Chief among these agents are to be placed alcohol, opium, belladonna, stramonium, Indian hemp, tea, and coffee. It is true that the first two of these, when taken in large quantities, sometimes give rise to a comatose condition. This, however, as has already been shown, is not a consequence of an increased amount of blood in the brain, but results from the circulation in that organ of blood which has not been duly oxygenated by respiration. My experiments on this head have been many, and show conclusively that neither alcohol nor opium possesses any stupefying effect, if means be taken to insure the full aeration of the blood. If, however, these substances be administered beyond a certain limit, they so act upon the nerves which supply the respiratory muscles as to interfere with the process of respiration, and hence the blood is not sufficiently subjected to the action of the atmosphere. Unaerated blood therefore circulates in the brain, and coma--not sleep--is produced. No substance is capable of acting as a direct hypnotic, except that which lessens the amount of blood in the brain. In small doses alcohol and opium do this indirectly, through their stimulating properties exerted upon overdistended blood-vessels, as has been shown in regard to the first named in a case already cited; but they never so act upon the healthy brain. In the normal state of this organ their action in small doses is always that of excitants. The word “small” is of course used in a relative sense. What is a small dose for one person may be a large one for another, and _vice versa_. In this connection it is scarcely necessary to dwell at any length upon the wakefulness produced by delirium tremens from the excessive ingestion of alcohol or opium. In the _post-mortem_ examinations--four only--which I have made of individuals dying from this affection as the result of the immediate use of alcohol, the brain was invariably found congested. Either hyperæmia or its consequence, effusion of serum, is the ordinary pathological condition discovered in such cases. In regard to opium, most practitioners have doubtless noticed the effect which it and its preparations frequently produce in preventing sleep. I have known one dose of half a grain of opium keep a patient awake for three consecutive days and nights, during the whole of which period intense mental excitement was present. As is well known, the Malays, when they wish _to run amuck_, bring on the necessary degree of cerebral stimulation by the use of opium. During the condition thus produced insomnia is always present. It is certainly true, however, that in moderately large doses opium acts as a direct hypnotic, and the same may be said of other narcotics.