Caffeine is a

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(CNS)

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

of the methylxanthine

class Class, Classes, or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used d ...

and is the most commonly consumed psychoactive substance globally. It is mainly used for its eugeroic (

wakefulness Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, ...

promoting), ergogenic (physical performance-enhancing), or nootropic (cognitive-enhancing) properties. Caffeine acts by blocking the binding of

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside build ...

at a number of

adenosine receptor The adenosine receptors (or P1 receptors) are a class of Purinergic receptor, purinergic G protein-coupled receptors with adenosine as the endogenous ligand (biochemistry), ligand. There are four known types of adenosine receptors in humans: Aden ...

types, inhibiting the centrally

depressant Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various ...

effects of adenosine and enhancing the release of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

. Caffeine has a three-dimensional structure similar to that of adenosine, which allows it to bind and block its receptors. Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase, increases calcium release from intracellular stores, and antagonizes GABA receptors, although these mechanisms typically occur at concentrations beyond usual human consumption. Caffeine is a bitter, white crystalline purine, a methylxanthine

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

, and is chemically related to the

adenine Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is ...

and

guanine Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...

bases of deoxyribonucleic acid (DNA) and

ribonucleic acid Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins ( messenger RNA). RNA and deoxyr ...

(RNA). It is found in the seeds, fruits, nuts, or leaves of a number of plants native to Africa, East Asia, and South America and helps to protect them against herbivores and from competition by preventing the germination of nearby seeds, as well as encouraging consumption by select animals such as honey bees. The most common sources of caffeine for human consumption are the tea leaves of the '' Camellia sinensis'' plant and the coffee bean, the seed of the '' Coffea'' plant. Some people drink

beverages A drink or beverage is a liquid intended for human consumption. In addition to their basic function of satisfying thirst, drinks play important roles in human culture. Common types of drinks include plain drinking water, milk, juice, smoothie ...

containing caffeine to relieve or prevent drowsiness and to improve cognitive performance. To make these drinks, caffeine is extracted by

steeping Steeping is the soaking of an organic solid, such as leaves, in a liquid (usually water) to extract flavours or to soften it. The specific process of teas being prepared for drinking by leaving the leaves in heated water to release the flavour ...

the plant product in water, a process called infusion. Caffeine-containing drinks, such as tea,

coffee Coffee is a beverage brewed from roasted, ground coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content, but decaffeinated coffee is also commercially a ...

, and

cola Cola is a Carbonation, carbonated soft drink flavored with vanilla, cinnamon, citrus essential oil, oils, and other flavorings. Cola became popular worldwide after the American pharmacist John Stith Pemberton invented Coca-Cola, a trademarked br ...

, are consumed globally in high volumes. In 2020, almost 10 million tonnes of coffee beans were consumed globally. Caffeine is the world's most widely consumed

psychoactive drug A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

. Unlike most other psychoactive substances, caffeine remains largely unregulated and legal in nearly all parts of the world. Caffeine is also an outlier as its use is seen as socially acceptable in most cultures and is encouraged in some. Caffeine has both positive and negative health effects. It can treat and prevent the premature infant breathing disorders bronchopulmonary dysplasia of prematurity and apnea of prematurity. Caffeine citrate is on the

WHO Model List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It may confer a modest protective effect against some diseases, including

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

. Some people experience sleep disruption 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 drug dependence – associated with withdrawal symptoms such as sleepiness, headache, and irritability – when an individual stops using caffeine after repeated daily intake. Tolerance to the autonomic effects of increased blood pressure, heart rate, and 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 U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) as

generally recognized as safe Generally recognized as safe (GRAS) is a United States Food and Drug Administration (FDA) designation that a chemical or substance added to food is considered safe by experts under the conditions of its intended use. An ingredient with a GRAS d ...

. Toxic doses, over 10 grams per day for an adult, greatly exceed the typical dose of under 500 milligrams per day. The European Food Safety Authority reported that up to 400 mg of caffeine per day (around 5.7 mg/kg of body mass per day) does not raise safety concerns for non-pregnant adults, while intakes up to 200 mg per day for pregnant and lactating women do not raise safety concerns for the fetus or the breast-fed infants. A cup of coffee contains 80–175 mg of caffeine, depending on what "bean" (seed) is used, how it is roasted, and how it is prepared (e.g., drip,

percolation In physics, chemistry, and materials science, percolation () refers to the movement and filtration, filtering of fluids through porous materials. It is described by Darcy's law. Broader applications have since been developed that cover connecti ...

, or

espresso Espresso (, ) is a concentrated form of coffee produced by forcing hot water under high pressure through finely ground coffee beans. Originating in Italy, espresso has become one of the most popular coffee-brewing methods worldwide. It is cha ...

). Thus roughly 50–100 ordinary cups of coffee would be required to reach the toxic dose. However, pure powdered caffeine, which is available as a

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

, can be lethal in tablespoon-sized amounts.

Uses

Medical

Caffeine is used for both prevention and treatment of bronchopulmonary dysplasia in premature infants. It may improve weight gain during therapy and reduce the incidence of

cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, spasticity, stiff muscles, Paresis, weak muscles, and tremors. There may b ...

as well as reduce language and cognitive delay. On the other hand, subtle long-term side effects are possible. Caffeine is used as a primary treatment for apnea of prematurity, but not prevention. It is also used for orthostatic hypotension treatment. Some people use caffeine-containing beverages such as coffee or tea to try to treat their

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

. Evidence to support this practice is poor. It appears that caffeine in low doses improves airway function in people with asthma, increasing forced expiratory volume (FEV1) by 5% to 18% for up to four hours. The addition of caffeine (100–130 mg) to commonly prescribed pain relievers such as

paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

modestly improves the proportion of people who achieve pain relief. Consumption of caffeine after abdominal surgery shortens the time to recovery of normal bowel function and shortens length of hospital stay. Caffeine was formerly used as a second-line treatment for ADHD. It is considered less effective than

methylphenidate Methylphenidate, sold under the brand names Ritalin ( ) and Concerta ( ) among others, is a central nervous system (CNS) stimulant used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It may be taken Oral adm ...

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

but more so than placebo for children with ADHD. Children, adolescents, and adults with ADHD are more likely to consume caffeine, perhaps as a form of self-medication.

Enhancing performance

Cognitive performance

Caffeine is a

stimulant that may reduce

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

and drowsiness. At normal doses, caffeine has variable effects on learning and memory, but it generally improves reaction time,

, concentration, and

motor coordination In physiology, motor coordination is the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. This coordination is achieved by adjusting kinematic and kinetic parameters associated with each bo ...

. 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

sleep Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain Sensory nervous system, sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with th ...

and improves task performance during sleep deprivation. Shift workers who use caffeine make fewer mistakes that could result from drowsiness. Caffeine in a dose dependent manner increases alertness in both fatigued and normal individuals. A

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...

and

meta-analysis Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...

from 2014 found that concurrent caffeine and -theanine use has synergistic psychoactive effects that promote alertness, attention, and task switching; these effects are most pronounced during the first hour post-dose.

Physical performance

Caffeine is a proven ergogenic aid in humans. Caffeine improves athletic performance in aerobic (especially endurance sports) and anaerobic conditions. Quote: 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

muscle fatigue Muscle fatigue is when muscles that were initially generating a normal amount of force, then experience a declining ability to generate force. It can be a result of vigorous exercise, but abnormal fatigue may be caused by barriers to or interfer ...

and central fatigue), and cycling power output. Caffeine increases

basal metabolic rate Basal metabolic rate (BMR) is the rate of energy expenditure per unit time by endothermic animals at rest.. In other words it is the energy required by body organs to perform normal It is reported in energy units per unit time ranging from watt ( ...

in adults. Caffeine ingestion prior to aerobic exercise increases fat oxidation, particularly in persons with low physical fitness. 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

Adults

For the general population of healthy adults,

Health Canada Health Canada (HC; )Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary units, department of the Gove ...

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.

Children

In healthy children, moderate caffeine intake under 400 mg produces effects that are "modest and typically innocuous". As early as six months old, infants can metabolize caffeine at the same rate as that of adults. 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. The

American Academy of Pediatrics The American Academy of Pediatrics (AAP) is the largest professional association of pediatricians in the United States. It is headquartered in Itasca, Illinois, and maintains an office in Washington, D.C. The AAP has published hundreds of poli ...

recommends that caffeine consumption, particularly in the case of energy and sports drinks, 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, Centers for Disease Control & Prevention,

, Sports Medicine & Fitness committee, National Federations of High School Associations). For children age 12 and under,

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:

Adolescents

Health Canada has not developed advice for adolescents because of insufficient data. However, they suggest that daily caffeine intake for this age group be no more than 2.5 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 experiencing adverse effects.

Pregnancy and breastfeeding

The metabolism of caffeine is reduced in pregnancy, especially in the third trimester, and the half-life of caffeine during pregnancy can be increased up to 15 hours (as compared to 2.5 to 4.5 hours in non-pregnant adults). 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 Food Standards Agency 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 American Congress of Obstetricians and Gynecologists (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) . 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 congenital malformations,

miscarriage Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...

or growth retardation 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 low birth weight 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

Effects of moderate caffeine consumption

Physiological

Caffeine in coffee and other caffeinated drinks can affect gastrointestinal motility and

gastric acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other a ...

secretion. In postmenopausal women, high caffeine consumption can accelerate bone loss. Caffeine, alongside other factors such as stress and fatigue, can also increase the pressure in various muscles, including the eyelids. Acute ingestion of caffeine in large doses (at least 250–300 mg, equivalent to the amount found in 2–3 or 5–8 ) 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 diuresis (increase in water excretion) and a

natriuresis Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by Brain natriuretic peptide, ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldost ...

(increase in saline excretion); it is mediated via proximal tubular adenosine receptor blockade. The acute increase in urinary output may increase the risk of

dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

. However, chronic users of caffeine develop a tolerance 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 anxiety disorders. According to a 2011 literature review, caffeine use may induce anxiety and panic disorders in people with

. 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 depression and lower

suicide Suicide is the act of intentionally causing one's own death. Risk factors for suicide include mental disorders, physical disorders, and substance abuse. Some suicides are impulsive acts driven by stress (such as from financial or ac ...

risk. Two reviews indicate that increased consumption of coffee and caffeine may reduce the risk of depression. Some textbooks state that caffeine is a mild euphoriant, while others state that it is not a euphoriant. Caffeine-induced anxiety disorder is a subclass of the

DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiat ...

diagnosis of substance/medication-induced anxiety disorder.

Reinforcement disorders

Addiction

Whether caffeine can result in an addictive disorder depends on how addiction is defined. Compulsive caffeine consumption under any circumstances has not been observed, and caffeine is therefore not generally considered addictive. Some diagnostic sources, such as the and

ICD-10 ICD-10 is the 10th revision of the International Classification of Diseases (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social cir ...

, 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

American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 39,200 members who are in ...

's does not include the diagnosis of a ''caffeine addiction'' but proposes criteria for the disorder for more study.

Dependence and withdrawal

Caffeine withdrawal 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. and most cases of caffeine withdrawal were 13% in the moderate sense. Moderately

physical dependence Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certa ...

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 psychological dependence 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, depressed mood/ irritability, flu-like symptoms,

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, and

. Additionally, the signs and symptoms must disrupt important areas of functioning and are not associated with effects of another condition. The ICD-11 includes caffeine dependence 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 APA, 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

clinical significance In medicine and psychology, clinical significance is the practical importance of a treatment effect—whether it has a real genuine, palpable, noticeable effect on daily life. Types of significance Statistical significance Statistical significanc ...

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". Tolerance to the effects of caffeine occurs for caffeine-induced elevations in

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

and the subjective feelings of nervousness though the effects are not drastic. Sensitization, the process whereby effects become more prominent with use, may occur for positive effects such as feelings of alertness and wellbeing. 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 cup of coffee or two to three 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

A neuroprotective effect of caffeine against

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

and dementia is possible but the evidence is inconclusive. Caffeine may lessen the severity of acute mountain sickness 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

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

. Regular caffeine consumption may reduce the risk of developing

and may slow the progression of Parkinson's disease. Caffeine increases intraocular pressure in those with

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

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".

Energy crash

Caffeine is reputed to cause a fall in energy several hours after drinking, but this is not well researched.

Overdose

Consumption of per day is associated with a condition known as '' caffeinism.'' Caffeinism usually combines caffeine dependency with a wide range of unpleasant symptoms including nervousness, irritability, restlessness,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

, headaches, and palpitations after caffeine use. Caffeine overdose can result in a state of central nervous system overstimulation 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, gastrointestinal disturbance, muscle twitching, rambling flow of thought and speech,

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

or cardiac arrhythmia, periods of inexhaustibility, and psychomotor agitation. According to the International Classification of Diseases (ICD-11), cases of very high caffeine intake (e.g. > 5 g) may result in caffeine intoxication with symptoms including mania, depression, lapses in judgment, disorientation, disinhibition, delusions, hallucinations or psychosis, and rhabdomyolysis.

Energy drinks

High caffeine consumption in energy drinks (at least one liter or 320 mg of caffeine) was associated with short-term cardiovascular side effects including hypertension, prolonged QT interval, and heart palpitations. These cardiovascular side effects were not seen with smaller amounts of caffeine consumption in energy drinks (less than 200 mg).

Severe intoxication

there is no known antidote or reversal agent for caffeine intoxication. Treatment of mild caffeine intoxication is directed toward symptom relief; severe intoxication may require peritoneal dialysis,

hemodialysis Hemodialysis, American and British English spelling differences#ae and oe, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of Kidney dialys ...

, or hemofiltration. Intralipid infusion therapy is indicated in cases of imminent risk of cardiac arrest in order to scavenge the free serum caffeine.

Lethal dose

Death from caffeine ingestion appears to be rare, and most commonly caused by an intentional overdose of medications. In 2016, 3702 caffeine-related exposures were reported to Poison Control Centers in the United States, of which 846 required treatment at a medical facility, and 16 had a major outcome; and several caffeine-related deaths are reported in case studies. The LD₅₀ of caffeine in rats is 192 milligrams per kilogram of body mass. The fatal dose in humans is estimated to be 150–200 milligrams per kilogram, which is 10.5–14 grams for a typical adult, equivalent to about 75–100 . There are cases where doses as low as 57 milligrams per kilogram have been 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 2013 of a man with liver cirrhosis who overdosed on caffeinated mints.

Interactions

Caffeine is a substrate for CYP1A2, and interacts with many substances through this and other mechanisms.

Alcohol

According to DSST,

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

causes a decrease in performance on their standardized tests, and caffeine causes a significant improvement. When alcohol and caffeine are consumed jointly, the effects of the caffeine are changed, but the alcohol effects remain the same. For example, consuming additional caffeine does not reduce the effect of alcohol. 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 effect of alcohol on the activational aspect of behavioral control, but has no effect on the inhibitory behavioral control. The Dietary Guidelines for Americans recommend avoidance of concomitant consumption of alcohol and caffeine, as taking them together may lead to increased alcohol consumption, with a higher risk of alcohol-associated injury.

Smoking

Smoking tobacco has been shown to increase caffeine clearance by 56% as a result of polycyclic aromatic hydrocarbons inducing the CYP1A2 enzyme. The CYP1A2 enzyme that is induced by smoking is responsible for the metabolism of caffeine; increased enzyme activity leads to increased caffeine clearance, and is associated with greater coffee consumption for regular smokers.

Birth control

Birth control pills can extend the half-life of caffeine by as much as 40%, requiring greater attention to caffeine consumption.

Medications

Caffeine sometimes increases the effectiveness of some medications, such as those for headaches. Caffeine was determined to increase the potency of some over-the-counter

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

medications by 40%. The pharmacological effects of adenosine may be blunted in individuals taking large quantities of methylxanthines like caffeine. Some other examples of methylxanthines include the medications theophylline and aminophylline, which are prescribed to relieve symptoms of asthma or COPD.

Pharmacology

Pharmacodynamics

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 adenosine accumulates in the neuronal

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

, in turn binding to and activating

s found on certain CNS neurons; when activated, these receptors produce a cellular response that ultimately increases drowsiness. When caffeine is consumed, it antagonizes adenosine receptors; in other words, caffeine prevents adenosine from activating the receptor by blocking the location on the receptor where adenosine binds to it. As a result, caffeine temporarily prevents or relieves drowsiness, and thus maintains or restores alertness.

Receptor and ion channel targets

Caffeine is an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.adenosine A_2A receptors, and knockout mouse studies have specifically implicated antagonism of the A_2A receptor as responsible for the wakefulness-promoting effects of caffeine. Antagonism of A_2A receptors in the ventrolateral preoptic area (VLPO) reduces inhibitory GABA neurotransmission to the tuberomammillary nucleus, a

histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...

rgic 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 ( A₁, A_2A, A_2B, and A₃), although with varying potencies. The

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

( K_D) values of caffeine for the human adenosine receptors are 12 μM at A₁, 2.4 μM at A_2A, 13 μM at A_2B, and 80 μM at A₃. Antagonism of adenosine receptors by caffeine also stimulates the medullary vagal, vasomotor, and

respiratory center The respiratory center is located in the medulla oblongata and pons, in the brainstem. The respiratory center is made up of three major respiratory groups of neurons, two in the medulla and one in the pons. In the medulla they are the dorsal ...

s, which increases respiratory rate, reduces heart rate, and constricts blood vessels. Adenosine receptor antagonism also promotes

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

release (e.g., monoamines and

), which endows caffeine with its stimulant effects;

acts as an inhibitory neurotransmitter that suppresses activity in the central nervous system. Heart palpitations are caused by blockade of the A₁ receptor. Because caffeine is both water- and lipid-soluble, it readily crosses the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

that separates the bloodstream from the interior of the brain. Once in the brain, the principal mode of action is as a nonselective

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.competitive antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

. In addition to its activity at adenosine receptors, caffeine is an inositol trisphosphate receptor 1 antagonist and a voltage-independent activator of the ryanodine receptors ( RYR1, RYR2, and RYR3). It is also a competitive antagonist of the ionotropic glycine receptor.

Effects on striatal dopamine

While caffeine does not directly bind to any dopamine receptors, it influences the binding activity of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

at its receptors in the

striatum The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...

by binding to adenosine receptors that have formed GPCR heteromers with dopamine receptors, specifically the A₁– D₁ receptor heterodimer (this is a receptor complex with one adenosine A₁ receptor and one dopamine D₁ receptor) and the A_2A– D₂ receptor heterotetramer (this is a receptor complex with two adenosine A_2A receptors and two dopamine D₂ receptors). The A_2A–D₂ 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 dorsal striatum and nucleus accumbens core (a substructure within the ventral striatum), but not the nucleus accumbens shell, by antagonizing A₁ receptors in the axon terminal of dopamine neurons and A₁– A_2A heterodimers (a receptor complex composed of one adenosine A₁ receptor and one 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 drug tolerance.

Enzyme targets

Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor. As a competitive nonselective phosphodiesterase inhibitor, caffeine raises intracellular cyclic AMP, activates protein kinase A, inhibits TNF-alpha and

leukotriene Leukotrienes are a family of eicosanoid inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...

synthesis, and reduces inflammation and innate immunity. Caffeine also affects the cholinergic system where it is a moderate inhibitor of the enzyme acetylcholinesterase.

Pharmacokinetics

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 by first-order kinetics. Caffeine can also be absorbed rectally, evidenced by suppositories of ergotamine tartrate and caffeine (for the relief of migraine) and of chlorobutanol and caffeine (for the treatment of hyperemesis). However, rectal absorption is less efficient than oral: the maximum concentration ( C_max) and total amount absorbed ( AUC) are both about 30% (i.e., 1/3.5) of the oral amounts. Caffeine's

biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

– 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, liver enzyme function level (needed for caffeine metabolism) and age. In healthy adults, caffeine's half-life is between 3 and 7 hours. The half-life is decreased by 30-50% in adult male smokers, approximately doubled in women taking oral contraceptives, and prolonged in the last trimester of pregnancy. In newborns the half-life can be 80 hours or more, dropping rapidly with age, possibly to less than the adult value by age 6 months. The antidepressant fluvoxamine (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 metabolized in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

by the

cytochrome P450 oxidase Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherich ...

enzyme system (particularly by the CYP1A2 isozyme) into three dimethyl xanthines, each of which has its own effects on the body: * Paraxanthine (84%): Increases lipolysis, leading to elevated

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

and free

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

levels in

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

. * Theobromine (12%): Dilates

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s and increases

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

volume. Theobromine is also the principal

in the

cocoa bean The cocoa bean, also known as cocoa () or cacao (), is the dried and fully fermented seed of ''Theobroma cacao'', the cacao tree, from which cocoa solids (a mixture of nonfat substances) and cocoa butter (the fat) can be extracted. Cacao tree ...

(

chocolate Chocolate is a food made from roasted and ground cocoa beans that can be a liquid, solid, or paste, either by itself or to flavoring, flavor other foods. Cocoa beans are the processed seeds of the cacao tree (''Theobroma cacao''); unprocesse ...

). * Theophylline (4%): Relaxes

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

s of the bronchi, and is used to treat

. The therapeutic dose of theophylline, however, is many times greater than the levels attained from caffeine metabolism. 1,3,7-Trimethyluric acid is a minor caffeine metabolite. 7-Methylxanthine is also a metabolite of caffeine. Each of the above metabolites is further metabolized and then excreted in the urine. Caffeine can accumulate in individuals with severe

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

, 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

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

on both chromosomes 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 anhydrous 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 quickly 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

conjugate acid A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the rever ...

= ~0.6) requiring strong acid to protonate it.This is the pK_a for protonated caffeine, given as a range of values included in Caffeine does not contain any stereogenic centers and hence is classified as an achiral molecule. The xanthine core of caffeine contains two fused rings, a pyrimidinedione and imidazole. The pyrimidinedione in turn contains two

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

functional groups that exist predominantly in a

zwitterion In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively and negatively charged functional groups. : (1,2- dipolar compounds, such as ylides, are sometimes excluded from ...

resonance Resonance is a phenomenon that occurs when an object or system is subjected to an external force or vibration whose frequency matches a resonant frequency (or resonance frequency) of the system, defined as a frequency that generates a maximu ...

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 sp² hybridized and planar. The imidazole ring also has a

. Therefore, the fused 5,6 ring core of caffeine contains a total of ten pi electrons and hence according to Hückel's rule is

aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...

Synthesis

The

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

of caffeine is an example of

convergent evolution Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last comm ...

among different species. Caffeine may be synthesized in the lab starting with 1,3-dimethylurea and malonic acid. Production of synthesized caffeine largely takes place in pharmaceutical plants in China. Synthetic and natural caffeine are chemically identical and nearly indistinguishable. The primary distinction is that synthetic caffeine is manufactured from urea and chloroacetic acid, while natural caffeine is extracted from plant sources, a process known as decaffeination. Despite the different production methods, the final product and its effects on the body are identical. Research on synthetic caffeine supports that it has the same stimulating effects on the body as natural caffeine. And although many claim that natural caffeine is absorbed slower and therefore leads to a gentler caffeine crash, there is little scientific evidence supporting the notion.

Decaffeination

Germany, the birthplace of decaffeinated coffee, is home to several decaffeination plants, including the world's largest, Coffein Compagnie. Over half of the decaf coffee sold in the U.S. first travels from the tropics to Germany for caffeine removal before making its way to American consumers. Extraction of caffeine from coffee, to produce caffeine and decaffeinated coffee, can be performed using various solvents. Following are 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 activated charcoal, 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: Supercritical carbon dioxide is an excellent nonpolar

solvent A solvent (from the Latin language, Latin ''wikt:solvo#Latin, solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a Solution (chemistry), solution. A solvent is usually a liquid but can also be a solid, a gas ...

for caffeine, and is safer than the organic solvents that are otherwise used. The extraction process is simple: is forced through the green coffee beans at temperatures above 31.1 °C and pressures above 73 atm. Under these conditions, is in a " supercritical"

state State most commonly refers to: * State (polity), a centralized political organization that regulates law and society within a territory **Sovereign state, a sovereign polity in international law, commonly referred to as a country **Nation state, 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 is then sprayed with high-pressure water to remove the caffeine. The caffeine can then be isolated by charcoal adsorption (as above) or by distillation, recrystallization, or

reverse osmosis Reverse osmosis (RO) is a water purification process that uses a partially permeable membrane, semi-permeable membrane to separate water molecules from other substances. RO applies pressure to overcome osmotic pressure that favors even distribu ...

. * Extraction by organic solvents: Certain organic solvents such as ethyl acetate 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 xanthines DMPX and 8-chlorotheophylline, which is an ingredient in dramamine. Members of a class of nitrogen substituted xanthines are often proposed as potential alternatives to caffeine. Many other xanthine analogues constituting the adenosine receptor antagonist class have also been elucidated. Some other caffeine analogs: * Dipropylcyclopentylxanthine * 8-Cyclopentyl-1,3-dimethylxanthine * 8-Phenyltheophylline

Precipitation of tannins

Caffeine, as do other alkaloids such as

cinchonine Cinchonine is an alkaloid found in ''Cinchona officinalis''. It is used in asymmetric synthesis in organic chemistry. It is a stereoisomer and pseudo-enantiomer of cinchonidine. It is structurally similar to quinine, an antimalarial drug. It i ...

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg ...

strychnine Strychnine (, , American English, US chiefly ) is a highly toxicity, toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, ...

, precipitates polyphenols and

tannin Tannins (or tannoids) are a class of astringent, polyphenolic biomolecules that bind to and Precipitation (chemistry), precipitate proteins and various other organic compounds including amino acids and alkaloids. The term ''tannin'' is widel ...

s. This property can be used in a quantitation method.

Natural occurrence

Around thirty plant species are known to contain caffeine. Common sources are the "beans" (seeds) of the two cultivated coffee plants, ''

Coffea arabica ''Coffea arabica'' (), also known as the Arabica coffee, is a species of flowering plant in the coffee and madder family Rubiaceae. It is believed to be the first species of coffee to have been cultivated and is the dominant cultivar, represe ...

'' and ''

Coffea canephora ''Coffea canephora'' (especially ''C. canephora var. robusta'', so predominantly cultivated that it is often simply termed ''Coffea robusta'', or commonly robusta coffee) is a species of coffee plant that has its origins in central and weste ...

'' (the quantity varies, but 1.3% is a typical value); and of the cocoa plant, ''

Theobroma cacao ''Theobroma cacao'' (cacao tree or cocoa tree) is a small ( tall) evergreen tree in the Malvaceae family. Its seedscocoa beansare used to make chocolate liquor, cocoa solids, cocoa butter and chocolate. Although the tree is native to the tropi ...

''; the leaves of the tea plant; and kola nuts. Other sources include the leaves of yaupon holly, South American holly

yerba mate Yerba mate or yerba maté (), ''Ilex paraguariensis'', is a plant species of the holly genus native to South America. It was named by the French botanist Augustin Saint-Hilaire. The leaves of the plant can be steeped in hot water to make a bev ...

, and Amazonian holly guayusa; and seeds from Amazonian maple guarana berries. Temperate climates around the world have produced unrelated caffeine-containing plants. Caffeine in plants acts as a natural

pesticide Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for approximately 50% of all p ...

: 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

vacuole A vacuole () is a membrane-bound organelle which is present in Plant cell, plant and Fungus, fungal Cell (biology), cells and some protist, animal, and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water ...

s where it is complexed with

polyphenol Polyphenols () are a large family of naturally occurring phenols. They are abundant in plants and structurally diverse. Polyphenols include phenolic acids, flavonoids, tannic acid, and ellagitannin, some of which have been used historically as ...

s. 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

pollen Pollen is a powdery substance produced by most types of flowers of seed plants for the purpose of sexual reproduction. It consists of pollen grains (highly reduced Gametophyte#Heterospory, microgametophytes), which produce male gametes (sperm ...

producing plants by enhancing the reward memory of pollinators such as

honey bee A honey bee (also spelled honeybee) is a eusocial flying insect within the genus ''Apis'' of the bee clade, all native to mainland Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the ...

s. The differing perceptions in the effects of ingesting beverages made from various plants containing caffeine could be explained by the fact that these beverages also contain varying mixtures of other methylxanthine

s, including the cardiac stimulants theophylline and theobromine, and polyphenols that can form insoluble complexes with caffeine.

Products

Products containing caffeine include coffee, tea,

soft drink A soft drink (see #Terminology, § Terminology for other names) is a class of non-alcoholic drink, usually (but not necessarily) Carbonated water, carbonated, and typically including added Sweetness, sweetener. Flavors used to be Natural flav ...

s ("colas"), energy drinks, other beverages,

, caffeine tablets, other oral products, and inhalation products. According to a 2020 study in the United States, coffee is the major source of caffeine intake in middle-aged adults, while soft drinks and tea are the major sources in adolescents. Energy drinks are more commonly consumed as a source of caffeine in adolescents as compared to adults.

Beverages

Coffee

The world's primary source of caffeine is the coffee "bean" (the seed of the coffee plant), from which coffee is brewed. Caffeine content in coffee varies widely depending on the type of coffee bean and the method of preparation used; even beans within a given bush can show variations in concentration. In general, one serving of coffee ranges from 80 to 100 milligrams, for a single shot (30 milliliters) of arabica-variety

, to approximately 100–125 milligrams for a cup (120 milliliters) of drip coffee. '' Arabica'' coffee typically contains half the caffeine of the '' robusta'' variety. In general, dark-roast coffee has slightly less caffeine than lighter roasts because the roasting process reduces caffeine content of the bean by a small amount.

Tea

Tea contains more caffeine than coffee by dry weight. A typical serving, however, contains much less, since less of the product is used as compared to an equivalent serving of coffee. Also contributing to caffeine content are growing conditions, processing techniques, and other variables. Thus, teas contain varying amounts of caffeine. Tea contains small amounts of theobromine and slightly higher levels of theophylline than coffee. Preparation and many other factors have a significant impact on tea, and color is a poor indicator of caffeine content. Teas like the pale Japanese

green tea Green tea is a type of tea made from the leaves and buds of the '' Camellia sinensis'' that have not undergone the withering and oxidation process that creates oolong teas and black teas. Green tea originated in China in the late 1st millenn ...

, ''

gyokuro is a type of green tea from Japan. It differs from the standard ''sencha'' (a classic green tea grown in the sun) in being grown under the shade rather than the full sun. The name "gyokuro" translates as "jewel dew" (or "jade dew"). According to ...

'', for example, contain far more caffeine than much darker teas like '' lapsang souchong'', which has minimal caffeine content.

Soft drinks and energy drinks

Caffeine is also a common ingredient of

s, such as

, originally prepared from kola nuts. Soft drinks typically contain 0 to 55 milligrams of caffeine per 12 ounce () serving. By contrast, energy drinks, such as Red Bull, can start at 80 milligrams of caffeine per serving. The caffeine in these drinks either originates from the ingredients used or is an additive derived from the product of decaffeination or from chemical synthesis. Guarana, a primary ingredient of energy drinks, contains large amounts of caffeine with small amounts of theobromine and theophylline in a naturally occurring slow-release excipient.

Other beverages

* Maté is a drink popular in many parts of South America. Its preparation consists of filling a gourd with the leaves of the South American holly

, pouring hot but not boiling water over the leaves, and drinking with a straw, the bombilla, which acts as a filter so as to draw only the liquid and not the yerba leaves. * Guaraná is a soft drink originating in Brazil made from the seeds of the Guaraná fruit. * The leaves of '' Ilex guayusa'', the Ecuadorian holly tree, are placed in boiling water to make a guayusa tea. * The leaves of '' Ilex vomitoria'', the yaupon holly tree, are placed in boiling water to make a yaupon tea. * Commercially prepared coffee- flavoured milk beverages are popular in Australia. Examples include Oak's Ice Coffee and Farmers Union Iced Coffee. The amount of caffeine in these beverages can vary widely. Caffeine concentrations can differ significantly from the manufacturer's claims.

Cacao solids

Cocoa solids (derived from

) contain 230 mg caffeine per 100 g. The caffeine content varies between cocoa bean strains. Caffeine content mg/g (sorted by lowest caffeine content): * Forastero (defatted): 1.3 mg/g * Nacional (defatted): 2.4 mg/g * Trinitario (defatted): 6.3/g * Criollo (defatted): 11.3 mg/g

Chocolate

Caffeine per 100 g: * Dark chocolate, 70-85% cacao solids: 80 mg * Dark chocolate, 60-69% cacao solids: 86 mg * Dark chocolate, 45- 59% cacao solids: 43 mg *

Milk chocolate Milk chocolate is a form of solid chocolate containing Chocolate liquor, cocoa, sugar and milk. It is the most consumed types of chocolate, type of chocolate, and is used in a wide diversity of chocolate bar, bars, tablets and other confectione ...

: 20 mg The stimulant effect of chocolate may be due to a combination of theobromine and theophylline, as well as caffeine.

Tablets

Tablets offer several advantages over coffee, tea, and other caffeinated beverages, including convenience, known dosage, and avoidance of concomitant intake of sugar, acids, and fluids. The use of caffeine in this form is said to improve 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 SpazzStick, a caffeinated lip balm. 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. There is weak evidence that the use of caffeine mouth washes might help cognitive performance.

Inhalants

Similar to an e-cigarette, a caffeine inhaler may be used to deliver caffeine or a stimulant like guarana by vaping. In 2012, the FDA sent a warning letter to one of the companies marketing an inhaler, expressing concerns for the lack of safety information available about inhaled caffeine.

Combinations with other drugs

* Some beverages combine

with caffeine to create a caffeinated alcoholic drink. The stimulant effects of caffeine may mask the

effects of alcohol, potentially reducing the user's awareness of their level of intoxication. Such beverages have been the subject of bans due to safety concerns. In particular, the

United States Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

has classified caffeine added to malt liquor beverages as an "unsafe food additive". * Ya ba contains a combination of

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...

and caffeine. * Painkillers such as propyphenazone/paracetamol/caffeine combine caffeine with an

History

Discovery and spread of use

According to Chinese legend, the Chinese emperor Shennong, 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 '' Cha Jing'', 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

Sufi Sufism ( or ) is a mysticism, mystic body of religious practice found within Islam which is characterized by a focus on Islamic Tazkiyah, purification, spirituality, ritualism, and Asceticism#Islam, asceticism. Practitioners of Sufism are r ...

monasteries of the

Yemen Yemen, officially the Republic of Yemen, is a country in West Asia. Located in South Arabia, southern Arabia, it borders Saudi Arabia to Saudi Arabia–Yemen border, the north, Oman to Oman–Yemen border, the northeast, the south-eastern part ...

in southern Arabia. From Mokha, coffee spread to

Egypt Egypt ( , ), officially the Arab Republic of Egypt, is a country spanning the Northeast Africa, northeast corner of Africa and Western Asia, southwest corner of Asia via the Sinai Peninsula. It is bordered by the Mediterranean Sea to northe ...

and North Africa, and by the 16th century, it had reached the rest of the Middle East,

Persia Iran, officially the Islamic Republic of Iran (IRI) and also known as Persia, is a country in West Asia. It borders Iraq to the west, Turkey, Azerbaijan, and Armenia to the northwest, the Caspian Sea to the north, Turkmenistan to the nort ...

and

Turkey Turkey, officially the Republic of Türkiye, is a country mainly located in Anatolia in West Asia, with a relatively small part called East Thrace in Southeast Europe. It borders the Black Sea to the north; Georgia (country), Georgia, Armen ...

. From the Middle East, coffee drinking spread to Italy, then to the rest of Europe, and coffee plants were transported by the Dutch to the

East Indies The East Indies (or simply the Indies) is a term used in historical narratives of the Age of Discovery. The ''Indies'' broadly referred to various lands in Eastern world, the East or the Eastern Hemisphere, particularly the islands and mainl ...

and to the Americas. Kola nut use appears to have ancient origins. It is chewed in many

West Africa West Africa, also known as Western Africa, is the westernmost region of Africa. The United Nations geoscheme for Africa#Western Africa, United Nations defines Western Africa as the 16 countries of Benin, Burkina Faso, Cape Verde, The Gambia, Gha ...

n 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 ancient Mayan pot dated to 600 BCE. Also,

was consumed in a bitter and spicy drink called ''xocolatl'', often seasoned with

vanilla Vanilla is a spice derived from orchids of the genus ''Vanilla (genus), Vanilla'', primarily obtained from pods of the flat-leaved vanilla (''Vanilla planifolia, V. planifolia''). ''Vanilla'' is not Autogamy, autogamous, so pollination ...

, chile pepper, and achiote. ''Xocolatl'' was believed to fight fatigue, a belief probably attributable to the theobromine and caffeine content. Chocolate was an important luxury good throughout

pre-Columbian In the history of the Americas, the pre-Columbian era, also known as the pre-contact era, or as the pre-Cabraline era specifically in Brazil, spans from the initial peopling of the Americas in the Upper Paleolithic to the onset of European col ...

Mesoamerica Mesoamerica is a historical region and cultural area that begins in the southern part of North America and extends to the Pacific coast of Central America, thus comprising the lands of central and southern Mexico, all of Belize, Guatemala, El S ...

, and cocoa beans were often used as currency. ''Xocolatl'' was introduced to

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

by the

Spaniards Spaniards, or Spanish people, are a Romance-speaking ethnic group native to the Iberian Peninsula, primarily associated with the modern nation-state of Spain. Genetically and ethnolinguistically, Spaniards belong to the broader Southern a ...

, and became a popular beverage by 1700. The Spaniards also introduced the cacao tree into the

West Indies The West Indies is an island subregion of the Americas, surrounded by the Atlantic Ocean, North Atlantic Ocean and the Caribbean Sea, which comprises 13 independent island country, island countries and 19 dependent territory, dependencies in thr ...

and the

Philippines The Philippines, officially the Republic of the Philippines, is an Archipelagic state, archipelagic country in Southeast Asia. Located in the western Pacific Ocean, it consists of List of islands of the Philippines, 7,641 islands, with a tot ...

. The leaves and stems of the yaupon holly ('' Ilex vomitoria'') were used by Native Americans to brew a tea called ''asi'' or the " black drink". Archaeologists have found evidence of this use far into antiquity, possibly dating to Late Archaic times.

Chemical identification, isolation, and synthesis

In 1819, the German chemist Friedlieb Ferdinand Runge isolated caffeine for the first time; he called it ''"Kaffebase"'' (i.e., a base that exists in coffee). In 1821, caffeine was isolated both by the French chemist Pierre Jean Robiquet and by another pair of French chemists, Pierre-Joseph Pelletier and Joseph Bienaimé Caventou, according to Swedish chemist Jöns Jacob Berzelius in his yearly journal. Furthermore, Berzelius stated that the French chemists had made their discoveries independently of any knowledge of Runge's or each other's work. However, Berzelius later acknowledged Runge's priority in the extraction of caffeine, stating: "However, at this point, it should not remain unmentioned that Runge (in his ''Phytochemical Discoveries'', 1820, pages 146–147) specified the same method and described caffeine under the name ''Caffeebase'' a year earlier than Robiquet, to whom the discovery of this substance is usually attributed, having made the first oral announcement about it at a meeting of the Pharmacy Society in Paris." Pelletier's article on caffeine was the first to use the term in print (in the French form from the French word for coffee: '). It corroborates Berzelius's account: Robiquet was one of the first to isolate and describe the properties of pure caffeine, whereas Pelletier was the first to perform an elemental analysis. In 1827, M. Oudry isolated "théine" from tea, but in 1838 it was proved by Mulder and by Carl Jobst that theine was actually the same as caffeine. In 1895, German chemist

Hermann Emil Fischer Hermann Emil Louis Fischer (; 9 October 1852 – 15 July 1919) was a German chemist and List of Nobel laureates in Chemistry, 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He also developed the Fisch ...

(1852–1919) first synthesized caffeine from its chemical components (i.e. a "

total synthesis Total synthesis, a specialized area within organic chemistry, focuses on constructing complex organic compounds, especially those found in nature, using laboratory methods. It often involves synthesizing natural products from basic, commercially ...

"), and two years later, he also derived the structural formula of the compound. This was part of the work for which Fischer was awarded the

Nobel Prize The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...

in 1902.

Historic regulations

Because it was recognized that coffee contained some compound that acted as a stimulant, first coffee and later also caffeine has sometimes been subject to regulation. For example, in the 16th century Islamists in

Mecca Mecca, officially Makkah al-Mukarramah, is the capital of Mecca Province in the Hejaz region of western Saudi Arabia; it is the Holiest sites in Islam, holiest city in Islam. It is inland from Jeddah on the Red Sea, in a narrow valley above ...

and in the

Ottoman Empire The Ottoman Empire (), also called the Turkish Empire, was an empire, imperial realm that controlled much of Southeast Europe, West Asia, and North Africa from the 14th to early 20th centuries; it also controlled parts of southeastern Centr ...

made coffee illegal for some classes.

Charles II of England Charles II (29 May 1630 – 6 February 1685) was King of Scotland from 1649 until 1651 and King of England, Scotland, and King of Ireland, Ireland from the 1660 Restoration of the monarchy until his death in 1685. Charles II was the eldest su ...

tried to ban it in 1676, Frederick II of Prussia banned it in 1777, and coffee was banned in

Sweden Sweden, formally the Kingdom of Sweden, is a Nordic countries, Nordic country located on the Scandinavian Peninsula in Northern Europe. It borders Norway to the west and north, and Finland to the east. At , Sweden is the largest Nordic count ...

at various times between 1756 and 1823. In 1911, caffeine became the focus of one of the earliest documented health scares, when the US government seized 40 barrels and 20 kegs of

Coca-Cola Coca-Cola, or Coke, is a cola soft drink manufactured by the Coca-Cola Company. In 2013, Coke products were sold in over 200 countries and territories worldwide, with consumers drinking more than 1.8 billion company beverage servings ...

syrup in

Chattanooga, Tennessee Chattanooga ( ) is a city in Hamilton County, Tennessee, United States, and its county seat. It is located along the Tennessee River and borders Georgia (U.S. state), Georgia to the south. With a population of 181,099 in 2020, it is Tennessee ...

, alleging the caffeine in its drink was "injurious to health". Although the

Supreme Court In most legal jurisdictions, a supreme court, also known as a court of last resort, apex court, high (or final) court of appeal, and court of final appeal, is the highest court within the hierarchy of courts. Broadly speaking, the decisions of ...

later ruled in favor of Coca-Cola in '' United States v. Forty Barrels and Twenty Kegs of Coca-Cola'', two bills were introduced to the U.S. House of Representatives in 1912 to amend the

Pure Food and Drug Act The s:Pure Food and Drug Act of 1906, Pure Food and Drug Act of 1906, also known as the Wiley Act and Harvey Washington Wiley, Dr. Wiley's Law, was the first of a series of significant consumer protection laws enacted by the United States Con ...

, adding caffeine to the list of "habit-forming" and "deleterious" substances, which must be listed on a product's label.

Society and culture

Regulations

United States

The US Food and Drug Administration (FDA) considers safe beverages containing less than 0.02% caffeine; but caffeine powder, which is sold as a dietary supplement, is unregulated. It is a regulatory requirement that the label of most prepackaged foods must declare a list of ingredients, including food additives such as caffeine, in descending order of proportion. However, there is no regulatory provision for mandatory quantitative labeling of caffeine, (e.g., milligrams caffeine per stated serving size). There are a number of food ingredients that naturally contain caffeine. These ingredients must appear in food ingredient lists. However, as is the case for "food additive caffeine", there is no requirement to identify the quantitative amount of caffeine in composite foods containing ingredients that are natural sources of caffeine. While coffee or chocolate are broadly recognized as caffeine sources, some ingredients (e.g., guarana, yerba maté) are likely less recognized as caffeine sources. For these natural sources of caffeine, there is no regulatory provision requiring that a food label identify the presence of caffeine nor state the amount of caffeine present in the food. The FDA guidance was updated in 2018.

Consumption

Global consumption of caffeine has been estimated at 120,000 tonnes per year, making it the world's most popular psychoactive substance. The consumption of caffeine has remained stable between 1997 and 2015. Coffee, tea and soft drinks are the most common caffeine sources, with energy drinks contributing little to the total caffeine intake across all age groups.

Religions

The

Seventh-day Adventist Church The Seventh-day Adventist Church (SDA) is an Adventist Protestant Christian denomination which is distinguished by its observance of Saturday, the seventh day of the week in the Christian (Gregorian) and the Hebrew calendar, as the Sa ...

asked for its members to "abstain from caffeinated drinks", but has removed this from

baptismal vows Baptismal vows are the renunciations required of an adult candidate for baptism just before the sacrament is conferred. In the case of an infant baptism they are given by the godparents (sponsors) or parents themselves. In many Christian denomin ...

(while still recommending abstention as policy). Some from these religions believe that one is not supposed to consume a non-medical, psychoactive substance, or believe that one is not supposed to consume a substance that is addictive.

The Church of Jesus Christ of Latter-day Saints The Church of Jesus Christ of Latter-day Saints, informally known as the LDS Church or Mormon Church, is a Nontrinitarianism, nontrinitarian Restorationism, restorationist Christianity, Christian Christian denomination, denomination and the ...

has said the following with regard to caffeinated beverages: "... the Church revelation spelling out health practices (Doctrine and Covenants 89) does not mention the use of caffeine. The Church's health guidelines prohibit alcoholic drinks, smoking or chewing of tobacco, and 'hot drinks' – taught by Church leaders to refer specifically to tea and coffee." Gaudiya Vaishnavas generally also abstain from caffeine, because they believe it clouds the mind and overstimulates the senses. To be initiated under a guru, one must have had no caffeine, alcohol, nicotine or other drugs, for at least a year. Caffeinated beverages are widely consumed by

Muslims Muslims () are people who adhere to Islam, a Monotheism, monotheistic religion belonging to the Abrahamic religions, Abrahamic tradition. They consider the Quran, the foundational religious text of Islam, to be the verbatim word of the God ...

. In the 16th century, some Muslim authorities made unsuccessful attempts to ban them as forbidden "intoxicating beverages" under

Islamic dietary laws Islamic dietary laws are laws that Muslims follow in their diet. Islamic jurisprudence specifies which foods are halal () and which are haram (). The dietary laws are found in the Quran, the holy book of Islam, as well as in hadith, collections ...

Other organisms

The bacteria '' Pseudomonas putida'' CBB5 can live on pure caffeine and can cleave caffeine into carbon dioxide and ammonia. Caffeine is toxic to birds and to dogs and cats, and has a pronounced adverse effect on

mollusk Mollusca is a phylum of protostomic invertebrate animals, whose members are known as molluscs or mollusks (). Around 76,000 extant species of molluscs are recognized, making it the second-largest animal phylum after Arthropoda. The ...

s, various insects, and

spider Spiders (order (biology), order Araneae) are air-breathing arthropods that have eight limbs, chelicerae with fangs generally able to inject venom, and spinnerets that extrude spider silk, silk. They are the largest order of arachnids and ran ...

s. 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

haploid Ploidy () is the number of complete sets of chromosomes in a cell (biology), cell, and hence the number of possible alleles for Autosome, autosomal and Pseudoautosomal region, pseudoautosomal genes. Here ''sets of chromosomes'' refers to the num ...

wheat Wheat is a group of wild and crop domestication, domesticated Poaceae, grasses of the genus ''Triticum'' (). They are Agriculture, cultivated for their cereal grains, which are staple foods around the world. Well-known Taxonomy of wheat, whe ...

References

Bibliography

* * * *

External links

GMD MS Spectrum

at ''

The Periodic Table of Videos ''Periodic Videos'' (also known as ''The Periodic Table of Videos'') is a video project and YouTube channel on chemistry. It consists of a series of videos about chemical elements and the periodic table, with additional videos on other topics i ...

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