Caffeine

Summary sheet: Caffeine

For the coffee plant, see Coffea (botany).

Caffeine
Chemical Nomenclature
Common names	Caffeine
Substitutive name	1,3,7-Trimethylxanthine[1]
Systematic name	1,3,7-Trimethylpurine-2,6-dione[2]
Class Membership
Psychoactive class	Stimulant
Chemical class	Xanthine
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Threshold 10 mg Light 20 - 50 mg Common 50 - 150 mg Strong 150 - 500 mg Heavy 500 mg + Duration Total 2 - 5 hours Onset 5 - 10 minutes Peak 1 - 2 hours After effects 2 - 4 hours ⇣ Insufflated Dosage Threshold 2.5 mg Light 10 - 25 mg Common 25 - 40 mg Strong 40 - 80 mg Heavy 80 mg + Duration Total 1 - 2.5 hours Onset 0.5 - 2 minutes Peak 0.5 - 1 hours After effects 6 - 24 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions
DOx
25x-NBOMe
ΑMT
PCP
Amphetamines
MDMA
Cocaine

1,3,7-Trimethylxanthine (also known as caffeine) is a naturally-occurring stimulant substance of the xanthine class. Notable effects include stimulation, wakefulness, enhanced focus and motivation. It is the most widely consumed psychoactive substance in the world.

Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants where it acts as a natural pesticide, as well as enhancing the reward memory of pollinators.^[3][4][5] It is most commonly consumed by humans in infusions extracted from the seed of the coffee plant and the leaves of the tea bush, as well as from various foods and drinks containing products derived from the kola nut.^{[citation needed]}

Unlike many other psychoactive drugs, caffeine is legal and unregulated in nearly all parts of the world. Beverages containing caffeine, such as coffee, tea, soft drinks, and energy drinks, enjoy great popularity. Caffeine is the most commonly used drug in the world, with 90% of adults in North America consuming it on a daily basis. Global consumption of caffeine has been estimated at 120,000 tonnes per year, making it the world's most popular psychoactive substance. This amounts to one serving of a caffeinated beverage for every person every day.^[6]

Chemistry

Caffeine, or 1,3,7-trimethylpurine-2,6-dione, is an alkaloid with a substituted xanthine core. Xanthine is a substituted purine comprised of two fused rings: a pyrimidine and an imidazole. Pryimidine is a six-membered ring with nitrogen constituents at R₁ and R₃; imidazole is a 5 membered ring with nitrogen substituents at R₁ and R₃. Xanthine contains oxygen groups double-bonded to R₂ and R₆.

Caffeine contains additional methyl substitutions at R₁, R₃ and R₇ of its structure. These are bound to the open nitrogen groups of the xanthine skeleton. It is an achiral aromatic compound.

Pharmacology

The principal mechanism of action of caffeine is as a nonselective antagonist at the adenosine A₁ and A_2A receptors. During waking periods, the brain levels of the neurotransmitter adenosine steadily increase and trigger fatigue and sleepiness. The caffeine molecule is structurally similar to adenosine, which enables it to bind to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive inhibitor.^[7]

Alongside this, caffeine also has effects on most of the other major neurotransmitters, including dopamine, acetylcholine, serotonin, and, in high doses, on norepinephrine,^[8] and to a small extent epinephrine, glutamate, and cortisol. At high doses, exceeding 500 milligrams, caffeine inhibits GABA neurotransmission. GABA reduction explains why caffeine increases anxiety, insomnia, rapid heart and respiration rate at high dosages.

Metabolites

Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system, in particular, by the CYP1A2 isozyme, into three dimethylxanthines,^[9] each of which has its own effects on the body:

• Paraxanthine (84%): Increases lipolysis, leading to elevated glycerol and free fatty acid levels in the blood plasma.
• Theobromine (12%): Dilates blood vessels and increases urine volume. Theobromine is also the principal alkaloid in the cocoa bean, and therefore chocolate.
• Theophylline (4%): Relaxes smooth muscles of the bronchi, and is used to treat asthma. The therapeutic dose of theophylline, however, is many times greater than the levels attained from caffeine metabolism.

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), a research literature based on anecdotal reports and the personal experiences of PsychonautWiki contributors. As a result, they should be regarded with a healthy degree of skepticism. It is worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become much more likely with higher doses and may include addiction, serious injury, or death.

Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

• Erowid Experience Vaults: Caffeine

Toxicity and harm potential

Caffeine is not known to cause brain damage, and has an extremely low toxicity relative to dose. There are relatively few physical side effects associated with caffeine exposure. Various studies have shown that in reasonable doses in a careful context, it presents no negative cognitive, psychiatric or toxic physical consequences of any sort.

Lethal dosage

Extreme overdose can result in death.^[13][14] The median lethal dose (LD₅₀) given orally is 192 milligrams per kilogram in rats. The LD50 of caffeine in humans is dependent on individual sensitivity, but is estimated to be about 150 to 200 milligrams per kilogram of body mass or roughly 80 to 100 cups of coffee for an average adult.^[15] Though achieving lethal dose of caffeine would be difficult with regular coffee, it is easier to reach high doses with caffeine pills, and the lethal dose can be lower in individuals whose ability to metabolize caffeine is impaired.

It is strongly recommended that one use harm reduction practices when using this substance.

Dependence and abuse potential

Caffeine produces dependence with chronic use and has a low abuse potential. When dependence has developed, cravings and withdrawal effects will occur if one suddenly stops their use.

Tolerance to many of the effects of caffeine develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After tolerance has developed, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to return to baseline in the absence of further consumption. Caffeine presents cross-tolerance with antagonists adenosine receptors, meaning that after the consumption of caffeine certain stimulants such as theacrine and theobromine will have a reduced effect.

Withdrawal symptoms

Withdrawal symptoms – including headaches, irritability, inability to concentrate, drowsiness, insomnia, and pain in the stomach, upper body, and joints –- may appear within 12 to 24 hours after discontinuation of caffeine intake, peak at roughly 48 hours, and usually last from 2 to 9 days.^[16] Withdrawal headaches are experienced by 52% of people who stopped consuming caffeine for two days after an average of 235 mg caffeine per day prior to that.^[17] In prolonged caffeine drinkers, symptoms such as increased depression and anxiety, nausea, vomiting, physical pains and intense desire for caffeine containing beverages are also reported. Peer knowledge, support and interaction may aid withdrawal.

Psychosis

There is limited evidence that caffeine, in high doses or when chronically abused, may induce psychosis in normal individuals and worsen pre-existing psychosis in those diagnosed with schizophrenia.^[18][19] Caffeine has been shown to potentiate the effects of methamphetamine, which can also induce psychosis.^[20][21]

Dangerous interactions

Although many psychoactive substances are reasonably safe to use on their own, they can suddenly become dangerous or even life-threatening when combined with other substances. The following list includes some known dangerous combinations (although it is not guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

• DOx - High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating it may cause some physical discomfort.
• 25x-NBOMe - Caffeine can bring out the natural stimulation from psychedelic drugs to make it uncomfortable. High doses can cause anxiety which is hard to handle while tripping.
• ΑMT - High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.
• PCP - Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.
• Amphetamines - This combination of stimulants is not generally necessary and may increase strain on the heart, as well as potentially causing anxiety and greater physical discomfort.
• MDMA - Caffeine is not really necessary with MDMA and increases any neurotoxic effects from MDMA.
• Cocaine - Both stimulants, risk of tachycardia, hypertension, and in extreme cases heart failure.

Legal status

Caffeine is legal in nearly all parts of the world. However, it is often regulated because it is a psychoactive substance. For example, in the United States, the Food and Drug Administration (FDA) restricts beverages to contain less than 0.02% caffeine.^[22] unless they are listed as a dietary supplement.^[23]

See also

• Responsible use
• Stimulants
• Nootropics
• Xanthines
• Theobromine
• 8-chlorotheophylline

External links

• Caffeine (Wikipedia)
• Caffeine (Erowid Vault)
• Caffeine (Isomer Design)

Literature

• Nehlig, A., Daval, J. L., & Debry, G. (1992). Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Research Reviews, 17(2), 139-170. PMID: 1356551

References