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greater than subcutaneously. In making the tests on animals, they found that individuality, season, age, species, and certain pathological conditions caused variation in the toxic effect of the administered caffein. Low protein diet tends to decrease resistance to caffein in dogs, and a milk or meat diet does the same for growing dogs. Caffein is not cumulative for the rabbit or dog.

As a result of experiments on the action of caffein on the bronchiospasm caused by peptone (Witte), silk peptone, B-imidoazolyl-ethylamin, curare, vasodilation, and mucarin, Pal[265] concluded that caffein stimulates certain branches of the peripheral sympathetic and is thus enabled to widen the bronchi or remove bronchiospasm.

According to Lapicque[266], caffein produces a change in the excitability of the medulla of the frog similar to that produced by raising the temperature of the nerve centers. Schürhoff[267] has pointed out that the continued use of large quantities of caffein will produce cardiac irregularity and sleeplessness.

Cochrane[268] cited three cases where caffein was hypodermically administered in cases of acute indigestion, etc., and concluded that the cases prove that caffein, or a compound containing it as a synergist, does indirectly make the injection of morphia a safe proceeding, and directly increases the force of the heart and arterial tension. However, Wood[269] found that medium doses of caffein do not produce any marked rise in blood pressure, and cause a reduction in pulse rate. He attributes the contradictory results which prior investigations gave, to employment of unusually large doses and to inaccurate experimental methods.

Caffein was found by Nonnenbruch and Szyszka[270] to have a slight action toward accelerating the coagulation time of the blood, being active over several hours. It inhibits coagulation in vitrio. Its action in the body apparently rests on an increase of the fibrin ferment. There is no reason to believe that the behavior is dependent on a toxic action, but there is probably an action on the spleen; for in several rabbits from which the spleen was removed, no action was observed.

Experiments conducted by Levinthal[271] gave no positive information as to the formation of uric acid from caffein in the human organism. The elimination of caffein has also been studied by Salant and Reiger[272], who found that larger amounts of caffein are demethylated in carnivora than in herbivora, and resistance to caffein is inversely as demethylation, caffein being much more toxic in the former class. In a similar investigation, Zenetz[273] observed that caffein is very slightly eliminated from the system by the kidneys, and that its action on the heart is cumulative; therefore he concludes that it is contra-indicated in all renal diseases, in arterio-sclerosis, and in cardiac affections secondary to them. The inaccuracy of these conclusions regarding the non-elimination of caffein and those of Albanese,[274] Bondzynski and Gottlieb[275], Leven[276], Schurtzkwer[277], and Minkowski[278], has been shown by Mendel and Wardell[279], who point out that many of these experimenters worked with dogs, in which the chief end-product of purin metabolism is not uric acid, but allantoin. They observe that the increase in excretion of uric acid after the addition of caffein to the diet seems to be proportional to the quantity of caffein taken, and equivalent to from 10 to 15 percent of the ingested caffein. The remainder of the caffein is probably eliminated as mono-methylpurins.

Regarding the alleged cumulative action of caffein, Pletzer[280], Liebreich,[281] Szekacs[282], Pawinski,[283] and Seifert[284] all concluded from their investigations that the action of caffein is usually of brief duration, and does not have a cumulative effect, because of its rapid elimination; so that there is no danger of intoxication.

Dr. Oswald Schmiedeberg says:

Caffein is a means of refreshing bodily and mental activity, so that this may be prolonged when the condition of fatigue has already begun to produce restraint, and to call for more severe exertion of the will, a state which, as is well known, is painful or disagreeable.

This advantageous effect, in conditions of fatigue, of small quantities of caffein, as it is commonly taken in coffee or tea, might, however, by continued use become injurious, if it were in all cases necessarily exerted; that is to say, if by caffein the muscles and nerves were directly spurred on to increased activity. This is not the case, however, and just in this lies the peculiarity of the effect in question. The muscles and the simultaneously-acting nerves only under the influence of caffein respond more easily to the impulse of the will, but do not develop spontaneous activity; that is, without the co-operation of the will.

The character of caffein action makes plain that these food materials do not injure the organism by their caffein content, and do not by continued use cause any chronic form of illness.

According to Dr. Hollingworth's[285] deductions, caffein is the only known stimulant that quickens the functions of the human body without a subsequent period of depression. His explanation for this behavior is that "caffein acts as a lubricator for the nervous system, having an actual physical action whereby the nerves are enabled to do their work more easily. Other stimulants act on the nerves themselves, causing a waste of energy, and consequently, according to nature's law, a period of depression follows, and the whole process tends to injure the human machine." In not a single instance during his experiments at Columbia University did depression follow the use of caffein.

Of course, caffein, like any other alkaloid, if used to excess will prove harmful, due to the over-stimulation induced by it. However, taken in moderate quantities, as in coffee and tea by normal persons, the conclusions of Hirsch[286] may be taken as correct, namely: caffein is a mild stimulant, without direct effect on the muscles, the effect resulting from its own destruction and being temporary and transitory; it is not a depressant either initially or eventually; and is not habit-forming but a true stimulant, as distinguished from sedatives and habit-forming drugs.


Caffein and Mental and Motor Efficiency

The literature on the influence of caffein on fatigue has been summarized, and the older experiments clearly pointed out, by Rivers[287]. A summary of the most important researches which have had as their object the determination of the influence of caffein on mental and motor processes has been made by Hollingworth[288], from whose monograph much of the following material has been taken.

Increase in the force of muscular contractions was demonstrated in 1892 by De Sarlo and Barnardini[289] for caffein and by Kraepelin for tea. These investigators used the dynamometer as a measure of the force of contraction; however, most of the subsequent work on motor processes has been by the ergographic method. Ugolino Mosso[290], Koch[291]. Rossi[292], Sobieranski[293], Hoch and Kraepelin,[294] Destrée,[295] Benedicenti,[296] Schumberg,[297] Hellsten,[298] and Joteyko,[299] have all observed a stimulating effect of caffein on ergographic performance. Only one investigation of those reported by Rivers failed to find an appreciable effect, that of Oseretzkowsky and Kraepelin,[300] while Feré[301] affirms that the effect is only an acceleration of fatigue.

In spite of the general agreement as to the presence of stimulation there is some dissension regarding whether only the height of the contractions or their number or both are affected. As might be expected from the great diversity of methods employed, the quantitative results also have varied considerably. Carefully controlled experiments by Rivers and Webber[302] "confirm in general the conclusion reached by all previous workers that caffein stimulates the capacity for muscular work; and it is clear that this increase is not due to the various psychical factors of interest, sensory stimulation, and suggestion, which the experiments were especially designed to exclude. The greatest increase ... falls, however, far short of that described by some previous workers, such as Mosso; and it is probable that part of the effect described by these workers was due to the factors in question."

Investigations of mental processes under the influence of caffein have been much less frequent, most notable among which are those of Dietl and Vintschgau,[303] Dehio,[304] Kraepelin and Hoch,[305] Ach,[306] Langfeld,[307] and Rivers.[308] Kraepelin[309] observes: "We know that tea and coffee increase our mental efficiency in a definite way, and we use these as a means of overcoming mental fatigue ... In the morning these drinks remove the last traces of sleepiness and in the evening when we still have intellectual tasks to dispose of they aid in keeping us awake." Their use induces a greater briskness and clearness of thought, after which secondary fatigue is either entirely absent or is very slight.

Tendency toward habituation of the pyschic functions to caffein has been studied by Wedemeyer[310], who found that in the regular administration of it in the course of four to five weeks there is a measurable weakening of its action on psychic processes.

Rivers[311], who seems to have been the first to appreciate fully the genuine and practical importance of thoroughly controlling the psychological factors that are likely to play a rôle in such experiments, concludes that "caffein increases the capacity for both muscular and mental work, this stimulating action persisting for a considerable time after the substance has been taken without there being any evidence, with moderate doses, of reaction leading to diminished capacity for work, the substance thus really diminishing and not merely obscuring the effects of fatigue."


Effect of Caffein on Mental and Motor Processes
Schematic Summary of All Results
St.=Stimulation. 0=No effect. Ret.=Retardation.   PRIMARY EFFECT   Process Tests Small
Doses Medium
Doses Large
Doses Secondary
Reaction Action Time
Hours Duration
in Hours Motor speed 1. Tapping St. St. St. None .75–1.5 2–4 Coordination 2. Three-hole St. 0 Ret. None 1–1.5 3–4   3. Typewriting     (a) Speed St. 0 Ret. None Results show only in total
days' work   (b) Errors Fewer for all doses None Association 4. Color-naming St. St. St. None 2–2.5 3–4   5. Opposites St. St. St. None 2.5–3 Next day   6. Calculation St. St. St. None 2.5 Next day Choice 7. Discrimination reaction time Ret. 0 St. None 2–4 Next day   8. Cancellation Ret. ? St. None 3–5 No data   9. S-W illusion 0 0 0   General 10. Steadiness ? Unsteadiness None 1–3 3–4   11. Sleep quality Individual differences
depending on body weight
and conditions of
administration     12. Sleep quantity   2 ?     13. General health  

Subsequent to these investigations was that of Hollingworth[312] which is at once the most comprehensive, carefully conducted, and scientifically accurate one yet performed. He employed an ample

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