Caffeine

Caffeine
The skeletal formula of Caffeine.
Chemical Nomenclature
Common names	Caffeine
Substitutive name	3,7-dihydro-1,3,7-trimethyl-1h-purine-2,6-dione
Systematic name	1,3,7-Trimethylpurine-2,6-dione
Class Membership
Psychoactive class	Stimulant
Chemical class	Xanthine
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. DISCLAIMER: PW's dosage information is a summary of data gathered from users and resources. It is NOT a recommendation and should be verified with other sources for accuracy. Threshold 10 - 20 mg Light 20 - 50 mg Common 50 - 150 mg Strong 150 - 400 mg Heavy 400 mg + Duration Total 1.5 - 5 hours Onset 5 - 10 minutes Afterglow up to 24 hours

Summary sheet: Caffeine

Caffeine (3,7-dihydro-1,3,7-trimethyl-1h-purine-2,6-dione) is a bitter, white crystalline xanthine alkaloid and a stimulant drug that increases activity in the brain and induces temporary improvements including enhanced alertness, wakefulness, and locomotion.

Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants, as well as enhancing the reward memory of pollinators. 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.

Unlike many other psychoactive drugs, this substance 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. Caffiene 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.

Chemistry

Caffeine, or (1,3,7-Trimethylpurine-2,6-dione) is an synthetic alkaloid with a substituted xanthine core. Xanthine is a substituted purine, which contains two fused rings, a pyrimidine and imidazole. Pryimidine is a 6 membered ring with nitrogen constituents at R₁ and R₃; diazole is a 5 membered ring with nitrogen substituents at R₁ and R₂ . Xanthine contains oxygen groups double-bonded to R₂ and R₆. Caffeine contains additional methyl substitutions at R₁, R₃, and R₇ of its structure, bound to the open nitrogen groups of the xanthine skeleton. It is an achiral aromatic compound.

Pharmacology

Caffeine acts through several mechanisms, but its most important effect is to counteract a substance called adenosine that naturally circulates at high levels throughout the body, and especially in the nervous system. In the brain, adenosine plays a generally protective role, part of which is to reduce neural activity levels. The principal mode of action behind caffeine is as a nonselective antagonist of adenosine receptors. The caffeine molecule is structurally similar to adenosine, and is thus capable of binding to adenosine receptors on the surface of cells without activating them, thereby acting as a competitive inhibitor.

Along side of this, caffeine also has profound effects on most of the other major neurotransmitters, including dopamine, acetylcholine, serotonin, and, in high doses, on norepinephrine, 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, 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

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

The physical effects of caffeine can be broken down into several components which progressively intensify proportional to dosage. These are described below and generally include:

• Stimulation - In terms of its effects on the physical energy levels of the user, caffeine is usually considered to be mildly to moderately energetic and stimulating in a fashion that is considerably weaker in comparison to that of traditional recreational stimulants such as amphetamine, MDMA or cocaine. This encourages physical activities such as performing chores and repetitive tasks which would otherwise be boring and strenuous physical activities. The particular style of stimulation which caffeine presents can be described as forced. This means that at higher dosages, it becomes difficult or impossible to keep still as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in extreme shaking of the entire body, unsteadiness of the hands, and a general lack of motor control.
• Frequent urination - When doses of caffeine equivalent to 2–3 cups of coffee are administered to people who have not consumed caffeine during prior days, they produce a mild increase in urinary output. Most people who consume caffeine, however, ingest it daily. Regular users of caffeine have been shown to develop a strong tolerance to the diuretic effect.
• Vasoconstriction and Vasodilation - Whilst caffeine acts as a mild vasoconstrictor, it's metabolite theombrine is a vasodilator and these effects are thought to cancel each other out.
• Bronchodilation - Caffeine is an effective bronchodilator. In clinical tests on adults with athsma, at fairly low doses (5mg/kg of body weight), caffeine has been shown to provide a small improvement in lung function, such that it needs to be controlled for in diagnostic tests.
• Appetite suppression
• Tactile enhancement
• Increased heart rate
• Increased blood pressure

Cognitive effects

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.

The most prominent of these cognitive effects generally include:

• Wakefulness
• Thought acceleration
• Analysis enhancement
• Focus enhancement - This component is most effective at low to moderate dosages as anything higher will usually impair concentration.
• Memory enhancement
• Motivation enhancement
• Euphoria
• Anxiety
• Cognitive fatigue - This component can occur during the offset of this compound as a rebound effect which is usually equal in its intensity to the enhancements which occurred before it.

Toxicity and harm potential

Lethal dosage

Extreme overdose can result in death. 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. 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.

Tolerance and addiction potential

With repetitive use, physical dependence or addiction may occur. Also, some effects of caffeine, particularly the autonomic effects, decrease over time, a phenomenon known as a tolerance. Tolerance develops quickly to some (but not all) effects of caffeine, especially among heavy coffee and energy drink consumers. Some coffee drinkers develop tolerance to its sleep-disrupting effects, but others apparently do not.

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.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. 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

Main article: Stimulant 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.

Legal issues

Caffeine is legal in nearly all parts of the world. Because caffeine is a psychoactive drug however, it is often regulated. For example, in the United States the Food and Drug Administration (FDA) restricts beverages to containing less than 0.02% caffeine.

See also

• Responsible use
• Stimulants
• Nootropics
• Caffeine (Wikipedia)
• Caffeine (Erowid)