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Caffeine
1,3,7-Trimethylxanthine
Guaranine, Theine, Mateine, Methyltheobromine, Coffeine
Coffea arabica; Camellia sinensis
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-promotingcitation needed, cognitive-enhancing, and physical performance-boosting properties. While it has a generally favorable safety profile1, regular heavy use can produce physical dependencecitation needed. Pure powder forms carry a greater risk of accidental overdose2.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Threshold~10 mg
Light10-75 mg
Moderate75-250 mg
Strong250-400 mg
Heavy400+ mg
Bioavailability
99%3
The estimated lethal dose threshold is around 3,000 mg. For reference, a typical cup of coffee contains approximately 75-150 mg of caffeine.
Duration
Onset5-10 minutes
Peak1-3 hours
After Effects3-4 hours
Total3-5 hours
Half-life
~5 hours
Subjective Effects
Legacy content. A statistically backed ontology from Mindstate Design Labs is coming soon.
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.
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.
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.citation needed The wakefulness-promoting properties are specifically attributed to A2A receptor antagonism, which reduces inhibitory GABA neurotransmission to histaminergic arousal centers in the tuberomammillary nucleus. 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. 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.
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.citation needed 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%). 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. The elimination half-life is approximately 5 hours in healthy adults, though this varies considerably with smoking status, pregnancy, and age.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese 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.
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
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
LowCaffeine 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,citation needed and some users report difficulty reducing intake despite awareness of negative effects.
Physical
LowA mild form of physical dependence develops with regular daily use above 100 mg.citation needed Withdrawal symptoms include headache, fatigue, irritability, depressed mood, difficulty concentrating, and flu-like symptoms,4 typically beginning within 24 hours of cessation and generally resolving within one day.citation needed
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;citation needed 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.citation needed
Skeletal
In postmenopausal women, high caffeine consumption has been associated with accelerated bone loss.citation needed
Muscular
Rhabdomyolysis has been reported in cases of very high caffeine intake exceeding 5 grams, a dose approaching lethal levels.citation needed
Psychosis Risk
Psychotic symptoms including delusions, hallucinations, mania, disorientation, and disinhibition may occur only at very high doses exceeding 5 grams, approaching lethal levels.citation needed At typical consumption, caffeine may induce or worsen anxiety rather than psychosis; caffeine-induced anxiety disorder is recognized in the DSM-5.
Seizure Risk
Seizures may occur in cases of caffeine overdose due to central nervous system overstimulation.citation needed 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.citation needed…
Legality
By Country
Prescription1
ChinaPrescription onlyCaffeine 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.
Legal / decriminalized7
United StatesLegal (regulated)21 CFR § 182.1180 (Caffeine); Federal Food, Drug, and Cosmetic Act § 402(f)(1)(A), 21 U.S.C. § 342(f)(1)(A)363738394041424344
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.
IllinoisRestricted410 ILCS 647/15, 647/20, 647/2545
Illinois prohibits selling, offering for sale, giving away, or providing free samples of powdered pure caffeine to persons under 18 in the state, subject to a federal-approval exception. A violation is a Class A misdemeanor, and a second or subsequent violation is a Class 4 felony.
OhioRestrictedOhio Rev. Code § 2925.3446
Ohio prohibits knowingly selling or offering for sale a pure caffeine product, defined as a crystalline, liquid, or powdered product consisting solely or primarily of caffeine. FDA-compliant coffee, tea, soft drinks, energy drinks, other caffeine-containing beverages, and energy products are excluded. Unit-dose pills, tablets, and caplets containing no more than 250 milligrams of caffeine per unit remain permitted. A violation is a minor misdemeanor for a first offense and a third-degree misdemeanor for a subsequent offense.
ColombiaLegal (regulated)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.
IndonesiaLegal (regulated)Peraturan Badan Pengawas Obat dan Makanan Nomor 29 Tahun 2023 tentang Persyaratan Keamanan dan Mutu Obat Bahan Alam1718
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.
PolandLegal (regulated)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.
South AfricaLegal (regulated)Medicines and Related Substances Act schedules23
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)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. 25452829303132
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.
TurkeyLegal (regulated)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.
Not scheduled5
ChileNot scheduledDecreto Supremo No. 867/2007, regulations implementing Ley No. 20.0007
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.
DenmarkNot scheduledBekendtgørelse om euforiserende stoffer, Bilag 114
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.
FinlandNot scheduledGovernment Decree 543/2008 on substances, preparations and plants considered narcotics15
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.
GermanyNot scheduledBetäubungsmittelgesetz, Anlagen I–III16
Caffeine is not included in Germany's narcotics schedules under the Betäubungsmittelgesetz. It is therefore not a scheduled Betäubungsmittel.
SwedenNot scheduledCaffeine 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.
References
Source Pages
Citations
- Justin Evans, John R. Richards, & Amanda S. Battisti. (n.d.). Caffeine - StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK519490/12
- Pure and Highly Concentrated Caffeine. (n.d.). https://www.fda.gov/food/information-select-dietary-supplement-ingredients-and-other-substances/pure-and-highly-concentrated-caffeine1
- Ewa Poleszak, Aleksandra Szopa, Elżbieta Wyska, Wirginia Kukuła-Koch, Anna Serefko, Sylwia Wośko, Karolina Bogatko, Andrzej Wróbel, & Piotr Wlaź. (2016). Caffeine augments the antidepressant-like activity of mianserin and agomelatine in forced swim and tail suspension tests in mice. https://doi.org/10.1016/j.pharep.2015.06.1381
- Caffeine Withdrawal. StatPearls (2025-12-13). https://www.ncbi.nlm.nih.gov/books/NBK430790/1
- By the King. A PROCLAMATION FOR THE Suppression of Coffee-Houses. (n.d.). http://www.uni-giessen.de/gloning/tx/suppress.htm1
- Mormonism in the News: Getting It Right August 29. The Church of Jesus Christ of Latter-Day Saints (2012). https://newsroom.churchofjesuschrist.org/article/mormonism-news--getting-it-right-august-291
- Decreto Supremo No. 867/2007, regulations implementing Ley No. 20.000. ispch.cl (n.d.). https://www.ispch.cl/sites/default/files/5_agencia_reguladora/decreto_867_07.pdf1
- 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）》. nmpa.gov.cn (n.d.). https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20250728092519123.html1
- 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）》. xzfg.moj.gov.cn (n.d.). https://xzfg.moj.gov.cn/front/law/detail?LawID=17441
- 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）》. yjj.sh.gov.cn (n.d.). https://yjj.sh.gov.cn/qtgzwj/20250728/80ad6017cd9d41daa4181ddb4a044c9c.html1
Further Reading
Article Status
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Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
Josie Kins · Updated the article · also 1,4-Butanediol, 1B-LSD, 1cP-AL-LAD and 573 more
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