the onset of and ), and cycling power output. Caffeine increases in adults.Caffeine improves muscular strength and power, and may enhance muscular endurance.
Caffeine also enhances performance on anaerobic tests. Caffeine consumption before constant load exercise is associated with reduced perceived exertion. 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. Caffeine also improves power output and reduces time to completion in aerobic time trials, an effect positively (but not exclusively) associated with longer duration exercise. Specific populations AdultsFor the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg. This limit was found to be safe by a 2017 systematic review on caffeine toxicology. ChildrenIn healthy children, moderate caffeine intake under 400 mg produces effects that are 'modest and typically innocuous'. Higher doses of caffeine (400 mg) can cause physiological, psychological and behavioral harm, particularly for children with psychiatric or cardiac conditions. There is no evidence that coffee stunts a child's growth.
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: The recommends that caffeine consumption is not appropriate for children and adolescents and should be avoided. 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, Sports Medicine & Fitness committee, National Federations of High School Associations). Age rangeMaximum recommended daily caffeine intake4–645 mg (slightly more than in 12 oz of a typical caffeinated soft drink)7–962.5 mg10–1285 mg (about ½ cup of coffee)Adolescentshas not developed advice for adolescents because of insufficient data. However, they suggest that daily caffeine intake for this age group be no more than 2.5 mg/kg body weight. 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 2.5 mg/kg body weight would not cause adverse health effects in the majority of adolescent caffeine consumers. This is a conservative suggestion since older and heavier weight adolescents may be able to consume adult doses of caffeine without suffering adverse effects. Pregnancy and breastfeedingCurrent evidence regarding the effects of caffeine on pregnancy and for breastfeeding are inconclusive. There is limited primary and secondary advice for, or against, caffeine use during pregnancy and its effects on the fetus or newborn.The UK has recommended that pregnant women should limit their caffeine intake, out of prudence, to less than 200 mg of caffeine a day – the equivalent of two cups of instant coffee, or one and a half to two cups of fresh coffee. The (ACOG) concluded in 2010 that caffeine consumption is safe up to 200 mg per day in pregnant women. For women who breastfeed, are pregnant, or may become pregnant, Health Canada recommends a maximum daily caffeine intake of no more than 300 mg, or a little over two 8 oz (237 mL) cups of coffee. A 2017 systematic review on caffeine toxicology found evidence supporting that caffeine consumption up to 300 mg/day for pregnant women is generally not associated with adverse reproductive or developmental effect.There are conflicting reports in the scientific literature about caffeine use during pregnancy.
A 2011 review found that caffeine during pregnancy does not appear to increase the risk of, or even when consumed in moderate to high amounts. Other reviews, however, concluded that there is some evidence that higher caffeine intake by pregnant women may be associated with a higher risk of giving birth to a baby, and may be associated with a higher risk of pregnancy loss. A systematic review, analyzing the results of observational studies, suggests that women who consume large amounts of caffeine (greater than 300 mg/day) prior to becoming pregnant may have a higher risk of experiencing pregnancy loss. Adverse effects PhysicalCoffee and caffeine can affect and secretion. Caffeine in low doses may cause weak bronchodilation for up to four hours in asthmatics.
In postmenopausal women, high caffeine consumption can accelerate.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, acute ingestion of caffeine in large doses (at least 250–300 mg, equivalent to the amount found in 2–3 cups of coffee or 5–8 cups of tea) results in a short-term stimulation of urine output in individuals who have been deprived of caffeine for a period of days or weeks.
This increase is due to both a (increase in water excretion) and a (increase in saline excretion); it is mediated via proximal tubular adenosine receptor blockade. The acute increase in urinary output may increase the risk of. However, chronic users of caffeine develop a to this effect and experience no increase in urinary output. PsychologicalMinor 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.
Caffeine can have negative effects on. According to a 2011 literature review, caffeine use is positively associated with anxiety and panic disorders. At high doses, typically greater than 300 mg, caffeine can both cause and worsen anxiety.
For some people, discontinuing caffeine use can significantly reduce anxiety. In moderate doses, caffeine has been associated with reduced symptoms of and lower risk.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.is a subclass of the diagnosis of substance/medication-induced anxiety disorder. Reinforcement disorders AddictionWhether 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. However, some diagnostic models, such as the and, include a classification of caffeine addiction under a broader diagnostic model. Some state that certain users can become addicted and therefore unable to decrease use even though they know there are negative health effects.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 research monograph.
Some state that research does not provide support for an underlying biochemical mechanism for caffeine addiction. Other research states it can affect the reward system.'
Caffeine addiction' was added to the ICDM-9 and ICD-10. However, its addition was contested with claims that this diagnostic model of caffeine addiction is not supported by evidence. The 's does not include the diagnosis of a caffeine addiction but proposes criteria for the disorder for more study. Dependence and withdrawal. See also:, andcan cause mild to clinically significant distress or impairment in daily functioning. The frequency at which this occurs is self-reported at 11%, but in lab tests only half of the people who report withdrawal actually experience it, casting doubt on many claims of dependence.
Mild and withdrawal symptoms may occur upon abstinence, with greater than 100 mg caffeine per day, although these symptoms last no longer than a day. Some symptoms associated with may also occur during withdrawal. The diagnostic criteria for caffeine withdrawal require a previous prolonged daily use of caffeine. Following 24 hours of a marked reduction in consumption, a minimum of 3 of these signs or symptoms is required to meet withdrawal criteria: difficulty concentrating, /, -like symptoms,. Additionally, the signs and symptoms must disrupt important areas of functioning and are not associated with effects of another conditionThe ICD-11 includes as a distinct diagnostic category, which closely mirrors the ’s proposed set of criteria for “caffeine-use disorder”. Caffeine use disorder refers to dependence on caffeine characterized by failure to control caffeine consumption despite negative physiological consequences. The, which published the DSM-5, acknowledged that there was sufficient evidence in order to create a diagnostic model of caffeine dependence for the DSM-5, but they noted that the of the disorder is unclear.
Due to this inconclusive evidence on clinical significance, the DSM-5 classifies caffeine-use disorder as a “condition for further study”.to the effects of caffeine occurs for caffeine induced elevations in and the subjective feelings of nervousness., the process whereby effects become more prominent with use, occurs for positive effects such as feelings of alertness and well being. Tolerance varies for daily, regular caffeine users and high caffeine users. High doses of caffeine (750 to 1200 mg/day spread throughout the day) have been shown to produce complete tolerance to some, but not all of the effects of caffeine.
Doses as low as 100 mg/day, such as a 6 oz cup of coffee or two to three 12 oz servings of caffeinated soft-drink, may continue to cause sleep disruption, among other intolerances. Non-regular caffeine users have the least caffeine tolerance for sleep disruption. Some coffee drinkers develop tolerance to its undesired sleep-disrupting effects, but others apparently do not.
Risk of other diseases. See also:A protective effect of caffeine against and dementia is possible but the evidence is inconclusive.
It may protect people from. Caffeine may lessen the severity of if taken a few hours prior to attaining a high altitude. One meta analysis has found that caffeine consumption is associated with a reduced risk of.
Two meta analyses have reported that caffeine consumption is associated with a linear reduction in risk for. Caffeine consumption may be associated with reduced risk of, although conflicting results have been reported.Caffeine increases in those with but does not appear to affect normal individuals.The DSM-5 also includes other caffeine-induced disorders consisting of caffeine-induced anxiety disorder, caffeine-induced sleep disorder and unspecified caffeine-related disorders. The first two disorders are classified under “Anxiety Disorder” and “Sleep-Wake Disorder” because they share similar characteristics. Other disorders that present with significant distress and impairment of daily functioning that warrant clinical attention but do not meet the criteria to be diagnosed under any specific disorders are listed under “Unspecified Caffeine-Related Disorders”.
Primary symptoms of caffeine intoxicationConsumption of 1–1.5 grams (1,000–1,500 mg) per day is associated with a condition known as. Caffeinism usually combines caffeine with a wide range of unpleasant symptoms including nervousness, irritability, restlessness, insomnia, headaches, and palpitations after caffeine use.Caffeine overdose can result in a state of central nervous system over-stimulation known as caffeine intoxication, a clinically significant temporary condition that develops during, or shortly after, the consumption of caffeine. This syndrome typically occurs only after ingestion of large amounts of caffeine, well over the amounts found in typical caffeinated beverages and caffeine tablets (e.g., more than 400–500 mg at a time). According to the DSM-5, caffeine intoxication may be diagnosed if five (or more) of the following symptoms develop after recent consumption of caffeine: restlessness, nervousness, excitement, insomnia, flushed face, diuresis (increased production of urine), gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech, tachycardia (increased heart rate) or cardiac arrythmia, periods of inexhaustibility, and psychomotor agitation.According to the International Classification of Diseases (ICD-11), cases of very high doses of caffeine (e.g. 5 g) may result in caffeine intoxication with symptoms including mania, depression, lapses in judgement, disorientation, disinhibition, delusions, hallucinations or psychosis, and rhabdomyolysis (breakdown of skeletal muscle tissue) can be provoked.Death from caffeine ingestion appears to be rare, and most commonly caused by an intentional overdose of medications. In 2016, 3702 caffeine related exposure were reported to Poison Control Centers in the United States, of which 846 required an hospitalization and 16 with a major outcome, and several caffeine-related deaths are reported in case studies. The of caffeine in humans is dependent on individual sensitivity, but is estimated to be 150–200 milligrams per kilogram (2.2 lb) of body mass (75–100 cups of coffee for a 70 kg (150 lb) adult).
There are cases where doses as low as 57 milligrams per kilogram being fatal. A number of fatalities have been caused by overdoses of readily available powdered caffeine supplements, for which the estimated lethal amount is less than a tablespoon.
The lethal dose is lower in individuals whose ability to metabolize caffeine is impaired due to genetics or chronic liver disease. A death was reported in a man with who overdosed on caffeinated mints.Since there is no antidote nor reversal agent for caffeine intoxication, treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require,. InteractionsCaffeine is a substrate for, and interacts with many substances through this and other mechanisms. See also:According to, alcohol provides a reduction in performance and caffeine has a significant improvement in performance.
When alcohol and caffeine are consumed jointly, the effects produced by caffeine are affected, but the alcohol effects remain the same. For example, when additional caffeine is added, the drug effect produced by alcohol is not reduced. However, the jitteriness and alertness given by caffeine is decreased when additional alcohol is consumed.
Alcohol consumption alone reduces both inhibitory and activational aspects of behavioral control. Caffeine antagonizes the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control. The recommend avoidance of concomitant consumption of alcohol and caffeine, as this may lead to increased alcohol consumption, with a higher risk of alcohol-associated injury.TobaccoSmoking tobacco increases caffeine clearance by 56%. Birth controlcan extend the half-life of caffeine, requiring greater attention to caffeine consumption. MedicationsCaffeine sometimes increases the effectiveness of some medications, such as those for. Caffeine was determined to increase the potency of some over-the-counter analgesic medications by 40%.The pharmacological effects of adenosine may be blunted in individuals taking large quantities of like caffeine.
Pharmacology Pharmacodynamics Structure of a typical. Caffeine's primary mechanism of action is as an of receptors in the brainIn the absence of caffeine and when a person is awake and alert, little is present in (CNS) neurons. With a continued wakeful state, over time adenosine accumulates in the neuronal, in turn binding to and activating found on certain CNS neurons; when activated, these receptors produce a cellular response that ultimately increases.
When caffeine is consumed, it 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. Receptor and ion channel targetsCaffeine is an of, and studies have specifically implicated antagonism of the A 2A receptor as responsible for the wakefulness-promoting effects of caffeine. Antagonism of A2A receptors in the (VLPO) reduces inhibitory to the, a projection nucleus that activation-dependently promotes arousal. This disinhibition of the tuberomammillary nucleus is the downstream mechanism by which caffeine produces wakefulness-promoting effects.
Caffeine is an antagonist of all four subtypes (, and ), although with varying. The values of caffeine for the human adenosine receptors are 12 μM at, 2.4 μM at, 13 μM at, and 80 μM at.Antagonism of adenosine receptors by caffeine also stimulates the vagal, vasomotor, and, which increases respiratory rate, reduces heart rate, and constricts blood vessels.
Adenosine receptor antagonism also promotes neurotransmitter release (e.g., and ), which endows caffeine with its stimulant effects; acts as an inhibitory neurotransmitter that suppresses activity in the central nervous system. Are caused by blockade of the A 1 receptor.Because caffeine is both water- and lipid-soluble, it readily crosses the that separates the bloodstream from the interior of the brain.
Once in the brain, the principal mode of action is as a nonselective 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.In addition to its activity at adenosine receptors, caffeine is an antagonist and a voltage-independent activator of the (, and ). It is also a competitive antagonist of the. Effects on striatal dopamineWhile caffeine does not directly bind to any, it influences the binding activity of at its receptors in the by binding to adenosine receptors that have formed with dopamine receptors, specifically the – receptor (this is a receptor complex with 1 adenosine A 1 receptor and 1 dopamine D 1 receptor) and the – receptor (this is a receptor complex with 2 adenosine A 2A receptors and 2 dopamine D 2 receptors). The A 2A–D 2 receptor heterotetramer has been identified as a primary pharmacological target of caffeine, primarily because it mediates some of its psychostimulant effects and its pharmacodynamic interactions with dopaminergic psychostimulants.Caffeine also causes the release of dopamine in the and (a substructure within the ), but not the, by antagonizing receptors in the of dopamine neurons and – heterodimers (a receptor complex composed of 1 adenosine A 1 receptor and 1 adenosine A 2A receptor) in the axon terminal of glutamate neurons.
During chronic caffeine use, caffeine-induced dopamine release within the nucleus accumbens core is markedly reduced due to. Enzyme targetsCaffeine, like other, also acts as a.
As a competitive nonselective phosphodiesterase inhibitor, caffeine raises intracellular, activates, and synthesis,. Caffeine also affects the where it inhibits the enzyme.Pharmacokinetics. Urinary metabolites of caffeine in humans at 48 hours post-dose.Caffeine from coffee or other beverages is absorbed by the small intestine within 45 minutes of ingestion and distributed throughout all bodily tissues. Peak blood concentration is reached within 1–2 hours. It is eliminated.
Caffeine can also be absorbed rectally, evidenced by suppositories of and caffeine (for the relief of ) and of and caffeine (for the treatment of ). However, rectal absorption is less efficient than oral: the maximum concentration and total amount absorbed are both about 30% (i.e., 1/3.5) of the oral amounts.Caffeine's – the time required for the body to eliminate one-half of a dose – varies widely among individuals according to factors such as pregnancy, other drugs, function level (needed for caffeine metabolism) and age. In healthy adults, caffeine's half-life is between 3 and 7 hours. Decreases the half-life by 30–50%, while can double it and pregnancy can raise it to as much as 15 hours during the third trimester.
In newborns the half-life can be 80 hours or more, dropping very rapidly with age, possibly to less than the adult value by age 6 months. The antidepressant (Luvox) reduces the clearance of caffeine by more than 90%, and increases its elimination half-life more than tenfold; from 4.9 hours to 56 hours.Caffeine is in the by the enzyme system, in particular, by the isozyme, into three dimethyl, each of which has its own effects on the body:.
(84%): Increases, leading to elevated and free levels in. (12%): Dilates and increases volume.
Theobromine is also the principal in the. (4%): Relaxes of the, and is used to treat. The of theophylline, however, is many times greater than the levels attained from caffeine metabolism.is a minor caffeine metabolite. Each of these metabolites is further metabolized and then excreted in the urine. Caffeine can accumulate in individuals with severe, increasing its half-life.A 2011 review found that increased caffeine intake was associated with a variation in two genes that increase the rate of caffeine catabolism.
Subjects who had this on both consumed 40 mg more caffeine per day than others. This is presumably due to the need for a higher intake to achieve a comparable desired effect, not that the gene led to a disposition for greater incentive of habituation.ChemistryPure caffeine is a bitter-tasting, white, odorless powder with a melting point of 235–238 °C. Caffeine is moderately soluble in water at room temperature (2 g/100 mL), but very soluble in boiling water (66 g/100 mL). It is also moderately soluble in ethanol (1.5 g/100 mL). It is weakly basic (pK a of = 0.6) requiring strong acid to protonate it.
Caffeine does not contain any centers and hence is classified as an molecule.The core of caffeine contains two fused rings, a. The pyrimidinedione in turn contains two functional groups that exist predominantly in a 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 and planar. Therefore, the fused 5,6 ring core of caffeine contains a total of ten and hence according to is.
Fibrous of purified caffeine. Image, about 7 mm × 11 mmExtraction of caffeine from coffee, to produce caffeine and decaffeinated coffee, can be performed using a number of solvents., and 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:.
Water extraction: Coffee beans are soaked in water. The water, which contains many other compounds in addition to caffeine and contributes to the flavor of coffee, is then passed through, which removes the caffeine. The water can then be put back with the beans and evaporated dry, leaving decaffeinated coffee with its original flavor. Coffee manufacturers recover the caffeine and resell it for use in soft drinks and over-the-counter caffeine tablets. Supercritical carbon dioxide extraction: is an excellent nonpolar for caffeine, and is safer than the organic solvents that are otherwise used. The extraction process is simple: CO2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73.
Under these conditions, CO2 is in a ': It has gaslike properties that allow it to penetrate deep into the beans but also liquid-like properties that dissolve 97–99% of the caffeine. The caffeine-laden CO2 is then sprayed with high-pressure water to remove the caffeine. The caffeine can then be isolated by (as above) or by, or. Extraction by organic solvents: Certain organic solvents such as 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.' Decaffeinated' coffees do in fact contain caffeine in many cases – some commercially available decaffeinated coffee products contain considerable levels. One study found that decaffeinated coffee contained 10 mg of caffeine per cup, compared to approximately 85 mg of caffeine per cup for regular coffee.
Detection in body fluidsCaffeine can be quantified in blood, plasma, or serum to monitor therapy in neonates, confirm a diagnosis of poisoning, or facilitate a medicolegal death investigation. Plasma caffeine levels are usually in the range of 2–10 mg/L in coffee drinkers, 12–36 mg/L in neonates receiving treatment for apnea, and 40–400 mg/L in victims of acute overdosage. Urinary caffeine concentration is frequently measured in competitive sports programs, for which a level in excess of 15 mg/L is usually considered to represent abuse. AnalogsSome analog substances have been created which mimic caffeine's properties with either function or structure or both. Of the latter group are the and, which is an ingredient in. Members of a class of nitrogen substituted xanthines are often proposed as potential alternatives to caffeine.
Many other xanthine analogues constituting the adenosine receptor antagonist class have also been elucidated.Some other caffeine analogs:.Precipitation of tanninsCaffeine, as do other alkaloids such as, or, precipitates polyphenols. This property can be used in a quantitation method. Natural occurrence. Roasted coffee beansAround sixty plant species are known to contain caffeine.
Common sources are the 'beans' (seeds) of the two cultivated coffee plants, and (the quantity varies, but 1.3% is a typical value); in the leaves of the; and in. Other sources include leaves, South American holly leaves, seeds from Amazonian maple berries, and Amazonian holly leaves. Temperate climates around the world have produced unrelated caffeine-containing plants.Caffeine in plants acts as a natural: it can paralyze and kill predator insects feeding on the plant. High caffeine levels are found in coffee seedlings when they are developing foliage and lack mechanical protection. In addition, high caffeine levels are found in the surrounding soil of coffee seedlings, which inhibits seed germination of nearby coffee seedlings, thus giving seedlings with the highest caffeine levels fewer competitors for existing resources for survival. Caffeine is stored in tea leaves in two places. Firstly, in the cell where it is complexed with.
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. Caffeine in nectar may improve the reproductive success of the producing plants by enhancing the reward memory of pollinators such as.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, including the stimulants and, and polyphenols that can form insoluble complexes with caffeine. No-Doz 100 mg caffeine tabletsTablets 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. These tablets are commonly used by students studying for their exams and by people who work or drive for long hours.
Other oral productsOne U.S. Company is marketing oral dissolvable caffeine strips. Another intake route is, a caffeinated. Alert Energy Caffeine Gum was introduced in the United States in 2013, but was voluntarily withdrawn after an announcement of an investigation by the FDA of the health effects of added caffeine in foods. InhalantsThere are several products being marketed that offer inhalers that deliver proprietary blends of supplements, with caffeine being a key ingredient. In 2012, the FDA sent a warning letter to one of the companies marketing these inhalers, expressing concerns for the lack of safety information available about inhaled caffeine.
Combinations with other drugs. Some beverages combine with caffeine to create a. The stimulant effects of caffeine may mask the effects of alcohol, potentially reducing the user's awareness of their level of.
Such beverages have been the subject of due to safety concerns. In particular, the has classified caffeine added to malt liquor beverages as an 'unsafe food additive'. contains a combination of and caffeine. Painkillers such as combine caffeine with an.History Discovery and spread of use. Main articles:, andAccording to Chinese legend, the, reputed to have reigned in about 3000 BCE, inadvertently discovered tea when he noted that when certain leaves fell into boiling water, a fragrant and restorative drink resulted.
Shennong is also mentioned in Lu Yu's, a famous early work on the subject of tea.The earliest credible evidence of either coffee drinking or knowledge of the coffee plant appears in the middle of the fifteenth century, in the monasteries of the in southern Arabia. From, coffee spread to and North Africa, and by the 16th century, it had reached the rest of the Middle East,.
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 and to the Americas.use appears to have ancient origins. It is chewed in many cultures, in both private and social settings, to restore vitality and ease hunger pangs.The earliest evidence of use comes from residue found in an pot dated to 600 BCE.
Also, was consumed in a bitter and spicy drink called xocolatl, often seasoned with,. Xocolatl was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content. Chocolate was an important luxury good throughout, and cocoa beans were often used as currency. Xocolatl was introduced to by the, and became a popular beverage by 1700. The Spaniards also introduced the into the and the. It was used in processes, where it was known as 'black bean'.
The leaves and stems of the yaupon holly ( ) were used by to brew a called asi or the '. Archaeologists have found evidence of this use far into antiquity, possibly dating to. Chemical identification, isolation, and synthesis.
See also:Recently discovered bacteria 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, various insects,. This is at least partly due to a poor ability to metabolize the compound, causing higher levels for a given dose per unit weight. Caffeine has also been found to enhance the reward memory of. ResearchCaffeine has been used to double chromosomes in. See also.References Notes. Inhibitors: Reversible: Carbamates:.; Stigmines:.; Others:.
Irreversible: Organophosphates:.; Others:. (, ). ( ).
Unsorted:. Reactivators:.