Caffeine

1,3,7-Trimethylxanthine

Guaranine, Theine, Mateine, Methyltheobromine, Coffeine

Coffea arabica; Camellia sinensis

Psychoactive Class

Stimulant

Chemical Class

Xanthine

Caffeine is a naturally occurring stimulant of the methylxanthine class and the most widely consumed psychoactive substance in the world.¹ Found in coffee beans, tea leaves, cacao, and numerous other plants, it is primarily used for its wakefulness-promoting¹, cognitive-enhancing, and physical performance-boosting properties. While it has a generally favorable safety profile¹, regular heavy use can produce physical dependence². Pure powder forms carry a greater risk of accidental overdose³.

Dosage & Duration

Dosage

Threshold~10 mg

Light10-75 mg

Moderate75-250 mg

Strong250-400 mg

Heavy400+ mg

Bioavailability

~100%

Lethal dose begins at approximately 3,000 mg. Average coffee contains 75–150 mg caffeine.

Duration

Onset5-10 minutes

Peak1-3 hours

After Effects3-4 hours

Total3-5 hours

Half-life

~5 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

The physical effects of caffeine can be broken down into several components which progressively intensify proportional to dosage.

Appetite suppression Tactile enhancement Increased heart rate Increased blood pressure

Cognitive

The cognitive effects of caffeine can be broken down into several components which progressively intensify proportional to dosage. It contains a large number of typical stimulant cognitive effects. Although negative side effects are usually mild at low to moderate dosages, they become increasingly likely to manifest themselves with higher amounts or extended usage. This particularly holds true during the offset of the experience.

Wakefulness Thought acceleration Analysis enhancementMemory enhancement Motivation enhancement Euphoria Anxiety

Forked from Subjective Effect Documentation

by Josie KinsSeptember 2015.

Reagent Testing

Loading reagent data

Expected colorimetric results are being prepared.

Pharmacology

Pharmacodynamics

Caffeine primarily acts as an antagonist at all four adenosine receptor subtypes (A1, A2A, A2B, and A3) in the central nervous system, blocking adenosine binding and inhibiting its depressant effects.⁴ The wakefulness-promoting properties are specifically attributed to A2A receptor antagonism, which reduces inhibitory GABA neurotransmission to histaminergic arousal centers in the tuberomammillary nucleus.⁵ Caffeine also indirectly modulates dopamine signaling through adenosine-dopamine receptor heteromers in the striatum (A1-D1 and A2A-D2) and promotes neurotransmitter release including monoamines and acetylcholine.⁶ At higher concentrations, caffeine nonselectively inhibits phosphodiesterase enzymes, enhances intracellular calcium release via ryanodine receptor activation, and antagonizes GABA receptors, though these secondary mechanisms typically engage at concentrations beyond those achieved through normal consumption.⁴

Pharmacokinetics

Caffeine is rapidly and nearly completely absorbed after oral administration, with bioavailability approaching 100% in adults and peak plasma concentrations reached within 30 minutes to 2 hours.⁷⁸ Metabolism occurs predominantly in the liver via the CYP1A2 enzyme through sequential demethylation, producing paraxanthine as the major metabolite (84%) along with theobromine (12%) and theophylline (4%).⁸⁹ Xanthine oxidase and N-acetyltransferase 2 (NAT2) also contribute to its metabolism, and the resulting products are further processed and excreted in urine as urates.⁹ The elimination half-life is approximately 5 hours in healthy adults, though this varies considerably with smoking status, pregnancy, and age.⁸

Interactions

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

Pregabalin

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

AmphetaminesAMTCocaineDiphenhydramineDOx compoundsDXMMDMAMephedroneNBOMe compoundsPCP

TripSit

Tolerance

Full Tolerance

Tolerance to certain effects, particularly cardiovascular responses such as elevated blood pressure, develops with regular daily consumption. Habitual users demonstrate significantly reduced blood pressure elevation compared to non-regular consumers.

Cross Tolerance

Other methylxanthines (theophylline, theobromine)

Harm Potential

Addiction & Dependence

Psychological

Low

Caffeine is habit-forming and commonly used daily by millions, though compulsive consumption under any circumstances has not been scientifically observed. Some diagnostic manuals classify caffeine addiction,¹⁰ and some users report difficulty reducing intake despite awareness of negative effects.

Physical

Low

A mild form of physical dependence develops with regular daily use above 100 mg.¹¹ Withdrawal symptoms include headache, fatigue, irritability, depressed mood, difficulty concentrating, and flu-like symptoms,¹² typically beginning within 24 hours of cessation and generally resolving within one day.¹²

Toxicity

Cardiovascular

High caffeine intake, particularly from energy drinks exceeding 320 mg, is associated with short-term cardiovascular effects including elevated blood pressure, prolonged QT interval, tachycardia, and heart palpitations;¹³ these effects are typically acute and dose-dependent, with tolerance developing to autonomic cardiovascular effects with chronic use.

Gastrointestinal

Caffeine stimulates gastric acid secretion and increases gastrointestinal motility; long-term high-dose consumption of coffee may contribute to stomach ulcer formation.¹⁵

Skeletal

In postmenopausal women, high caffeine consumption has been associated with accelerated bone loss.¹⁶

Muscular

Rhabdomyolysis has been reported in cases of very high caffeine intake exceeding 5 grams, a dose approaching lethal levels.¹⁷

Psychosis Risk

Psychotic symptoms including delusions, hallucinations, mania, disorientation, and disinhibition may occur only at very high doses exceeding 5 grams, approaching lethal levels.¹⁷ At typical consumption, caffeine may induce or worsen anxiety rather than psychosis; caffeine-induced anxiety disorder is recognized in the DSM-5.¹⁸

Seizure Risk

Seizures may occur in cases of caffeine overdose due to central nervous system overstimulation.¹⁷ Individuals with epilepsy or other seizure disorders should use caffeine with extreme caution.

History & Culture

Ancient Origins and Traditional Use

Caffeine-containing plants have been utilized by human cultures across multiple continents for millennia, with various civilizations independently discovering the stimulating properties of different botanical sources.¹⁹…

Legality

By Country

United StatesLegal (regulated)GRAS

21 CFR § 182.1180 (Caffeine); Federal Food, Drug, and Cosmetic Act § 402(f)(1)(A), 21 U.S.C. § 342(f)(1)(A)^{535455565758596061}

Caffeine has been listed since 1977 as generally recognized as safe when used in cola-type beverages in accordance with good manufacturing practice, subject to a 0.02 percent tolerance. A dietary supplement containing caffeine is adulterated when it presents a significant or unreasonable risk of illness or injury under its labeled or ordinary conditions of use; FDA identifies some products containing only pure or highly concentrated caffeine as adulterated on that basis. Interstate introduction or delivery of adulterated food is prohibited.

By state

Across the 50 states, D.C., and the permanent territories, most jurisdictions treat caffeine consistently with federal law, though a number of states impose their own controls or classifications that diverge from the federal position.

Illinois

RestrictedRetail sale ban

Ohio

RestrictedPure caffeine product

ChinaPrescription only第二类

国家药监局、公安部、国家卫生健康委公告2025年第55号《药用类精神药品目录（2025年版）》²⁵²⁶²⁷

Caffeine is listed as a Category II psychotropic substance in China’s 2025 medicinal psychotropic-substances catalogue. Retail sale of Category II psychotropics requires a licensed physician’s prescription and the stipulated dose; sale without a prescription, above the stipulated dose, or to minors is prohibited. Non-drug manufacturers using caffeine as a raw material for food, food additives, cosmetics, or paint must obtain provincial drug-regulator approval and purchase it from a designated producer or wholesaler.

DenmarkNot scheduled

Bekendtgørelse om euforiserende stoffer, Bilag 1³¹

Caffeine is not listed in the Danish lists of euphoriant substances. It is therefore outside the controls imposed by the executive order on euphoriant substances.

GermanyNot scheduled

Betäubungsmittelgesetz, Anlagen I–III³³

Caffeine is not included in Germany's narcotics schedules under the Betäubungsmittelgesetz. It is therefore not a scheduled Betäubungsmittel.

PolandLegal (regulated)Rozdział 3c

Ustawa z dnia 11 września 2015 r. o zdrowiu publicznym (t.j. Dz.U. 2026 poz. 149)^36373839

Caffeine (1,3,7-trimethylxanthine) is not listed as a psychotropic substance, narcotic drug, or new psychoactive substance in Poland’s current controlled-substance regulation, including its 2025 amendment, and is not captured by the defined NPS classes. It is nevertheless legally regulated in beverages: drinks with added caffeine exceeding 150 mg/l, excluding naturally occurring caffeine, may not be sold to persons under 18, on educational premises, or through vending machines. Producers and importers must label such products as an energy drink, and the Act also imposes a levy on drinks containing added caffeine.

SwedenNot scheduledBilaga 1

Förordning (1992:1554) om kontroll av narkotika^41424344

Caffeine is not scheduled as a narcotic or as a hälsofarlig vara in Sweden; Swedish narcotic and harmful-product controls apply to substances individually listed in their respective annexes, which do not include koffein or 1,3,7-trimetylxantin. The Swedish Medical Products Agency classifies caffeine as not narcotic. Caffeine is nevertheless prohibited as an ingredient in tobacco-free nicotine products from 1 January 2023.

TurkeyLegal (regulated)Enerji içeceği

Türk Gıda Kodeksi Enerji İçecekleri Tebliği (Tebliğ No: 2017/4)⁵⁰⁵¹⁵²

Turkey regulates caffeine in energy drinks under the Turkish Food Codex Energy Drinks Communiqué (Communiqué No. 2017/4), which entered into force on 30 June 2017. The Communiqué limits total caffeine in energy drinks to 150 mg/L and requires the caffeine amount to be shown on the label. Energy drinks may not be sold to persons under 18 or supplied or advertised in sports facilities, school canteens, or hospitals; violations are subject to sanctions under Law No. 5996.

ChileNot scheduled

Decreto Supremo No. 867/2007, regulations implementing Ley No. 20.000²⁴

Caffeine is not included in Chile's listed narcotic and psychotropic substances under Decreto Supremo No. 867/2007. It is therefore outside the controlled-substance schedules implementing Ley No. 20.000.

ColombiaLegal (regulated)Sustancias químicas autorizadas

Resolución 4150 de 2009²⁸²⁹³⁰

Colombia treats caffeine as a lawful regulated substance rather than a controlled drug; Constitutional Court judgment C-253/2019 identifies caffeine among the country's lawful drugs. Resolución 4150 de 2009 authorizes caffeine in energy drinks up to 32 mg per 100 mL and requires sanitary registration, caffeine-content labelling, and prior authorization of advertising. Those product rules have applied since May 2010, six months after publication in Diario Oficial No. 47.522 on 3 November 2009. Caffeine is absent from the current controlled-substances and special-control-medicines annexes, whose variation rules apply only to substances already listed; they do not prohibit caffeine possession, production, or sale as such.

FinlandNot scheduled

Government Decree 543/2008 on substances, preparations and plants considered narcotics³²

Caffeine is not included in Finland's annexes of substances, preparations and plants considered narcotics. It is therefore not a narcotic under Government Decree 543/2008.

IndonesiaLegal (regulated)Lampiran V

Peraturan Badan Pengawas Obat dan Makanan Nomor 29 Tahun 2023 tentang Persyaratan Keamanan dan Mutu Obat Bahan Alam³⁴³⁵

Caffeine (1,3,7-trimethylxanthine) is regulated in Indonesian natural-medicine products under BPOM Regulation No. 29 of 2023. Since 9 November 2023, products containing caffeine or caffeine-bearing herbs must limit natural caffeine to 50 mg per serving and 150 mg per day; coffee used as a flavouring is limited to 10 mg caffeine per serving. These safety and quality requirements are criteria for product marketing authorization.

South AfricaLegal (regulated)Injection only

Medicines and Related Substances Act schedules⁴⁰

Caffeine intended for injection is listed in South Africa's medicine schedules. Caffeine's legal status is therefore regulated by presentation rather than treated as a generally prohibited drug.

ThailandLegal (regulated)ยาอันตราย

Ministry of Public Health Notification Re: Dangerous Drugs (consolidated), issued under the Drug Act B.E. 2510; Ministerial Regulation on Designating Caffeine as a Controlled Commodity and Appointing Commodity Control Officers B.E. 2545^4546474849

Caffeine in a drug preparation exceeding 100 mg per single oral dose is a dangerous drug under the Ministry of Public Health Notification Re: Dangerous Drugs; the exception at or below that dose has applied since 8 August 1987. Dangerous drugs may be sold only by a licensed modern-drug seller while a pharmacist or veterinary practitioner is on duty. Raw caffeine and its salts are separately controlled commodities nationwide under the 2002 commodity-control measures, requiring written authorization for import or transport, sale, possession, use, or alteration, subject to stated exemptions for caffeine derivatives and registered finished medicines.

References

Source Pages

Citations

Suggest an edit

Spotted a mistake, an outdated claim, or something missing from the Caffeine article? Send the editors a private note. Feedback lands in a moderation queue and is never shown on the site.