Burmann[255] reported the volatile principle to have a reducing action on the hemoglobin; a depressing effect on the blood pressure; a depressant action on the central nervous system, disturbing the cardiac rhythm; and an action on the respiratory centers, causing dyspnea. The report of Sayre[256] regarding the minimum lethal dose of the concentrated combined active principles of coffee obtained from dry distillation is, for frogs, administered intraperitoneally and subcutaneously, 0.03 cubic centimeters per gram of body weight; for guinea pigs per stomach, 7.0 cc. per kilogram of body weight, and administered intravenously and intraperitoneally, about 1.0 cc. per kilogram. This evidence regarding the physiological action of caffeol can not in any wise be construed to indicate a harmfulness of coffee. The percentage of these volatile substances in a cup of coffee infusion is so low as to be relatively negligible in its action. And, again, the caffein content of the brew, as will be seen, tends to counteract any possible desultory effects of the caffeol. _General Physiological Action of Caffein_ More attention has been given to the study of the physiological action of caffein than to that of the other individual constituents of coffee. Since certain of the effects of coffee drinking have been attributed to this alkaloid, a brief presentment of the pharmacology of caffein will be given as an exposition of the many statements made regarding it. According to the _British Pharmaceutical Codex_[257]: Caffein exerts three important actions: (1) on the central nervous system: (2) on muscles, including cardiac: and (3) on the kidney. The action on the central nervous system is mainly on that part of the brain connected with psychical functions. It produces a condition of wakefulness and increased mental activity. The interpretation of sensory impressions is more perfect and correct, and thought becomes clearer and quicker. With larger doses of caffein the action extends from the psychical areas to the motor area and to the cord, and the patient becomes at first restless and noisy, and later may show convulsive movements. Caffein facilitates the performance of all forms of physical work, and actually increases the total work which can be obtained from muscle. On the normal man, however, it is impossible to say how much of the action on the muscle is central and how much peripheral, but, as fatigue shows itself first by an action on the center, it is probable that the action of caffein in diminishing fatigue is mainly central. Caffein accelerates the pulse and slightly raises blood pressure. It has no action in any way resembling digitalis; by increasing the irritability of the cardiac muscle, its prolonged use rather tends to fatigue than to rest the heart.