Caffeine

Caffeine

Clinical data
Pronunciation	/kæˈfiːn, ˈkæfiːn/
Other names	Guaranine Methyltheobromine 1,3,7-Trimethylxanthine 7-methyltheophylline[1] Theine
AHFS/Drugs.com	Monograph
License data	US DailyMed: Caffeine
Pregnancy category	AU: A
Dependence liability	Physical: Moderate 13% and variable low–high 10–73%[2] Psychological: Low–moderate[2]
Addiction liability	Relatively low: 9%[3] [failed verification]
Routes of administration	Common: By mouth Medical: Intravenous Uncommon: Insufflation, rectal, transdermal, topical
Drug class	Stimulant; Adenosinergic; Eugeroic; Nootropic; Anxiogenic; Analeptic; PDE inhibitor; Diuretic
ATC code	N06BC01 (WHO) D11AX26 (WHO), V04CG30 (WHO)
Legal status
Legal status	AU: Unscheduled BR: Unscheduled CA: Unscheduled DE: Unscheduled NZ: Unscheduled UK: General sales list (GSL, OTC) US: Unscheduled UN: Unscheduled CN: OTC In general Legal for all uses
Pharmacokinetic data
Bioavailability	99%[4]
Protein binding	10–36%[5]
Metabolism	Primary: CYP1A2[5] Minor: CYP2E1,[5] CYP3A4,[5] CYP2C8,[5] CYP2C9[5]
Metabolites	• Paraxanthine 84% • Theobromine 12% • Theophylline 4%
Onset of action	45 minutes–1 hour[4][6]
Elimination half-life	Adults: 3–7 hours[5] Infants (full term): 8 hours[5] Infants (premature): 100 hours[5]
Duration of action	3–4 hours[4]
Excretion	Urine (100%)
Identifiers
IUPAC name 1,3,7-Trimethyl-3,7-dihydro-1H-purine-2,6-dione
CAS Number	58-08-2
PubChem CID	2519
IUPHAR/BPS	407
DrugBank	DB00201
ChemSpider	2424
UNII	3G6A5W338E
KEGG	D00528
ChEBI	CHEBI:27732
ChEMBL	ChEMBL113
PDB ligand	CFF (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID0020232
ECHA InfoCard	100.000.329
Chemical and physical data
Formula	C8H10N4O2
Molar mass	194.194 g·mol−1
3D model (JSmol)	Interactive image
Density	1.23 g/cm3
Melting point	235 to 238 °C (455 to 460 °F) (anhydrous)[7][8]
SMILES CN1C=NC2=C1C(=O)N(C(=O)N2C)C
InChI InChI=1S/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3 Key:RYYVLZVUVIJVGH-UHFFFAOYSA-N
Data page
Caffeine (data page)

Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class and is the most commonly consumed psychoactive substance globally.^[9][10] It is mainly used for its eugeroic (wakefulness promoting), ergogenic (physical performance-enhancing), or nootropic (cognitive-enhancing) properties.^[11][12] Caffeine acts by blocking binding of adenosine at a number of adenosine receptor types, inhibiting the centrally depressant effects of adenosine and enhancing the release of acetylcholine.^[13] Caffeine has a three-dimensional structure similar to that of adenosine, which allows it to bind and block its receptors.^[14] 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.^[10][15]

Caffeine is a bitter, white crystalline purine, a methylxanthine alkaloid, and is chemically related to the adenine and guanine bases of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It is found in the seeds, fruits, nuts, or leaves of a number of plants native to Africa, East Asia and South America^[16] and helps to protect them against herbivores and from competition by preventing the germination of nearby seeds,^[17] as well as encouraging consumption by select animals such as honey bees.^[18] The best-known source of caffeine is the coffee bean, the seed of the Coffea plant. People may drink beverages containing caffeine to relieve or prevent drowsiness and to improve cognitive performance. To make these drinks, caffeine is extracted by steeping the plant product in water, a process called infusion. Caffeine-containing drinks, such as coffee, tea, and cola, are consumed globally in high volumes. In 2020, almost 10 million tonnes of coffee beans were consumed globally.^[19] Caffeine is the world's most widely consumed psychoactive drug.^[20][21] 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 with it even being encouraged.

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.^[22] It may confer a modest protective effect against some diseases,^[23] including Parkinson's disease.^[24] Some people experience sleep disruption or anxiety if they consume caffeine,^[25] 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.^[26][27] 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.^[28][29][2] Tolerance 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).^[30]

Caffeine is classified by the U.S. Food and Drug Administration (FDA) as generally recognized as safe. Toxic doses, over 10 grams per day for an adult, are much higher than the typical dose of under 500 milligrams per day.^[31] 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.^[32] 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, or espresso).^[33] Thus it requires roughly 50–100 ordinary cups of coffee to reach the toxic dose. However, pure powdered caffeine, which is available as a dietary supplement, can be lethal in tablespoon-sized amounts.