Key:RYYVLZVUVIJVGH-UHFFFAOYSA-N Y See 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 its receptor and consequently prevents the onset of drowsiness induced by adenosine. Caffeine also stimulates certain portions of the.

The effects of a number of calcium antagonists (diltiazem, nifedipine, nimodipine and verapamil) have been studied on feline isolated pial arteries. Arterial segments were dissected free and placed in a glass beaker containing the cold buffer. Tracellular effects (Church & Zsot&r, 1980). They may attenuate the release of.

Caffeine is a bitter, white crystalline, a, and is chemically related to the and bases of (DNA) and (RNA). It is found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia 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. Containing caffeine are ingested to relieve or prevent drowsiness and to improve 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 and. It may confer a modest protective effect against some diseases, including. Some people experience or sleep disruption if they consume caffeine, especially during the evening hours, but others show little disturbance. 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.

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 typical doses 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 a lethal dose. However pure powdered caffeine, which is available as a, can be lethal in tablespoon-sized amounts.

Contents • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Use Medical 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. Enhancing performance Cognitive Caffeine is a stimulant that reduces and. At normal doses, caffeine has variable effects on learning and memory, but it generally improves,, concentration, and. 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.

Physical Caffeine 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. Specific populations Adults For the general population of healthy adults, Health Canada advises a daily intake of no more than 400 mg. Children In healthy children, caffeine intake produces effects that are 'modest and typically innocuous'. 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: Age range Maximum recommended daily caffeine intake 4–6 45 mg (slightly more than in 12 oz of a typical soft drink) 7–9 62.5 mg 10–12 85 mg (about ½ cup of coffee) Adolescents 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 2.5 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 breastfeeding 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.

The evidence for or against the importance of limiting caffeine intake during pregnancy is insufficient and of low quality. There are conflicting reports in the scientific literature about caffeine consumption during pregnancy. A 2011 risk analysis review found that caffeine consumption during pregnancy does not appear to increase the risk of, or even when consumed in moderate to high amounts. There is some evidence that the hormonal changes during pregnancy slow the metabolic clearance of caffeine from the system, causing a given dose to have longer-lasting effects (as long as 15 hours in the third trimester). 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.

Side effects Physical Caffeine can increase blood pressure and cause. Coffee and caffeine can affect and secretion.

Caffeine in low doses may cause weak bronchodilation for up to four hours in asthmatics. Caffeine increases in adults. 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. Psychological 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.

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 may reduce symptoms of and lower risk. 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. Reinforcement disorders Addiction Whether or not caffeine can result in an addictive disorder depends on how addiction is defined. 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 NIDA 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. Main article: can 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 to increasingly severe and withdrawal symptoms may occur upon abstinence, with greater than 100 mg caffeine per day; some symptoms associated with may also occur during. Caffeine dependence can involve withdrawal symptoms such as fatigue, headache, irritability, depressed mood, reduced contentedness, inability to concentrate, sleepiness or drowsiness,, and. Withdrawal headaches are experienced by roughly half of those who stop consuming caffeine for two days following an average daily intake of 235 mg. The ICD-10 includes a diagnostic model for, but the DSM-5 does not. 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 this disorder is unclear.

The DSM-5 instead lists 'caffeine use disorder' in the section of the manual. 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. Primary symptoms of caffeine intoxication Consumption of 1–1.5 grams per day is associated with a condition known as caffeinism. 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 called caffeine intoxication ( 305.90). 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). The symptoms of caffeine intoxication are comparable to the symptoms of overdoses of other: 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. In cases of much larger overdoses,,, lapses in judgment,,, delusions, hallucinations, or psychosis may occur, and (breakdown of skeletal muscle tissue) can be provoked.

Massive overdose can result in death. The of caffeine in humans is dependent on individual sensitivity, but is estimated to be 150 to 200 milligrams per kilogram of body mass (75–100 cups of coffee for a 70 kilogram adult).

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. Treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require,,. Interactions Alcohol. 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. Tobacco Smoking tobacco increases caffeine clearance by 56%. Birth control can extend the half-life of caffeine, requiring greater attention to caffeine consumption.

Medications Caffeine sometimes increases the effectiveness of some medications, such as those for. Pharmacology Pharmacodynamics Structure of a typical. Caffeine's primary mechanism of action is as an of receptors in the brain In 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 it 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 targets Caffeine is an at all four subtypes (,,, and ), although with varying. The () values of caffeine for the human adenosine receptors are 12 μM at, 2. Helveticaneue Boldcond Font Download there. 4 μM at, 13 μM at, and 80 μM. Studies have specifically implicated antagonism of the A 2A receptor as responsible for the wakefulness-promoting effects of caffeine.

Antagonism of adenosine receptors by caffeine 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 (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 dopamine While 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 targets Caffeine, like other, also acts as a. As a competitive nonselective, caffeine raises intracellular, activates, and synthesis, and and. Caffeine also affects the where it inhibits the enzyme. Off-target effects Caffeine antagonizes in the (VLPO), thereby reducing inhibitory to the, a projection nucleus that activation-dependently promotes arousal.

Disinhibition of the tuberomammillary nucleus is the chief mechanism by which caffeine produces wakefulness-promoting effects. 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 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 3–7 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 last 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.

Chemistry Pure 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 and. The pyrimidinedione in turn contains two functional groups that exist predominately 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, the image covers an area of approx. Extraction 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: CO 2 is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73. Under these conditions, CO 2 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 CO 2 is then sprayed with high pressure water to remove the caffeine. The caffeine can then be isolated by (as above) or by,,. • 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 fluids 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. 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. Analogs Some 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 tannins Caffeine, as do other alcaloids such as, or, precipitates polyphenols and.This property can be used in a quantitation method. Natural occurrence. Roasted coffee beans Around 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. [ ] Products.

No-Doz 100 mg caffeine tablets Tablets offer the advantages over coffee and tea of convenience, known dosage, and avoiding concomitant sugar, acid and fluid intake. 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 products One 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. Inhalants There 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, has classified caffeine added to malt liquor beverages as an 'unsafe food additive'. • contains a combination of and caffeine. History Discovery and spread of use. Main articles:,,, and According to Chinese legend, the, reputed to have reigned in about 3000 BCE, accidentally 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 tree appears in the middle of the fifteenth century, in the monasteries of the southern Arabia.

From, coffee spread to and North Africa, and by the 16th century, it had reached the rest of the Middle East, and. 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, individually or in a social setting, 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,, and. 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, and. 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. Research Caffeine has been used to double chromosomes in. See also • • References.

• Agonists: • • • • • • • • • • • • • • • • • • • • • Positive modulators: (e.g.,,,,,,, ) • • • (e.g.,, ) • • • (e.g., ) • • constituents (e.g., (e.g., )) • • • • (e.g.,,,,, ) • • • • • • • (e.g.,,,,,, ) • / (e.g.,,,,,,,,,,,, ) • • • Antagonists: • • • • • • • • • • • • • (e.g.,, ) • • • • • • • • • • • • • • (e.g.,,,,,, ) • • • • • • Negative modulators: • (e.g.,,,,, ) • • • • (e.g.,,, ) • • • constituents (e.g.,, (e.g.,,,,, )) • • • (e.g.,,,,,, ) • (e.g.,,,,,,,,, ) • (i.e., and ) • • • (e.g.,,,, ) • •.

A disturbing scene in the 2014 movie Kingsman: The Secret Service features the hero killing an entire congregation inside a Baptist-style church in the Southern U.S. Similar to the one in Texas. On November 5th, Devin Kelley entered the First Baptist Church of a small town in Texas during the Sunday service, while wearing a skull mask and a ballistic vest. Armed with a Ruger AR-556 rifle and two handguns, Kelley fired into the crowd, killing 26 people, including several children. Devin Kelley Not unlike several mass shooters in the past, Devin Kelley had served in the military for some time, including a 12-month stint in confinement. Kelley was once a member of the US Air Force, spokeswoman Ann Stefanek said. He served in logistics readiness at Holloman Air Force Base in New Mexico, starting in 2010.

Kelley was court-martialed in 2012 for two counts of Article 128 of the Uniform Code of Military Justice, assault on his spouse and assault on their child, Stefanek said. Kelley received a bad conduct discharge, confinement for 12 months and a reduction in rank, she said. The Air Force did not provide a date of the discharge. – CNN, What we know about Texas church shooting suspect Devin Patrick Kelley Various accounts about Kelley are surfacing in mass media.

Some news reports state that he was an “aggressive atheist” who often took to social media. His Linkedin profile states that he was an ex –Bible studies teacher, which is somewhat contradictory with shooting up a church.

Both his family and his wife had strong ties to the church. According to a profile on Indeed.com, Kelley’s wife was a “teacher for toddlers” at First Baptist of Sutherland Springs from June of 2009 to March of 2013. Her responsibilities included teaching the children about God, helping with “their life stones that are needed,” and being a “positive influence in their life,” the page. – Heavy, Danielle Shields Kelley: 5 Fast Facts You Need to Know New police reports state that Kelley had “issues” with his mother-in-law who usually attends the church, but she was not present that day. So what truly motivated the shooter to kill?

Could he have been programmed in the military to carry out this horrific mission? The public was certainly programmed to witness it. Describing the horrific scene in Sutherland Springs, Wilson County Sheriff Joe Tackitt stated: “He just walked down the center aisle, turned around and my understanding was shooting on his way back out. It’s unbelievable to see children, men and women, laying there. DefenSeless people.” The First Baptist Church in Texas. That scenario is eerily similar to a scene in the movie Kingsman: The Secret Service. Even the church is similar.

The congregation of the church worships in Kingsman: The Secret Service Galahad, one of the lead characters in the film, gets up during the sermon and tells a woman: “I’m a Catholic w**Re who’s currently enjoying congress out of wedlock with my black Jewish boyfriend who works in a military abortion clinic. So, hail Satan and have a lovely afternoon madam”. Galahad then proceeds to kill every single person in the church, in a long, dragged-out, extremely gory scene with rock music playing in the background. Galahad shoots a woman in the head. In the end, he kills every single person in the church. Oh and he is the good guy. As Galahad leaves South Glade Mission Church, we see a gloomy message: America is doomed.

In my article, I explained how this entire movie discloses the elite’s agenda. It even ends with the world’s elite hiding in a remote location as the masses get slaughtered.

In the movie, Galahad’s murderous spree is explained by him being “mind-controlled” by a chip on his phone. Was Kelley mind-controlled as well? One thing is for sure, the killing of people while they are actively worshipping God is, on a spiritual level, extremely powerful. Killed While Worshipping People of Christian faith call their church the “house of God”. Inside the house of God, they pray and commune with God. For many, it is a sacred and solemn moment of intense spirituality. To enter the house of God and turn it into a bloodbath while the congregation is in active worship is effectively, on a spiritual level, a satanic ritual.

As seen above, in Kingsman, right before killing everyone worshipping in a church, Galahad actually says “Hail Satan”. The mass media synchronicities do not stop there. The “revoltingly violent” series Preacher takes place in Texas. The official poster features an upside-down church which forces us to see an inverted cross: A symbol of satanism. Only hours after the church shooting, Marilyn Manson (a stated member of the Church of Satan) appeared on stage pointing a fake rifle at his audience.

The rifle has an inverted Cross of Lorraine on it. The concert took place in San Bernardino, a city that experienced a mass shooting in December 2015. The Normalization of Horror Two of the deadliest mass shootings in American history have happened in the last 35 days. In the wake of these tragedies, as if it has become a new custom, many immediately took to social media to instrumentalize the tragedy, using it to justify their political agenda, while bypassing any kind of human consideration in the process. The only way to counteract the elite is to boycott EVERYTHING: Big corporates, Big pharma, ALL mainstream media, music, movies, television – EVERYTHING!!!

Don’t support. It’s that simple. Start looking at living with less and consider going back to your ‘roots’. Like Vigilant says, we are ALL to blame for the condition of the world we are in because we willingly buy into their agenda by supporting them and their products/services/lies/propaganda etc. We are ALL ONE people!

The 99% of us are all that is needed to end this. How can 1% continue controlling us?? It’s totally ludicrous to think that we willingly sell our souls through our constant ‘need’ for more and more and more. Less IS more! It’s time to take back our divine sovereignty and to stop separating ourselves from each other.

These false flag attacks and stuff gives us a blessing in disguise: Read more ». It’s safe to say that most people on this site probably have eliminated a lot of things enumerated here. Now how do we get the other 99.9% of westerners to listen? To even see that their creature comforts and entertainment are poisoning humanity? And then, in the unlikely circumstance that they even agree on the premise that these things are toxic, actually give them up?

I hate to sound like a wet blanket, but there is actually much more in the world than just love; the world is vastly more complicated than simply “love”. Life is far more layered and intricately woven. A continual pattern we see is pain, tragedy and heartbreak- though humans are exceptionally good at adjusting to these situations and often, but not always, overcoming them.

Of course, love is indescribably important. With love and peace, a commenter. Life exists by consuming life.

Even plants use their skills to survive, sometimes with destroying other plantlife. We humans are supposed to be top of the foodchain, but we still need to eat plants, life, and animals, life, to survive. The way we do it matters. Destroying other peoples lifes to survive or to enhance your own life is an abstract form of cannibalism.

I assume that’s been around as long as there is a form of human life, too. Love might even be last on the list of skills of those without empathy or the ability to use their empathy. Now, how to improve ourselves And our global societies? How to cope with an unsafe world where the next generation is a are a threat to our own wellbeing? No one is going to do those. We’ve been watching, listening, reading, following their pushes for years.

I myself have been been reading VC since his Jay-Z On To The Next One article. What about 10 yrs? I myself has read through comments, rants, complaints, n compliments. But, I have NOT read any action of any reader( that I am aware of.) My “blind” neighbors n friends AND yinz smart “aware” ones all in the SAME world — — And no one is doing anything to shield and protect our children. Now ones doing anything. I’ve been trying to teach my daughter for 10 years l about the symbols and being vigilant and media and more.

Sigh She’s 13 today and I still can’t protect her from it: /. I don’t own a TV,nor do i listen to music or watch films for th last 6-7years. My kids don’t do Disney and hav never tasted McDonalds,KFC or any other junky stuff. It’s sad that when I do all this,as a Muslim woman protecting herself n her family,i am declared ‘backwards’ n ‘oppressed’ bt a non-Muslim suggest the same, and every1 concurs regardless, we’v been warned abt all of this, signs of the end times, in the Torah, Bible and Qur’an, and it’s time we listened. Read your book,we are ONE nation,whether we like it or not, the elite ‘divide and conquer’, read your book! Trump is no resistance leader.

Get that into your head you dumb ‘nationalist’. It’s the same old tactic used by the hardcore Zionist socialists and the Catholic Church ( actually a front for a version of the Roman Empire controlled by modern-day Pharisees) to create the State of Isreal and put mankind in its current state of affairs.

Arduino Multiple Serial Values. Stalin decided to separate Communism from Zionism and fuse it with Slavic nationalism to solidify his power among the people. (JFK tried a similar tactic but decided to add Christianity to the mix. That’s why the Russians failed to stop the hit team when it was found an Oswald double had called a the top Soviet man for assassination some time before, and passed off their knowledge as disinformation later on.) Of course the Zionists were enraged at this tactic. The Catholic heiracy and the Zionists remembered the days of Read more ». Military background. Held in solitary for one year.

Dishonorably discharged five years ago. Sounds like the perfect MK’d “soldier” to keep around on “stand by” and when the time is ready, trigger him to pull the trigger. There are some interesting tweets that point to Devin (the shooter) being part of Antifa and that he was upset that the promised Resistance Day on November 4th didn’t happen. So he decided to take it upon himself to kill people at a church.something that Antifa (a George Soros creation) “promised to do” on November 4th. Connect the dots there and see how this guy could have easily been “used”. Here’s the link to the Twitter account I was referring to. The one about Antifa shooting up churches is somewhere in the thread.

I saw it yesterday but I can’t find it now. Not in the US.

In Europe, the international communists created antifa because they felt the wrong group of socialists had taken power, the National Socialists. They’d both generally believed in the same ultimate goal, a Socialist European super-state, but they fought over which group of elite socialists would control this monstrosity. After the fall of the National Socialists, antifa folded back in to the communist movement and was used as a blunt force tool in the communists’ plans in Europe during the Cold War. Soros invented the US version by combining the paid professional protesters from the 99%, Occupy, BLM, “Anarchist,” and anti-war rallies/protests, pumping them full of money, and connecting them with the extreme left within the establishment, especially socialists in the Democratic Party and socialists in education. Soros wanted to bring idiot revolutionaries into the US system because it worked very well for him in Europe. Soros basically Read more ». People always come out after a HOAX all the time saying a cousin, a friend or an acquaintance I know was actually shot.

Especially on YouTube comment boards and it’s always an account that was created the same day when they post this. That’s a good way to get mocked because people joke all the time now with saying things like “well my third cousin’s kindergarten teacher’s brother in law’s gardner was shot there,” regardless if true. This happens on obvious HOAXES like Sandy Hook and Orlando Pulse. If it is true, then like I said a man that has participated in DHS/FEMA Capstone Drills (he snuck a camera in during an orientation on how to be a crisis actor) himself from Texas on YouTube called Side Thron who is offering up $100,000 to prove any of these shootings are authentic. That money could well spent helping the victims and Read more ». Certainly a False Flag, but people died. When every single False Flag is claimed to not take any lives, it goes against the whole point of a False Flag.

People HAVE to really die in order for the public to beg for their government to “do something” and their government is more than happy to oblige since they (or more likely the D e e P S t a t e ) created the attack all along to force people to ask to have more of their rights taken away. Look at 9/11. The world prior to 9/11 and after 9/11 are two vastly different realities.

I feel bad for teens today who have no idea what it was like to live without TSA or being fondled before you fly. I remember being able to take a Birthday cake on an airplane, set it on my lap and fly from Read more ». Its noteworthy that this shooting happened the same day as the Paradise Papers leak which is getting Very little, if any mainstream media coverage. This leak is huge. It over 13 million digital documents that track down 10 Trillion Dollars in off shore investments made by HUGe corporations like Apple, Facebook to the Queen of England also includes Celebrities and politicians All avoiding taxation. How convienent that this story is being overshadowed. My heart goes out!

What a tangled web! And unnecessary loss of life. Firstly, yes this is horrible, but it is also out of our control. I have accepted that for whatever reason I was born/created on this planet with a very limited scope. I cannot read minds. I cannot see the future.

And I can reasonably assume that I was meant to be this way or I would not be limited. My heart breaks for those around me carrying a much larger load of responsibility and anxiety than they need or were designed to. If you can’t see the bigger picture that’s probably a sign you shouldn’t feel obligated to try to “fix” it. What we do control is our own actions and response. We do not have to be overwhelmed or fearful.

We do not have to feed into the negative atmosphere of helplessness and defeat. And hey who knowsmaybe there is someone who can see the bigger picture that we Read more ».

And to also mention: The Adjustment to being under surveillance when in public, as the government has to prevent anyone walking down the road carrying a conceiled weapon from using it.? That means scanportals and smartcamera’s everywhere you will walk society’s streets.

Passportchip-readers and irisscans are under construction (well, they say). Every place that is open for public will have to be controlled for safety purposes. And yet, somehow I do not think I will feel safer this way.

So I too am keeping talking about the bigger links between those plans, and pointing out the absurdity of those half-measurements that only effect the good ones, instead of the bad ones, if you catch my drift. It works in numbing people to a submissive passive state where they only sit and wait,because there seems no other way? Some take time to read, talk, think, react and others sit and pray, mostly with eyes closed. Some others try to make adjustments in taking care of their offspring like it should outlive the parents, some parents take their children for grantuit on the same level as watching a war on cnn.

I do not know what works best for you, but there comes a time you have to decide for yourself. MK ultra and the dark side of mass media broadcasting everything that the Illuminati has which glorifies death to the highest degree with regards to depopulation where the strong rise above the weak and the vulnerable. The elite would do anything to “trigger” a perfectly normal person to go out on a shooting spree as a buildup to what they’re really after. The signs and symbols written everywhere even frighteningly foretelling the demise of a couple of innocent people is a sad reality these days. This is why I don’t buy into today’s crap unlike most sheeple of today who are quite oblivious to being under surveillance by the powers-that-be. Even random people in the military could be easy targets for “triggers” and unwittingly find themselves becoming MK ultra victims carrying out the bidding of the elite which is something thats not new at the moment but yet very popular Read more ». Veteranstoday.com with Kevin Barret’s articles explains that allot of this synthetic terror is derived from not only MKULTRA but, the GLADIO techniques that were used in Europe tp terrorize European nations in the 50’s, 60’s and 70’s.

TPTB use the same tried and true methods over and over again but, it is all becoming painfully obvious that these aren’t random acts of individuals.These are systems where CIA/FBI in conjunction with local governments are enacting these atrocities on our dime and it goes all the way up to the usuary Banksters aka as the Rothchilds and all of their “institutions”. ((( ))) is used by anti-semites and nazis to discretely identify jewish individuals online. Please keep that s**t out of here. There is so much anti-semitism in these conspiracy theory circles and it really takes away from the credibility of the theories because people think we’re all just anti-semites and homophobes and whatnot. This is not and never has been about race/ religion/ sexuality/ etc.

This is about the rich and powerful, regardless of the aforementioned categories, abusing their power and f*****g up our world. Being jewish does not automatically mean being evil, corrupt, or disingenuous. NO category of race, religion, or what have you automatically equals those things. It also IS religiously motivated. The perpetrators behind all these things are satanists, and are entirely serious about their rituals and beliefs, by the looks of it. Also, Rothschild ‘Judaism’ (Kabbalah and Talmud) is clearly involved. In short, essentially everything SEA1111444 said above is false.

Everything happening was foreseen to happen by the 2000 year old Bible. As for the German nazis, it’s no longer clear to me what really happened during those years. We’ve been lied to about what WW2 was really about and what actually happened, that’s for sure. I always appreciate these eye opening articles.

However, VC, I believe it is time for you and your audience to publicly investigate exactly WHO is behind these programming entertainment vehicles – who is responsible for the financing, the script, the production, the set design – we need to name names and start asking these people very specific questions such as – how was it decided that this scene would look like this? If it i was the writer or director, were they told to portray it this way? Same with all the music videos – we need to find out exactly who is involved in the production of these mass programming vehicles and start asking questions, and follow the money as well. All the stuff happening in Texas is to push folks to get more gun control silly sheep forget that a gun is an OBJECT, and takes a PERSON to pull the trigger. This person almost certainly was on pharmaceuticals of some type, and in fact, MOST shooters lately seem to be taking the kind that has severe suicidal and violent side effects. Mkultra and other brainwashing techniques are probably also involved; it seems to be that either it’s gaining a foothold and is becoming more common and ‘out’ so to speak, or these guys had triggers embedded long ago and are just now ‘going off’, for whatever reason.

Almost all the acts of ‘terror’ are to push legislation their way and to disarm the people. Even Texas’ own Senator Cornyn is suddenly pushing for the legislation to have more gun control since the shooting. This week was a voting week Read more ». Notice how many times these massacres have occurred in small churches in recent years – never in a synagogue or a mosque, yet all we hear is Islamophobia this, Antisemitism that.

Yet no body points this trend out – certainly not in the utterly compromised/controlled media. We’re being terrorised in plain open sight, being butchered in our streets, having our children raped and abused in their thousands (the perps protected by police and social services) – whether by Jewish elites or muslim gangs. Our meat is ritually slaughtered halal or kosher, unlabelled as such, and we buy it without knowing. The same is true of halal and kosher certified brands of cosmetics and packet food – we pay for these companies to certify their brands! The list is endless. The attack on our society is real and (((those))) responsible must be held to account. There *was* an attack on a mosque in Canada a year or two ago.

In Ottawa, if I’m not mistaken, or possibly in Quebec. I know there seems to be a lot of hate on Muslims in Ottawa; white folk feel they’re taking over and forcing Islamic beliefs on others. Idk how true the “takeover” is, just as I wonder if (if there is valid reasons for the Islamaphobia there) it’s the “bad seed Muslims”. There’s wingnuts of every faith who make the rest look bad.

Anyways, yes there was an attack on a mosque ages ago. We heard a bit about it for a week, then it was swept under the rug cuz Islamaphobia. Thy Unveiling – you’re suggesting there’s an irrational fear of islam and mass immigration? Maybe where you live there’s no sign of mass muslim immigration. Here in the UK, the effects of mass immigration is astonishing, the demographic of every town, village and city has completely transformed within a very short time frame. I myself as a white man have regularly been subjected to racist harassment/intimidation. My ex-girlfriend started dating a muslim who literally treated her like a slave.

But you’ve managed to find one instance of an attack on a mosque (the details of which are vague) so that evens everything out apparently. You want proof of a deliberate take-over – the UN themselves decided it would happen around 20 years ago – no coincidence that this is the same time mass immigration started. Are you kidding? These are warnings in the form of entertainment. Movies and TV shows, etc, are NOTICES.

This is no coincidence. The controllers have ALL of this planned. If not, they can go back into time and manipulate events. It’s called Predictive Programming. Just like the author of a book knows how it ends so throws in some foreshadowing for the reader to think he or she is smart to pick up on it. But to think one smart for picking up on foreshadowing is a jokebecause it’s a fait accompli.

It’s already happened. Look at the CA fires recently and see the movie GeoStorm. One point of reference for what we are experiencing and what we’ll see to its fruition is what General Albert Pike wrote regarding the “Three World Wars”. We are in the phase of the plan of the 3rd World war. This 3rd World War will be the final world war to usher in the Anti-Christ, the doctrine of Lucifer being finally externalized to the masses (ie, Lucifer is god).

That’s why “they” are bringing out into the open that which was previously hidden (occult), by means of the music industry, news, television, art, et cetera. The solution to our problems starts with prayer, prayer, prayer.Pray for God to open you heart/soul to truly see this life in the eyes of faith, hope, and LOVE. Prayer (persistent, frequent, complete surrender) is the key to God. Seek, knock, persistently ask. Pray, hope and don’t worry.

God will guide those who stay faithful and true during these Apocalyptic times foretold in St John’s book of Revelations. Sin is insanity, and the times are now quite insane, so it can’t be much longer before the King of Kings returns to administer His Justice. The sheep and the goats are being separated in these times.

Don’t listen to those who call us “sheeple” – I would be overjoyed to be considered a sheep, and I know my Shepherd, my Saviour, my God, my King. The scoffers will be sorrowful when the Truth is revealed. Pray for them too.

I WISH Kingsman: The Secret Service was a foreshadowing of actual things to come. How I would love to see all the elite scumbags and corrupt world leaders have all their heads blown up with a single button press (yes, single button press, all those implants were activated at once, they only appeared to blow up separately, to enchance the hilarity of that sequence).

And that was one of the best scenes in movie history, because even though he was mind-controlled, he didn’t kill innocent people, he killed a hate group. That “church” was a parody of the Westboro Baptist Church, and a lot of people would love to see that cancer get snuffed out in a long, dragged-out, extremely gory scene with rock music playing in the background. Finally, all those things he said right before the chips were activated, he said all of that ironically, because he Read more ». 9000 babies have been slaughtered in the womb in America since the 26 were slaughtered 3 days ago. That does not in any way detract from the murder of the 26, but it adds to them. This is something for you to ponder, to put things in perspective. Maybe it can help you understand why God would allow this to happen, when we ourselves allow the murder of the innocent every single day.

Should God help us? Should God bless us?

Does God owe us something? Should we be surprised by what’s on TV? Should we be surprised by Marilyn Manson? Idk about you, but I am blessed every single day. I would never allow the murder of anyone innocent, child or otherwise, if I could help it – that said, I am only one person. God doesn’t owe me anything, but He helps, regardless.

Not because of who I am, but because of the fact that He loves me. It’s not God that allowed this to happen; its people who allowed it to happen and the stupid laws that make it almost impossible to defend ourselves against those who would destroy us for the simple reason that we believe in Him.

No, there is no surprise for folks like Manson or the crazy who killed those in Texas, either. There is just sadness for those who let themselves be slaughtered. Thank God for the one who was there who DID have protection, or the whole church would have been killed. ENOUGH WITH THE FALSE FLAG CRAP.

These attacks are being carried out by very real, very disturbed individuals, and it points to a systemic societal problem, not some crackpot conspiracy by government/Jews/Muslims/flavor of the day. If you want to play with alternate fiction and intrigue, NaNoWriMo is going on. Otherwise, stop mocking the deaths of innocents by questioning their existence, stop disrespecting the mourning families of the victims with your need to see ghosts where there are none, stop dismissing the very real criminal justice and bureaucracy failing that lead to this terrible event, and stop feeding your paranoia by sequestering yourselves in communities that refuse to critically think about the plausibility of all of these twisted stories woven around tragedies. Instead of tsking about the downfall of humanity and looking for eyes and crosses and triangles everywhere, get out into the world, meet these people that you’ve vilified and Read more ». Ordinarily I come to this site because the articles are usually good in terms of highlighting masonic control in elite circles.

However, the community here is just ridiculous. My girlfriend was friends with one of the victims killed (yes – he was killed) in the Manchester Arena bombing.

I came here soon after to see loads of posts laughing about “actors”, suggesting the whole thing was a hoax. OK – so where did this guy disappear? Who paid for that funeral? It wouldn’t surprise me to see someone here denying the gulags existed, and that millions of people died in them. Most of us are not sequestered, but functioning members of society.

Maybe if you don’t want to be labeled a plant, you should not label us as crackpot conspiracy theorists, either. Most of us have our eyes open – how about you? This shooting (and many others besides) are just too conveniently spaced to political and social events happening around the world for them to all be ‘coincidental’. How many ‘coincidences’ do you need to see line up before you connect the dots and realize something is actually going on? Like: At the time of this shooting, there were preparations to vote in Texas on state constitutional amendments on the 7th. Early voting was going on. At the time of this shooting, there was the release of the Paradise Paper leaks.

There is probably more, you have to look around yourself and see. Jesusknight – I believe that the shootings happen, but where I differ from the OP, I believe that many of them are conspired by elites. But when you see people constantly mocking these attacks, saying they’re fake – that’s where the line must be drawn. I know fake attacks were acted out in Syria and probably other wars -thousands of miles away- but you couldn’t get away with that in America/Europe. Every victim is known to someone.

If there are fake terrorist attacks, they’ll be few and far between.