The testimony in regard to the effects of tea, coffee, Paraguay tea, Guarana and Kola nuts, is all of a similar character to that upon coca. Each of these substances seems to have come into use independently, in widely separated countries, to produce the same effects, namely, to refresh, renew, or sustain the physical and mental organism, and it was a curious surprise to find, after they had all been thus long used, that although each came from a different natural order of plants, the same active principle - namely, caffeine - could be extracted in different proportions from all. It is now still more curious, however, to find that for centuries another plant, namely coca, yielding a different principle, has been in use for similar purposes, the effects of which differ as little from those of tea, coffee, etc., as these do among themselves. Yet cocaine is chemically very different from caffeine, simply producing a similar physiological effect in much smaller doses. All these substances in their natural condition seem to be identical in their general physiological effect, but idiosyncrasy, or different individual impressibility or sensitiveness, causes a different action, as well in quality as in degree from the different substances, upon some persons.

In order to throw a little additional light on the comparative activity of the principal individuals of this group of substances, the following trials were made. It is generally admitted, and is probably true, that the same power in these agents which refreshes, recuperates, and sustains in the condition which needs or requires such effects also counteracts the tendency to sleep, or produces wakefulness when a tendency to sleep exists; and, therefore, if a tendency or disposition to sleep could be prevented by these agents, this tendency might be used as a measure of their effects when used in varying quantities, and thus measure the agents against each other for dose or quantitative effect. In this way the proposition is to first measure coca against tea, then coffee against guarana, and finally to compare the four agents, using pure caffeine as a kind of standard to measure by.

An opportunity for such trials occurred in a healthy individual sixty-five years old, not habituated to the use of either tea, coffee, tobacco, or any other narcotic substances, of good physical condition and regular habits, and not very susceptible or sensitive to the action of nervines or so-called anti-spasmodics. Quantities of preparations of valerian, asafoetida, compound spirit of ether, etc., which would yield a prompt effect upon many individuals seem to have little or no effect upon him, nor do moderate quantities of wines or spirits stimulate him. That is to say, he has not a very impressible nervous organization, is not imaginative, nor very liable to accept results on insufficient or partial evidence.

Fully occupied with work, both physical and mental in due proportion, for more than ten hours every secular day, when evening comes he finds himself unable to read long on account of a drowsiness supposed to be of a purely physiological character. With a full breakfast at about 7:30, a full dinner at about 2:30, and a light evening meal about 7, and no stimulants, or tea, or coffee at any time, he finds, as a matter of not invariable but general habit, that by half past 8 drowsiness becomes so dominant that it becomes almost impossible, and generally impracticable, to avoid falling asleep in his chair while attempting to read, even though ordinary conversation be carried on around him.

The first trial to combat or prevent this drowsiness was made with caffeine. The first specimen used was a very beautiful article made by Merck of Darmstadt, and after that by pure specimens made for the purpose, the two kinds being found identical in effect.

Commencing with a one grain dose at about 6:30 P.M., on alternate evenings, leaving the intermediate evenings in order to be sure that the nightly tendency still persisted, and increasing by half a grain each alternate evening, no very definite effect was perceived, until the dose reached 2½ grains, and this dose simply rendered the tendency to sleep resistible by effort. After an interval of three evenings, with the tendency to sleep recurring with somewhat varying force each evening, a dose of 3 grains was taken, the maximum single dose of the German Pharmacopoeia. This gave a comfortable evening of restedness, without sleep or any very strong tendency to it until ten o'clock. Without anything to counteract sleep, the rule was to read with difficulty by nine, without much comprehension by quarter past nine, and either be asleep or go to bed by half past nine. The 3 grain dose of caffeine repeatedly obviated all this discomfort up to ten o'clock, but did not prevent the habitual, prompt, and sound sleep, from the time of going to bed till morning.

This was the model established, upon and by which to measure all the other agents, and they were never taken nearer than on alternate evenings, with occasional longer intervals, especially when the final doses of record were to be taken.

The next agent tried in precisely this same way was coca; and knowing that the quality of that which was attainable was very low, the commencing dose of the leaf in substance was 2 drachms, or about 8 grammes. This gave no very definite effect, but 2½ drachms did give a definite effect, and a subsequent dose of 2½ fluid drachms of a well made fluid extract of coca gave about the same effect as 2½ grains of caffeine. Three fluid drachms of the fluid extract were about equivalent to 3 grains of caffeine.

Both the coca used and the fluid extract were then assayed by the modern methods, for the proportion of the alkaloid they contained.

The only assays of coca that could be found conveniently were those of Dr. Albert Niemann, of Goslar, given in the American Journal of Pharmacy, vol. xxxiii., p. 222, who obtained 0.25 per cent.; and of Prof. Jno. M. Maisch, in the same volume of the same journal, p. 496, who obtained 4 grains of alkaloid from 1,500 grains of coca, which is also about a quarter of one per cent. These assays were, however, very old, and made by the old process. The process used by the writer was the more modern one of Dragendorff slightly modified. It was as follows:

Thirty grammes of powdered coca, thoroughly mixed in a mortar with 8 grammes of caustic magnesia, were stirred into 200 c.c. of boiling water, and the mixture boiled for ten minutes. The liquid was filtered off, and the residue percolated with about 60 c.c. of water. It was then again stirred into 150 c.c. of boiling water, and was again boiled and percolated until apparently thoroughly exhausted. The total liquid, amounting to more than 600 c.c., was evaporated on a water-bath, commencing with the weaker portions, so that the stronger ones might be exposed to the heat for the shortest time, until reduced to about 20 c.c. This liquid extract was transferred to a flask, and vigorously shaken with 50 c.c. of strong ether. The ether was poured off, as closely as practicable, into a tared capsule, where it was allowed to evaporate spontaneously. A second and third portion of ether, each of 50 c.c., were used in the same way, and the whole evaporated to dryness in the capsule. A scanty, greenish, oily residue was left in the capsule, in which there was no appearance of a crystallized alkaloid. The capsule and contents were then weighed and the weight noted.

The oily residue was then repeatedly washed with small quantities of water, until the washings no longer affected litmus-paper. The oily matter adhered to the capsule during this process, no part of it coming off with the washing, and at the end of the washing the capsule and contents were again dried and weighed, and the weight subtracted from the original weight. The difference was taken as the alkaloid cocaine, and it amounted to 0.077 grm., equal to 0.26 per cent.

Several preliminary assays were made in reaching this method. Some authorities recommend the very finely powdered mixture of coca and magnesia, or coca and lime, to be at once exhausted with ether. Others recommend that the mixture be made into a paste with water, and after drying on a water-bath that it be then exhausted with ether. This is better, but neither of these methods were satisfactory.

Finally, 30 c.c. of a well made fluid extract of the same coca was thoroughly mixed with 8 grms. of caustic magnesia in a capsule, and the mixture dried on a water-bath and powdered. This powder was then exhausted, one part by ether and the other part by chloroform, exactly as in the method given, both parts giving very slightly higher results. As a check upon the results, the solution of alkaloid washed out was titrated with normal solution of oxalic acid.

From all this it would appear that this inferior coca of the markets, or rather the best that can be selected from it, yields about the same proportion of the alkaloid as was obtained by Niemann and Maisch, but it has been shown that, by the older processes of assay used by them, much of the alkaloid was probably lost or destroyed, and that much better results are generally obtained by the modern process.

Now, since 3 drachms of this coca, or three fluid drachms of its fluid extract, gave the same physiological, or perhaps therapeutical, effect as 3 grains of caffeine, and as the 3 drachms contained about 0.45 grain of cocaine, it follows that cocaine is about 6.5 times more effective than caffeine; but it also follows that the coca accessible, and even the very best coca, contains very much less of its alkaloid than those articles which yield caffeine do of that principle.

[1]From an "Ephemeris of Materia Medica, Pharmacy, Therapeutics, and Collateral Information." By Edward E. Squibb, M.D., Edward H. Squibb, S.B., M.D., and Charles F. Squibb, A.B.[2]An excellent summing up of the character and history of coca, from which some of the writer's information has been obtained, will be found in "Medicinal Plants," by Bentley and Trimen, vol. i., article 40.