The symptoms and mode of action of opium have been long made the subject of dispute, both among physicians and toxicologists; and in some particulars our knowledge is still vague and insufficient.
Under the head of general poisoning, some experiments were related, from which it might be inferred that opium has the power of stupefying or suspending the irritability of the parts to which it is immediately applied. The most unequivocal of these facts, which occurred to Dr. Wilson Philip, was instant paralysis of the intestines of a dog, when an infusion of opium was applied to their mucous coat;[[1695]] another hardly less decisive was palsy of the hind-legs of a frog, observed by Dr. Monro Secundus, when opium was injected between the skin and the muscles;[[1696]] and a third, which has been remarked by several experimentalists, is immediate cessation of the contractions of the frog’s heart when opium is applied to its inner surface.[[1697]]
The poison has also powerful constitutional or remote effects, which are chiefly produced on the brain. Much discussion has arisen on the question, whether these constitutional effects are owing to the conveyance of the local torpor along the nerves to the brain, or to the poison being absorbed, and so acting on the brain through the blood. The question is not yet settled. It appears pretty certain, however, that the poison cannot act constitutionally without entering the blood-vessels; although it is not so clear, that after it has entered them, it acts by being carried with the blood to the brain. The newest doctrine supposes that it enters the blood-vessels, and produces on their inner coat an impression which is conveyed along the nerves.
According to the experiments of Professor Orfila, it is more energetic when applied to the surface of a wound than when introduced into the stomach, and most energetic of all when injected into a vein.[[1698]] The inference generally drawn from these and other analogous experiments[[1699]] is, that the blood transmits the poison in substance to the brain. They certainly, however, do not prove more than that the poison must enter the blood before it acts.
The old doctrine, that the blood-vessels have no concern with its action, and that it acts only by conveyance along the nerves of a peculiar local torpor arising from its direct application to their sentient extremities, has been long abandoned by most physiologists as untenable. But some have adopted a late modification of this doctrine, by supposing that opium may act both by being carried with the blood to the brain, and by the transmission of local torpor along the nerves. They believe, in fact, that opium possesses a double mode of action,—through sympathy as well as through absorption. It would be fruitless to inquire into the grounds that exist for adopting or rejecting this doctrine, because sufficient facts are still wanting to decide the controversy. So far as they go, however, they appear adverse to the supposition of a conveyance of impressions along the nerves, without the previous entrance of the poison within the blood-vessels. The difficulties, in the way of the theory of the sympathetic action of opium, would be removed by the doctrine of Messrs. Morgan and Addison. According to their views, the experiments, which appear at first sight to prove that this substance operates by being carried with the blood to the part on which it acts, are easily explained by considering that the opium makes a peculiar impression on the inside of the vessels, which impression subsequently passes along the nerves to the brain.[[1700]] But, as stated in the introductory chapter on the physiology of poisoning, this theory requires support.
The effects of opium, through whatever channel it may produce them, are exerted chiefly on the brain and nervous system. This appears from the experiments of a crowd of physiologists, as well as from the symptoms observed a thousand times in man. In animals the symptoms are different from those remarked in man. Some experimentalists have indeed witnessed in the higher orders of animals, as in the human subject, pure lethargy and coma. But the latest researches, among the rest those of M. Orfila, show that much more generally it causes in animals hurried pulse, giddiness, palsy of the hind-legs, convulsions of various degrees of intensity, from simple tremors to violent tetanus, and a peculiar slumber, in the midst of which a slight excitement rouses the animal and renews the convulsions. These symptoms are produced in whatever way the poison enters the body, whether by the stomach, or by a wound, or by direct injection into a vein, or by the rectum. In man, convulsions are sometimes excited; but much more commonly simple sopor and coma.
According to the inquiries of M. Charret, which were extended to every class of the lower animals, opium produces three leading effects. It acts on the brain, causing congestion, and consequently sopor; on the general nervous centre as an irritant, exciting convulsions; and on the muscles as a direct sedative. It is poisonous to all animals,—man, carnivorous quadrupeds, the rodentia, birds, reptiles, amphibious animals, fishes, insects, and the mollusca. But of its three leading effects some are not produced in certain classes or orders of animals. In the mammalia, with the exception of man, there is no cerebral congestion induced, and death takes place amidst convulsions. In birds there is some cerebral congestion towards the close; but still the two other phenomena are the most prominent.[[1701]]
It has been rendered probable, by what is stated above, that opium enters the blood. The question, therefore, naturally arises, whether its presence there can be proved by chemical analysis? But considering the imperfection of the processes for detecting it when mixed with organic substances, no disappointment ought to be felt if this proof should fail in regard to so complex a fluid as the blood. The only person who has represented himself successful in the search is M. Barruel of Paris. He examined the urine and blood of a man under the influence of a poisonous dose of laudanum, amounting to an ounce and a half; and procured indications of morphia in both. When three ounces of urine were boiled with magnesia, and the insoluble matter was collected, washed, dried, and boiled, in alcohol, the residue of the alcoholic solution formed a white stain, which became deep orange-red on the addition of nitric acid. The blood was subjected to a more complex operation. One pound and ten ounces of it were bruised in a mortar, diluted with two pounds of water, strongly acidulated with sulphuric acid, boiled, filtered, and washed. The filtered fluid was saturated with chalk, and the excess of carbonic acid driven off by heat. The fluid was then filtered again, and after being washed with water, was acted on by diluted acetic acid. The acetic solution left on evaporation a residue which was repeatedly acted on by alcohol; and the residue of the alcoholic solutions was treated with pure alcohol and carbonate of lime. The new solution when filtered and evaporated left several small white stains, which became orange-red with nitric acid.[[1702]] These results have been since contradicted by M. Dublanc. He in vain sought for morphia in the blood and urine of people who were taking acetate medicinally, or of animals that were killed by it.[[1703]] Barruel’s results are also at variance with some pointed experiments of M. Lassaigne, who could not detect any acetate of morphia even in blood drawn from a dog twelve hours after thirty-six grains were injected into the crural vein;[[1704]] nor any in the liver or venous blood of a dog poisoned with eight ounces of Sydenham’s laudanum.[[1705]]
In investigating the effects of opium and its principles on man, the natural order of procedure is to consider in the first place those of opium itself in its various forms.
The effect of a small dose seems to be generally in the first instance stimulating: the action of the heart and arteries is increased, and a slight sense of fulness is caused in the head. This stimulus differs much in different individuals. In most persons it is quite insignificant. In its highest degree it is well exemplified by Dr. Leigh in his Experimental Inquiry, as they occurred to a friend of his who repeatedly made the experiment. If in the evening when he felt sleepy, he took thirty drops of laudanum, he was enlivened so that he could resume his studies; and if, when the usual drowsiness approached, which it did in two hours, he took a hundred drops more, he soon became so much exhilarated, that he was compelled to laugh and sing and dance. The pulse meanwhile was full and strong, and the temporal arteries throbbed forcibly. In no long time the customary torpor ensued. The stimulant effect of opium given during a state of exhaustion is also well illustrated by Dr. Burnes in his account of Cutch. “On one occasion,” says he, “I had made a very fatiguing night march with a Cutchee horseman. In the morning, after having travelled above thirty miles, I was obliged to assent to his proposal of haulting for a few minutes, which he employed in sharing a quantity of about two drachms of opium between himself and his jaded horse. The effect of the dose was soon evident on both, for the horse finished a journey of forty miles with great apparent facility, and the rider absolutely became more active and intelligent.”[[1706]]