Gioffredi, C, “L’immunite artificielle par les alcaloides,” 28, 402-407, and 31, fasc. 3, 1897.
Valenti, A., “Experimentalle Untersuchungen über den chronischen Morphinismus; Kreislaufstörungen hervorgerufen durch das Serum morphinistscher Tiere in der Abstinenzperiode,” Arch. f. exper. Path u. Pharmakol., 75: 437-462, 1914.
DuMez, A. G., “Increased Tolerance and Withdrawal Phenomena in Chronic Morphinism, A Review of the Literature,” Jour. A. M. A., 72: 1069-1072, 1919.
My own present opinion and conception remains as expressed in a paper, “Narcotic Addiction—A Systemic Disease Condition,” written in 1912 and published in the Journal of the American Medical Association, Feb. 8, 1913, as follows, “It is my opinion that, however much increased oxidation aids in the handling of morphine, it is to the formation of an antitoxic substance that we must look for explanation of our clinical manifestations and for the classification of morphine-addiction as a definite medical entity. This opinion is based on certain clinical manifestations of morphine effect and the symptomatology attending insufficient supply of morphine to those addicted, on certain phenomena observed during and following treatment, on the persistence of tolerance and on the susceptibility of the cured patient to the re-formation of addiction.”
Before elaborating this conception of addiction-disease, I think it desirable to repeat the enumeration of the principal manifestations of “withdrawal” or body-need for opiate drug. In a general way, they may be said to begin with a vague uneasiness and restlessness and sense of depression and weakness; followed by yawning, sneezing, sweating, excessive mucous secretion, nausea, uncontrollable vomiting and purging or diarrhea, twitching and jerking, sometimes violent jactitation, intense muscular cramps and pains (described as if the flesh were being torn from the bones), abdominal pain and distress, marked cardiac and circulatory insufficiency, and irregularity (often with marked dyspnea), pulse going from extremes of slowness to extremes of rapidity, with lowered blood-pressure and loss of tone, facies drawn and haggard, pallor deepening to greyness, exhaustion, collapse and in some cases, death.
Essential Mechanism of Narcotic Drug Addiction-Disease
If such clean-cut, strikingly apparent, constant, and undeniably physical phenomena and symptomatology as I have described are to be adequately explained, there must be some physical mechanism, some definite body process working upon fundamental principles of disease reaction. They certainly are not psychiatric manifestations nor the expressions of habit, appetite, vice, nor morbid indulgence. Enjoyment of morphine for itself, even in such patients as have ever experienced such enjoyment, is lost long before the stage of rooted or completely developed addiction is reached. Physical results must be explained by physical cause.
Tolerance of and immunity to the toxic effects of narcotic drugs are primary and striking characteristics in the development of addiction. An antitoxin or antidotal substance is the recognized mechanism of their production in most diseases admittedly developing these characteristics. I have adopted the hypothesis, therefore, that an antidotal substance is manufactured by the body as a protection against the poisonous effects of narcotic drugs constantly administered. Such a substance, manufactured in the body, being antidotal to morphine, might well possess toxic properties of its own, exactly opposite in manifestation to those possessed by morphine and other opiates. Toxic substances exactly opposite to opiate in their action might readily account for the severe withdrawal signs, parallel in their extent to the extent of opiate insufficiency, and resembling in their characteristics the manifestations of acute poisoning.
A hypothetical antidotal toxic substance, manufactured by the body as a protection against the toxic effects of continued administration of an opiate drug, will therefore explain the well-known development of tolerance and immunity in these cases, and will account for the violent physical withdrawal signs. In a word, it will explain the disease fundamentals on a definite physical basis.
Such an hypothesis will explain the stages of development of addiction before outlined. In the stage of tolerance the antidotal toxic substance has begun to make its appearance in the body and to protect it against slight narcotic excess, but its manufacture is not sufficiently established to continue longer than necessary to neutralize the narcotic administered. In the stage of beginning addiction, or beginning narcotic-need, its manufacture has become more developed and more constant and proceeds for a longer time after the discontinuance of the narcotic drug. In the stage of fully developed addiction, or absolute narcotic need, the manufacture of the antidotal toxic substance has become practically an established pseudo-physiological body-process, and will continue long after the administration of the narcotic drug for reasons into which I have gone elsewhere. In other words, in narcotic drug addiction some antidotal toxic substance has become the constantly present poison, and the narcotic drug itself has become simply the antidote demanded for its control. In brief, fundamentally and basically, narcotic drug addiction is a condition presenting definite physical phenomena, symptoms, and signs, due to the presence within the body of some autogenous poison requiring narcotic drug for neutralization of it or of its effects.