Trimethylxanthine, or caffeine, is a feebly basic alkaloidal body usually prepared from damaged tea-leaves. It is found in plants growing in different parts of the world, and of no close botanic relationship; and the finding out, by the inhabitants of these different countries, of the value of their particular plant in making a stimulating beverage, and of the best way of preparing the part of the plant used, makes an interesting story.

In Arabia and Egypt the beverage was made from coffee, the roasted seeds; in western Africa, from kola, the dried seeds; in the Amazon region of South America, from guarana, a brittle mass made by pounding up the seeds to a paste and drying by heat; in China and Japan, from tea, the fermented leaves; in Paraguay and Uruguay, from mate or Paraguay tea, the dried leaves and shoots of a species of Ilex or holly. The Appalache tea (Ilex cassine), which grows from Virginia to the Gulf of Mexico, contains 0.12 per cent. of caffeine and 2.4 per cent. of tannin (Blyth, 1909). Having no caffeine plants, the inhabitants of Mexico and the West Indies made their stimulating beverage of the fermented seeds of the chocolate plant, which contain the close relative, theobromine. Mate contains about 1.3 per cent. of the alkaloid; tea, 1 to 4 per cent.; coffee, 0.6 to 2 per cent.; kola, 1 to 2 per cent.; and guarana, 3 to 6 per cent.

Preparations And Doses

Caffeine (caffeina) is soluble in 46 parts of water and 54 of alcohol. Dose, 1 grain (0.06 gm.).

Citrated caffeine (caffeina citrata) is a mixture of equal parts of caffeine and citric acid. On account of the feebly alkaloidal nature of caffeine, the citric acid is added in excess. It is soluble in 25 parts of water. Dose, 2 grains (0. 13 gm.). This is the favorite preparation.

Effervescent citrated caffeine (caffeina citrata effervescens) is a granular salt which contains 4 per cent. of citrated caffeine, i. e., 2 per cent. of caffeine, with citric and tartaric acids and sodium bicarbonate to make it effervesce when added to water. Dose, 50 grains (about two teaspoonfuls).

Guarana is assayed to contain not less than 4 per cent. of alkaloid. It contains much tannic acid. It has one official preparation, the fluidextract, dose, 30 minims (2 c.c).

Caffeine sodio-benzoate and caffeine sodio-salicylate are double salts which are soluble in twice their weight of water, and can be used hypodermatically. Dose, 2 grains (0.13 gm.). The salicylate contains about 6 per cent. and the benzoate about 50 per cent. of caffeine. In emergencies, caffeine is employed in two or three times the amounts stated.

Pharmacologic Action

Alimentary Tract

The taste is bitter. There is no direct action upon the tissues, but through nervous effects there may be hyperacidity and nausea.

Absorption is fairly rapid from the stomach and intestines. Cerebral stimulation from stomach doses is evident in from one-half hour to one and one-half hours.

Nervous System

Coffee and tea are so much used as beverages that their stimulating and nervous effects are well known to-the laity. These effects are of importance not only in the medicinal use of the drug, but also because of overindulgence in the beverages.

Cerebrum

After a fair dose of caffeine the mind becomes more alert, the attention keener, and the spirits brighter; or a state of drowsiness and inattention will be changed to one of wakefulness and brightness and activity. In other words, there is a real stimulation of the intellectual functions, especially those of reason, judgment, will, and self-control, the highest functions of the mind. At the same time the perceptions are more acute, the appreciation of pain is heightened, and, as shown by the esthesiometer, the sense of touch is more discriminating. Kraepelin found that the reception of sensory impulses and the association of ideas are facilitated, but the transmission of thought into action is retarded. This is because of the intervention of judgment. Caffeine also stimulates the motor areas of the brain, as indicated in a dog by the greater motor response to a given electric stimulus of the exposed motor area, and as shown in man by increased activity of voluntary motion. So caffeine is a true stimulant of the intellectual and motor centers of the cerebrum. It is directly antagonistic, in its cerebral effects, to alcohol. Doses of 8 to 15 grains (0.5 to 1 gm.) given to students produce overexcitability, agitation, and inability to concentrate.

Hollingworth, in his laboratory of psychology at Columbia, experimented on 6 assistants and 16 students for a period of forty days. He used capsules of citrated caffeine, with capsules of sugar of milk as controls. None of the subjects knew which of these was being taken. He made 76,000 measurements and 800 efficiency curves, with and without caffeine. Of the citrated caffeine, which is of 50 per cent. strength, 1 to 4 grains produced slight nervousness, not noticeable until several hours after the dose. There were increased speed and accuracy of movement, beginning in about an hour and lasting about four hours. Six grains produced marked unsteadiness.

In typewriting, small doses increased, and doses above three grains retarded, the speed; but the quality of the work, even with the larger doses, was superior to that of the same subjects on control days. There was no fatigue reaction to the extra work.

In calculations, there was marked increase in ability, the stimulation beginning in about one hour and lasting several hours. The morning following the experiment showed without exception a clear improvement over the work of the morning preceding the experiment.

In sick people, the condition of wakefulness and keener perception brought about by caffeine is usually highly undesirable; and in habitual insomnia one of the first things to look out for is that the patient shall not take tea or coffee toward evening.