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CAFFEINE AS AN ANTIDOTE
IN THE
0X50110115
BY
HENRY FRASER CAMPBELL, A. M., M. J).,
FORMERLY ONE OF THE VICE-PRESIDENTS OF THE AMERICAN MEDICAL ASSOCIATION; MEMEE
  OK THE BIOLOGICAL DEPARTMENT OF THE ACADEMY OF NATURAL SCIENCES OF PHILA-
      DELPHIA ; AND PROFESSOR OF SPECIAL AND COMPARATIVE ANATOMY
         I.V THE MEDICAL COLLEGE OF GEORGIA (AUGUSTA).
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          $agnsta, $wrp:
STEAM POWER PRESS OF THE CHRONICLE <fe SENTINEL.
            I860. 
 
From Southern Medical & Surgical Journal, May, I860.
               CAFFEINE.

   It is the design of the present brief communication, to call
the attention of the profession to an important, and we think,
most valuable application of Caffeine, as illustrated in a case
of extreme narcotism from the effects of Opium.
   Our knowledge of the  vegetable  alkaloids, and indeed, of
the Avhole subject of Organic Chemistry, is of comparatively
but recent date.   In the  year 1817, Terturner,  a German
Apothecary, having announced the existence of Morphia, the
spirit of investigation was immediately aroused, and the study
of every class of organic bodies has become the favorite occu-
pation of the chemist,  and has  yielded  him a treasury of the
most valuable results.  This process  of investigation  is  still
ardently pursued, and, every  day, some neAv organic compound
is being added to  the already lengthened list.
   "The alkaloids as a class," says  Dr. Parrish, "are the most
powerful  of  organic principles, displaying their effects espe-
cially on the nervous  system, which they so forcibly impress
as to constitute, many of them, virulent poisons; a feAV, Iioav-
ever, seem nearly destitute of active properties.  They all
contain nitrogen, and by destructive distillation, or by treating
with alkalies, evolve ammonia; they evince  their alkalinity
by restoring the color  of reddened litmus, and though not
always  crystalline or even solid, they combine with acids  to
form definite  salts which  are  crystalline;  they also, like the
alkalies proper, form double salts with bichloride of platinum."
   Most of the alkaloids are said to be but sparingly soluble  in
water, but they dissolve readily  in  alcohol,  especially with
heat.  Ether, the essential oils, and chloroform, dissolve most
of them, and almost all of them are  soluble in benzine.  " They
are all precipitated from solution, whether alone or combined
with salts, by tannic acid, which is hence,  when taken  imme-
diately, one of the best chemical antidotes for them ; they are
precipitated by alkalies."*
  These principles exist in  many plants, but not in a free
state, being generally combined with some peculiar vegetable
  *See Introduction to  Practical Pharmacy, by Edward ParYish.  Philad. 1851) 
4
 acid*   u All really poisonous plants are believed to contain an
 alkaloid or neutral characteristic principle,  except, perhaps,
 those feAV acrid poisons which owe their activity to resins."f
 To the presence of this  neutral principle many of our most
 valuable remedial  agents, especially in the vegetable king-
 dom,  owe all their activity, and by  it the phenomena they
 evoke from the animal economy is characterized.
   Whatever may be the  peculiar property of the crude vege-
 table,  whether potent for good or  for  evil,  that property is
 ever found to exist in a higher degree of intensity in its alka-
 loid representative; hence, of late years, since these princi-
 ples are becoming better knoAvn  to the Medical Profession,
 many  of them have entirely displaced as remedial agents,
 their more bulky sources on  account of their far greater
 potency and unmixed action. Thus quinia and its salts have en-
 tirely replaced, as an antiperiodic, the weaker and more bulky
 Peruvian bark, while the salts of morphia are rapidly supply-
 ing the place of all the other preparations of opium, and, except
 for the  intensity  of  their  action, strychnine and  atropine
 would long ago have driven all the other preparations of nux
 vomica  and  of belladonna, out of the catalogue of remedial
 agents.
   For a long period it has been well known to the profession,
 and  even in domestic life, that coffee,  Coffea  Arahica, pos-
 sessed virtues as  a stimulant of a  most valuable, and at the
 same time, of a peculiar kind.  In the London Medical Times
 & Gazette, of June, 1855, Dr. Julius Lehman has shown that
 coffee  is  powerful as a  stimulant in increasing the nervous
 energy, and that it also retards the metamorphosis of the tis-
 sues.   It is further considered that one  of the  physiological
 effects of coffee is to lessen the elimination of urea. Prominent
 among the alleged effects of coffee is its antisoporific power,
 or that  of inducing wakefulness when taken in large quanti-
 ties,  or by persons  unaccustomed to its use.   With this effect
 every one is  familiar who has  ever indulged in this common
 beverage.
  The  therapeutic applications of coffee in the form of infu-
sion  or decoction,  have been  various and long known to the
Profession.  It has been highly recommended as a remedy in
Cholera Infantum*; it is said to quiet nausea in many cases of
irritable stomach, a fact which we have ourself verified;  its
  jibid.
  *Dr. Pickford.  London Medical Gazette, Nov. 24, 1848.
  fSee Materia Medica and Therapeutics, by T\ D. Mitchell, M. D., to. 
5
use is prophylactic as well as curative in intermittent fever—
it has long been a valued remedy with some asthmatics—is
said to be one of the best agents for overcoming the effects of
alcoholic liquors—has been, from time immemorial, the favor-
ite beverage of opium-eaters, and is  frequently administered
to counteract the  effects of  this and other narcotic poisons.
The use of coffee for this purpose was  common some  forty
years ago  in  this country, and several  of  the  theses of the
University of  Pennsylvania,  on the  subject, were  printed.
Very strong decoctions,  without sugar or milk, Avere recom-
mended for this purpose. All opium-eaters are said to be great
coffee-drinkers.  Beaujour,  in  his work on Greece, gives an
account of an opium-eater who drank "more  than sixty cups
of coffee a day, and smoked as many  pipes.   All this was de-
signed to counteract the pernicious action of the opium."f
   In the Edinburgh Medical & Surgical Journal for January,
1842, a case of poisoning is reported,  caused by one and a
quarter grain   of sulphate of  morphia, equal  to seven and a
half grains of opium.  The cure was effected by gill doses  of
strong decoction  of coffee frequently administered.  Were it
necessary, we could easily adduce many more witnesses of the
therapeutic application  of coffee, but the above is sufficient to
show that it has been long known as a powerful agent in many
diseases, and further, that it has been fully recognized as a val-
uable means of counteracting the effects of opium.  We have
for years been in the habit of giving strong doses of the decoc-
tion of coffee in cases of over-doses of opium, and have seldom
treated a case  without applying it—after other and more effi-
cient remedies, as the  stomach-pump,  emetics,  &c,  have
emptied  the stomach—to re-animate  the patient and to over-
come drowsiness.
   As we have just said, whatever may be the peculiar medi-
cal or physiological action of any vegetable medicinal agent,
its alkaloid representative has been generally found to exer-
cise  that influence in a far  more efficient manner than the
crude source from which it was obtained.  This is thought to
be eminently the case, with regard to Caffeine, the alkaloid
active-principle of coffee.
  There are several vegetable  alkaloids which are said to be
identical with Caffeine, both in their chemical constitution and
in their effects on the animal economy. Theine obtained from
Tea, and Guaranin, from the Guarana—Paullina Sorbilis*—
^According to Von Martius, an extract is prepared in Brazil from Paullina 
6
are each said to possess virtues which, in no respact, vary in
their effects from that of Caffeine.
  " Caffeine is procured by exhausting bruised coffee by  two
successive portions of hoiling water, uniting the infusions; ad-
ding acetate of lead to precipitate the principles which accom-
pany the caffein ;  filtering and decomposing the excess of ace-
tate  of lead in a filtered liquor, by sulphuretted hydrogen;
concentrating by evaporation and neutralizing with ammonia.
The Caffein is deposited in  crystals, upon cooling, and may be
purified  by  re-dissolving in Avater, treating with animal char-
coal and evaporating."f  It presents itself in the form of long,
silky needles; is fusible, volatile and soluble in water, alcohol
and  ether.
  Phobus is inclined to doubt "whether caffeine is of the im-
portance that  has been assigned to it;  but Von Falck, from
much observation, ascribes to  it a highly powerful and even
poisonous action.   Experiments  on the loAver  animals have
been made  with  caffeine by several physiologists;  Albers of
Bonn, produced tetanic phenomena by its administration  to a
frog, and the same  symptoms were induced  by inserting a
solution of  the citrate  of caffeine under the skin of the thigh
of another frog." Mulder gave a grain of caffeine to a rabbit;
the  animal  ate but  little the next day, and aborted the day
after.   Lehman gave it in doses of from two to ten grains,
and reports§ that,  " it  caused violent excitement of the vascu-
lar and  nervous  systems, palpitations of the heart,  extraordi-
nary frequency, irregularity,  and often, intermission of the
pulse ;  oppression  of the chest, pains in the head, confusion of
the  senses, tinnitus aurium, scintillations before the eyes, sleep-
lessness, erections  and  delirium;  and,  in  all cases, there Avas
an increase in the amount of urea secreted."   It is extolled by
Hannon and  Eulenberg in the various forms of Hemicrania,
and has been frequently used for the same purpose, by the  prac-
titioners both of England and of this country.   Of the applica-
tion of caffeine as an antidote in the poisonous narcotism of
opium, we  have as yet seen  no published account, and henca
wo  h-ve deemed  the  subject  of  sufficient importance to call
tho n .ention of the profession to  the details of the following
 case:
 Sorbilis, which is known there under the name of " Guarana," which  is em-
 ployed successfully in  chlorosis, tedious convalescence, paralysis, the colliqua-
 tive diarrhoea of Phthisis, and in hemicrania.
                              See Dunglison;s New Remedies, p. 573-
   fDispensatory of the United States, 10th ed., p. 1318.
   §Physiological Chemis+ry. 
7
Extreme Narcotism of Opium promptly relieved hy Artificial
     Respiration and the administration  of Caffeine,
                       hy Injection.

  Monday, Oct. 10th, 1859, 8 o'clock, P. M.—We are called in
haste to Mr. E. H. T., aged 24 years, who, it was said, had taken
laudanum, and  was in imminent danger from the effects of the
drug.  We found the patient in the clerk's office of one of the
hotels of this city.  He Avas lying on a sofa with his head sup-
ported in  the lap  of a friend.  His respiration Avas very slow,
though not counted at  the time—pulse full, but of nearly nor-
mal frequency—he  was  completely  insensible—tongue and
lips purple, and  muscular  system  greatly relaxed.   It was
positively known that he had taken, in a fit of  temporary de-
pression, over one ounce and a half of laudanum, nearly an
hour before the time of the  present visit.
  The condition of the patient Avas so  alarming that we hegan
the treatment by the pouring of cold Avater on the head till the
stomach-pump  could be applied—for on attempting to intro-
duce the  tube into the oesophagus,  respiration appeared to
cease  altogether—the  entire muscular system Avas  so com-
pletely relaxed that the tongue hung  out of his  mouth, and
was pushed about by the end of the stomach-tube, in certain
positions,  folding back into the fauces,  and  apparently ob-
structing respiration. The attempt to use emetics was of course
out of the question.  The  continued use of ice-water upon the
head, and the  occasional  resort to  artificial respiration, in a
short time improved his condition a little—a very little—and
Ave were  Avilling  to introduce the stomach-tube.   This was
effectually applied; large quantities of tepid water being re-
peatedly introduced into the stomach and again pumped out.
Laudanum Avas detected both by its odor and color in the fluid
first discharged from the stomach.  At the end of an hour, his
condition  becoming apparently more urgent than before the
use of the stomach-pump,  he was taken from the clerk's office
to a room on the second floor of the hotel, where he was un-
dressed and placed in bed, and the application of ice-water to
the head was resumed.
  12 o'clock, midnight.—The condition of the patient was now
decidedly worse than  it had been at  any previous time; the
surface Avas cold, and purplish from imperfect aeration  of the
blood,  the muscular system, if possible, more relaxed than
ever, the  respiration, fearfully slow,  Avhen counted,  by the
watch, Avas found  to be hut four to the minute.   The intervals 
between the  inspirations  were now irregular, and each time
we had to  resort to shaking and slapping the patient to pro-
voke the automatic action of the respiratory muscles, and to
raising him up suddenly to the sitting posture, with the same
object.   The tongue had to be constantly pressed forward with
the fingers to prevent its falling  back and obstructing the
opening of the glottis.   The imperfect and irregular action ol
the heart became now more alarming than ever. It Avas found
that, in the reclining position, this  symptom of the case was
more alarming than when the patient was placed in  the sitting
posture.  Several times the intervals between the beats of the
pulse led  us  to  fear that the patient had expired, but on ele-
vating him, the action of the heart became more regular.  He
was now kept in  the elevated position, and not allowed to
recline except for a moment at a time, for fear that he would
die immediately.  Ceaseless efforts were now necessary on the
part of his attendants to provoke the respiratory movements.
Surrounded by his friends, several of whom were remarkably
self-possessed and indefatigable, not a moment was allowed to
pass without some effort, as by shaking, compressing the chest,
&c, to excite  inspirations.   Xo time Avas noAV to be lost—but
our best efforts at exciting respiration began iioav to fail to
have any effect,  and it Avas evident that  artificial respiration
was now, the only possible hope for the patient. This measure,
under  the  circumstances, was  a natural suggestion,  but  for
reasons sufficiently apparent, it seemed  impossible to  carry it
out in the present case;  most of the ordinary means of effect-
ing artificial  respiration seemed to us  impracticable, on ac-
count of the  delay involved  in their performance, and Dr.
Marshall Hall's "Ready  Method"  involved  the  horizontal
position, in which  situation, it was clear to the minds of all
present, the patient would die immediately.
       Artificial Respiration in the Sitting Posture.
  1 o'clock.—Under these circumstances, we devised a method
of artificial respiration  which was well adapted to  the condi-
tion of the  patient—indeed, the only one possible—and which
we do not recollect  to have seen reported any where in  the
writings of any one on this subject.
  The  patient was supported in the sitting posture, by an
assistant kneeling on the beet at his back and holding his head
erect between his hands; two other assistants standing on each
side of the patient now took charge of an arm each, holding
he limb firmly at the elbow and upper part of the forearm ; 
9
the tongue was now pressed doAvn by the handle of a spoon,
or the fingers introduced into the mouth ;  the assistants hav-
ing  charge of  the arms, were  now  directed to elevate  these
limhs simultaneous^, carrying them above the head at an angle
of about forty-five degrees, and dragging upon them so as to
slightly lift the patient; the arms were then depressed and
brought down close against the sides of  the Thorax so as to
compress the  chest.
  The effect  of these movements Avas the folloAving:  At each
attempt at lifting the body by the arms in this way, forcible
traction outwards Avas made on the walls of the chest, through
the pectorales major and minor muscles, the serrati and parts
of the tAvo latissimi dorsi muscles—giving rise to expansion of
the Avails of the thorax ; the air was thus caused to enter for-
cibly into the lungs, and thus inspiration was  completed.
The  arms were  then brought  steadily down,  and  pressed
against the  sides of the  thorax and abdomen—compressing
them and expelling the air forcibly from the lungs and effect-
ing expiration*
   Under the use  of the artificial  respiration, the appearance
of the patient Avas much improved.  The color was restored
to the face, the lips became redder, and the countenance more
natural, though the relaxation of the muscular system was by
no means lessened; if the  head was left unsupported for an
instant, it  fell  forward as  suddenly and  forcibly as that of  a
dead man.  The  artificial movements Avere continued for more
than an hour, and though  the   color of the patient Avas im-
proved  and the heart's action became normal, still when they
were omitted, there was found no improvement in the natural
respiration, these being still, but four times in a minute, as
before artificial respiration was applied.
  We noAv felt the necessity of adopting some means of intro-
ducing  a stimulant  or anti-narcotic  agent into  the system.
Strong Coffee naturally  presented  itself to our mind, but the
only preparation we could obtain at that time, Avas a rather
weak infusion left from the supper at the hotel. It was clearly
impossible for  the patient to swalloiu anything, and we did
not think it  advisable  to  run  the risk of introducing  the
stomach-tube in his present condition; we therefore called for
a syringe, but the weakness of the  coffee  caused us to hesitate
about using it, when, fortunately, the idea of Caffeine occurred

  *A more extended description of this "Natural method of Artificial Respira-
tion"  will be given hereafter. 
10
 to us, and  we  sent immediately for that preparation.  The
 artificial respiration was then energetically resumed, in order
 to prepare the patient for being placed in the horizontal posi-
 tion.  A small quantity of the Caffeine was rubbed upon the
 tongue and to the  inner surface of each  cheek.  The patient
 was then laid upon his side, and an injection of the coffee with
 a large quantity {afterwards ascertained to he twenty grains)
 of the Caffeine, dissolved in it, was administrred hy the rectum,
 with a common syringe.  The patient was then immediately
 raised again to the  sitting posture, and the  artificial respira-
 tion resumed.
   In less than half an hour, we perceived that occasionally,
 between the artificial  movements, the patient would effect a
 natural inspiration—these became more frequent,  and soon
 rose to about eight in the minute.  He was then laid down
 and the artificial respiration omitted.  The assistants, however,
 Avere directed still  to  remain on the bed and to retain their
 hold on his arms, that they  might resume their efforts at any
 moment.  An hour had  not elapsed from the administration
 of the injection, when  the patient,  to the  astonishment of all
 present, forcibly jerked his left arm from the assistant! (which
 was the first action of the voluntary muscles he had performed)
 and immediately began to twist himself in bed, and told those
 about him, angrily, "to let him alone !"
   From this time,  he did not  again sink into the comatose
 state, and the relaxation of the muscular system did not  re-
 turn.  The respiration  became more and more natural, but he
 remained  drowsy, and efforts were continued occasionally to
 prevent his remaining too long asleep.
   The condition of  the patient during the remainder of  the
 night, (from 2 o'clock till daylight) was very peculiar;  his
 eyes were heavy, he seemed greatly inclined to sleep, and  oc-
 casionally would snore a  little, but yet he appeared  quite
 cognizant of everything going on around  him, and of all  the
 remarks made by his attendants; he had great repugnance to
 being held or touched.  During the earlier part of  the nar-
 cotism, one of his friends, a young man, tried the expedient of
 tickling him on the ribs and loAver part of the abdomen, with
 the  hope  of arousing him; then, the tickling had no  effect
whatever, but now, it seemed to produce the most painful  an-
noyance, and vexed him beyond all control.  The measure
was advised, nevertheless, to keep  him  from falling asleep.
He would  lay  apparently asleep, but before the hand could 
11
reach the surface, he seemed to be aware of the intention, and
would select the  offender  from  the whole crowd of his atten-
dants, and aim the most angry blows at him with great accu-
racy;  and,  finally,  on one occasion,  before he could be
restrained,  he  jumped out of bed and  followed him to the
head of the steps, threatening to shoot him if he thus annoyed
him again.*
   We left him at daylight.  His drowsiness at that time was
not very marked.
   11th.—We called at the hotel at 10 o'clock, A. M., to see
Mr. T., and were informed that he had "gone home to his
own residence, nearly a mile distant,  at the lower part of the
city."
   12 o'clock, M.—We were called in haste to  see  our patient.
Found him in a most excited condition ; he seemed somewhat
alarmed, his face was flushed, his eyes presenting  an  unusual
brightness;  he  complained  of  head-ache, great restlessness,
and the surface Avas covered with a profuse  perspiration ; the
pulse  was  full, quick  and frequent.   He stated that  he had
had an  alarming attack  of a nervous  character, AAThich he
referred to irregularity and palpitation  in  the  action of the
heart,*  This had subsided, hoAvever, after taking a stimulant,
and his condition was such as just described.  Prescribed the
application of cold  Avater  to  the  head, and  that he  remain
quiet at home till his excitement  had subsided.   He  rapidly
recovered and  was Avell in a feAV days.
   There is  but a single  additional remark which we Avould
desire to  make on  the effect of Caffeine, as observed  in the
foregoing case.  Mulder, as we  have  seen, gave this alkaloid
to rabbits, and the animals aborted on the second day after its
administration  ; Albers, in one series of experiments on frogs,
administered the agent by the stomach, and in another, intro-
duced it  into  the tissues  beneath the cutaneous surface—the
effect in both instances, Avas to produce a tetanic condition of
  We have been thus minute in the description of these latter manifestations
because this peculiar sensibility and irritability appeared to us to be the result
ot tbe Caffeine, and we think it important to relate every thing which evidenced
its influence on  the nervous system, when administered in such a large dose-
The irritability was not the ordinary itching of the skin following opium ; (he
had that too) but an intolerance of all impressions made on  the surface, accom-
panied with a singular watchfulness of the mind,  (considering  his tendency to
sleep) on certain subjects.  He  never, for a  moment, seemed to forget that he
was in danger of being: tickled, and on no occasion did he  mistake any other
necessary handling of his person for an attempt to annoy  him.  There was a
clearness of the mind in this respect, which was truly remarkable.
  *We would here state that we would not advise the administration of the Caf
feine in such large quantity, viz : xx grains, as we used in the above case.  Did
the occasion occur again, Ave should use repeated  doses of v or x grains, till the
desired effect was produced. 
12
the muscular system.   In our patient, the muscular relaxation
was extreme ;  his head would fall from side to side, his tongue
hung out of his mouth, in the prone position, and fell back into
the fauces, in the recumbent posture ; not a fibre in his entire
muscular system seeming to possess its normal tonicit}r.  And
yet, in less than an hour after the  administration of a very
large portion of Caffeine by the rectum, all  this had suddenly
disappeared, and  lie was in the  exercise of the most active
muscularity; pulling away from his attendants, pushing them
from his bed-side, jumping out of bed, and performing every
variety of movements in the most energetic and Avell co-ordi-
nated manner.   From this simple collocation of the experi-
mental facts of Mulder and Albers, and of the observed facts
presented by our case, there certainly appears to be a relation
between the  phenomena of the  one and those of the other
which has  a bearing on the muscular system.   Caffeine, it
would appear, then, somewhat in  the same manner as strych-
nine,  may be regarded as one of  our most efficient agents for
restoring mascular contractility, and for reviving the tonicity
of the muscular fibre.
  The principal object of the present report, however, is only
to extend the results of the above remarkable case, wherein the
antinarcotic effect  of the drug  had been very apparent;  and
we therefore desire  to dwell no longer on incidental physio-
logical phenomena.  If in Caffeine, so powerful an alkaloid—
possessing, in a concentrated form, all the antisoporific virtues
of Coffee—Ave have thus found an antidote for the narcotic ef-
fects of opium, and one which can be applied even in the most
extreme states, hy injection, Ave must feel that an important ear
tension of its application as a therapeutic agent, has been made,
and that many lives may be saved hereafter, by its use.  Reason-
ing from the result of a single case, it is true, however remarka-
ble that case may be, is, Ave are aware, always more or less un-
reliable ; but, with the most jealous interpretation of the phe-
nomena, as we observed them, we have  been  forced to the
belief that the means used  here,  acted  most powerfully, in
producing the favorable result.   Indeed, Ave have never wit-
nessed sequences after the administration of a medicinal agent,
which impressed us more fully with .the conviction of cause
and effect.  We would, however,  take occasion, in closing, to
urge the repetition of the administration of Caffeine in cases
of Opium-Coma, to a  sufficient number of the  many which
are daily occurring  under the eves of the Profession, in order
to prove or disprove the validity of our confidence in'the remedy