Caffeine is the most widely used psychoactive substance. Besides its well-known presence in coffee, tea, colas, and chocolate, it is available in many over-the-counter and prescription oral medications and as injectable caffeine sodium benzoate (occasionally used for neonatal apnea). Caffeine is widely used as an anorectant, a co-analgesic, a diuretic, and a sleep suppressant. Botanical forms of caffeine, including yerba mate, guarana (Paullinia cupana), kola nut (Cola nitida), and green tea extract, are common constituents of "thermogenic" dietary supplements that are widely touted for weight loss and athletic enhancement (see also Herbal and Alternative Products). Caffeine is occasionally combined in tablets with other stimulants, such as MDMA (methylenedioxymethamphetamine). Although caffeine has a wide therapeutic index and rarely causes serious toxicity, there are many documented cases of accidental, suicidal, and iatrogenic intoxication, some resulting in death.
In November of 2010, the FDA issued warnings to manufacturers of caffeinated alcoholic beverages to stop production due to public health safety concerns, and these have since been removed from sale in the United States.
Caffeine is a trimethylxanthine that is closely related to theophylline. It acts primarily through nonselective inhibition of adenosine receptors. In addition, with overdose there is considerable beta1- and beta2-adrenergic stimulation secondary to release of endogenous catecholamines.
Addition of caffeine to alcoholic beverages can decrease subjective perception of alcohol intoxication without affecting objective markers of intoxication such as motor control, and may increase risky sexual behavior and injury.
Pharmacokinetics. Caffeine is rapidly and completely absorbed orally, with a volume of distribution of 0.7–0.8 L/kg. Its elimination half-life is approximately 4–6 hours but can range from 3 hours in healthy smokers to 10 hours in nonsmokers; after overdose, the half-life may be as long as 15 hours. In infants younger than 2–3 months old, metabolism is extremely slow, and the half-life may exceed 24 hours (see also Table II–66). Caffeine is metabolized in the liver by cytochrome P450 (CYP), primarily the CYP1A2 isoenzyme, and is subject to several potential drug interactions, including inhibition by oral contraceptives, cimetidine, norfloxacin, and alcohol. Tobacco (and marijuana) smoking accelerates caffeine metabolism.
The reported lethal oral dose is 10 g (150–200 mg/kg), although one case report documents survival after a 24-g ingestion. In children, ingestion of 35 mg/kg may lead to moderate toxicity. Coffee contains 50–200 mg (tea, 40–100 mg) of caffeine per cup depending on how it is brewed. No-Doz and other sleep suppressants usually contain about 200 mg per tablet. "Thermogenic" dietary supplements, which are sold as energy beverages (eg, Red Bull), bars, capsules, tablets, or liquid drops, contain the equivalent of 40–200 mg of caffeine per serving as either concentrated plant extracts or synthetic caffeine (see Table II–17).