The condition of the principal markets of the world for this drug has
recently been exceptionally bad. That is, whether good coca was sought
for in the ports of Central and South America, or in London, Hamburg, or
New York, the search, even without limitation in price, was almost
invariably unsuccessful. Not that the drug, independent of quality, was
scarce, for hundreds of bales were accessible at all times; but the
quality was so poor as to be quite unfit for use. The samples, instead of
being green and fragrant, were brown and odorless, or musty and
disagreeable, at once condemning the lots they represented, to the most
casual observation, and yet the price was high enough to have represented
a good article. The best that could be done by the most careful buyers
was to accept occasional parcels, the best of which were of very inferior
quality, and therefore unfit for medicinal uses, and these at very high
prices. Coca is well known to be a very sensitive and perishable drug,
only fit for its somewhat equivocal uses when fresh and green, and well
cared for in packing and transportation. Very much like tea in this and
other respects, it should be packed and transported with the same care
and pains, in leaded chests, or in some equivalent package. It is very
well known that tea, if managed, transported, handled, and sold as coca
is, would be nearly or quite worthless, and therefore coca managed as the
great mass of it is must be nearly all of it comparatively worthless. If
used as tea is, this would probably soon appear; but when used as a
medicine which has been highly extolled and well advertised, it seems to
go on equally well whether of good or bad quality. It is pretty safe to
say that nineteen-twentieths of the coca seen in this market within the
past two years must be almost inert and valueless, yet all is sold and
used, and its reputation as a therapeutic agent is pretty well kept up.
At least many thousands of pounds of the brown ill-smelling leaf, and of
preparations made from it, are annually sold. And worse than this,
considerable quantities of a handsome looking green leaf, well put up and
well taken care of, have been sold and used as coca, when wanting in
nearly all its characteristics.
The writer for more than a year past has seen but one or two small lots
of moderately good coca, and in common with other buyers has been obliged
to buy the best that could be found to keep up his supply of the fluid
extract. Almost every purchase has been made on mental protest, and he
has been ashamed of every pound of fluid extract sent out, from the
knowledge that it was of poor quality; and there seems to be no more
prospect of a supply of better quality than there was this time last
year, because so long as an inferior quality sells in such enormous
quantities at good prices the demands of trade are satisfied.
Under this condition of the markets, the writer has finally decided to
give up making a fluid extract of coca, and has left it off his list,
adopting a fluid extract of tea instead, as a superior substitute, for
those who may choose to use it, and regrets that this course was not
taken a year ago.
The character of coca as a therapeutic agent is not very good. The florid
stories of a multitude of travelers and writers, up to and including the
testimony of Dr. Mantegazza, received a considerable support from so good
an authority as Sir Robert Christison, who reported very definite results
from trials made upon himself, and upon several students under his
immediate control and observation; and his results seem to have led to a
very careful and exhaustive series of observations at University College,
London, by Mr. Dowdeswell. This paper, published in _The Lancet_ of April
29 and May 6, 1876, pp. 631 and 664, is entitled "The Coca Leaf:
Observations on the Properties and Action of the Leaf of the Coca Plant
(Erythroxylon coca), made in the Physiological Laboratory of University
College, by G.F. Dowdeswell, B.A." The results of these investigations
were absolutely negative, and at the close of the work the investigator
says: "Without asserting that it is positively inert, it is concluded
from these experiments that its action is so slight as to preclude the
idea of its having any value either therapeutically or popularly; and it
is the belief of the writer, from observation upon the effect on the
pulse, etc., of tea, milk and water, and even plain water, hot, tepid,
and cold, that such things may, at slightly different temperatures,
produce a more decided effect than even large doses of coca, if taken at
about the temperature of the body."
Conflicting and contradictory testimony from competent authority is not
uncommon in therapeutics, and the reasons for it are well recognized in
the impossibility of an equality in the conditions and circumstances of
the investigations, and hence the general decision commonly reached is
upon the principle of averages.
There can hardly be a reasonable doubt that coca, in common with tea and
coffee and other similar articles, has a refreshing, recuperative, and
sustaining effect upon human beings, and when well cultivated, well
cured, and well preserved, so as to reach its uses of good quality and in
good condition, it is at least equal to good tea, and available for
important therapeutic uses. Mr. Dowdeswell supposed that he used good
coca, but it is very easy to see that with any amount of care and pains
he may have been mistaken in this. Had he but used the same parcel of
coca that Sir Robert Christison did, the results of the two observers
would be absolutely incomprehensible; and the results, in the absence of
any testimony on that point, simply prove that the two observers were
using a different article, though under the same name, and possibly with
the same care in selection. On Sir Robert Christison's side of the
question there are many competent observers whose testimony is spread
over many years; while on Mr. Dowdeswell's side there are fewer
observers. But there has been no observer on either side whose researches
have been anything like so thorough, so extended, or so accurate as those
of Mr. Dowdeswell. Indeed, no other account has been met with wherein the
modern methods of precision have been applied to the question at all; the
other testimony being all rather loose and indefinite, often at second or
third hands, or from the narratives of more or less enthusiastic
travelers. But if Mr. Dowdeswell's results be accepted as being
conclusive, the annual consumption of 40,000,000 pounds of coca at a cost
of 10,000,000 dollars promotes this substance to take rank among the
large economic blunders of the age.[9]
[Footnote 9: 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.]
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.
* * * * *