This explains the phenomena of the mathematical exactness with which the minimum daily need can be estimated under experimental conditions, and with which doses less than the amount of actual body need relieve existing withdrawal signs in definite proportion to the amount of opiate administered. In exact proportion as the drug of addiction is present in the body to neutralize or oppose some antidotal poison, is the patient free from withdrawal symptoms and from physical craving for the narcotic drug.
The development and existence of such mechanism in the body of the opiate addict is suggested also by the apparent continuance of tolerance to opiate existing after long periods without drug in individuals who had previously suffered from addiction-disease, and in the susceptibility of the former sufferer subsequent to the arrest of his physical need for opiate, to the re-establishment of that need by the subsequent administration of the drug.
Illustrative of this phenomenon is a case who, after about two years of relief from addiction-disease, developed pneumonia and to whom in delirium and threatened death, opiates were administered as unavoidable medication. After cessation of his delirium, he was dismayed to discover addiction-manifestations and body-need for opiate drug had been re-established. This history is one of a number in my possession, and has been verified.
The case demonstrating the longest persistence of susceptibility among my records, is that of a man in the early fifties who underwent an emergency operation for infected gall-bladder. A day or two following operation he developed excruciating pain in his right side just under the ribs. It had been necessary to administer opiates since a day or two before the operation. I was called in consultation for the purpose of determining the character and origin of the pain, and diagnosed a pleurisy, the pain of which subsided on the following day. Opiates were discontinued with a result of precipitating unmistakable withdrawal phenomena. To his great anger and surprise, I accused the patient of being an opiate addict. He indignantly declared that he had never used opiates in his life. Subsequent investigation with the aid of older members of his family disclosed a distinct and typical history of addiction manifestations following opiate administration in the course of treatment of a complicated fracture of his thigh in early boyhood. The drug had been withdrawn at that time and the addiction manifestations finally disappeared, he never having been aware of the facts. His reawakened addiction-manifestations were easily and quickly checked.
It is evident from many histories that large dosage robbed of or modified in its toxic effect, and even in the opiate manifestations usual in subjects who have never been made tolerant, and small dosage being sufficient to re-awaken physical need for opiates are conditions which do exist and persist for indefinite periods. The resemblance between this continued tolerance and the conditions existing in diseases which confer immunity and having a generally accepted antitoxin mechanism is too close to be ignored.
Evidence of a toxic substance in the body of a narcotic-addict is further presented by the similarity of the clinical pictures presented by these cases of acute opiate need and extremely severe cases of acute poisoning from materials such as the ptomains and some other poisons. Acute opiate need is clinically typical of intense suffering and prostration from the action of some powerful poison. Its symptoms cannot be due to opiate, for the reason that the administration of opiate relieves them, and relieves them exactly in ratio to the amount of opiate administered. They can be held at any given stage by gradation of the opiate dosage. Their manifestations, moreover, are exactly opposite to opiate effect. They are to my mind best explained as due to the action of some toxic substance, antidotal to opiate, prepared by the body for its protection in response to continued opiate presence in the body, as antitoxins are prepared for the neutralization of or opposition to the organic poisons of invading bacteria. The chemical or physical character or nature of such substance has not been yet determined.
The presence of such a substance would explain the establishing of tolerance, the manifestations following opiate administration and the apparent definiteness of the amount of opiate needed. It would explain the results of under-dosage and the results of over-dosage, and the practical non-interference with function or general health when a dosage is maintained exactly sufficient in amount to neutralize the effect of some exactly antidotal body or substance.
An antidotal substance would also explain the after effects of and the so-called “relapses” which occur after most of the cases treated by whatever method or procedure, without due appreciation and proper estimation of the clinical manifestations and indications of addiction symptoms and physical body need, and without due consideration of the patient’s reactive abilities and physical condition. These patients are in a condition of restlessness, discomfort, vague pains, mental and physical depression, lowered physical vitality and weakness. They have a sense of a physical lack of support. They cannot endure nor react to over-exertion, worry, strain, etc. This condition may persist for weeks and months after no opiate has been administered. The above seem to be mild withdrawal symptoms of an incompletely arrested addiction-disease mechanism and might be explained by a continued manufacture of small amounts-of antidotal toxic substance, causing a low grade chronic poisoning. They can be duplicated in active opiate addiction before withdrawal by administering an amount of opiate slightly below the amount of need and so leaving unneutralized a small amount of the antidotal toxic substance.
If continued production of a toxic antidotal substance, after discontinuance of the drug which called it into being is to explain the existence of the condition I have just described, the causation of this continued production must be accounted for. It is conceivable that in the development of addiction-disease mechanism a tolerance of and slowness to eliminate opiate or some product of opiate is acquired by all the cells of the body, perhaps especially by the liver, and that these tolerant and atonic cells are extremely slow of opiate elimination. Under this condition, a residue of opiate or some product of opiate capable of antidotal substance stimulation might remain unresponsive, or very slow of response, to ordinary cellular and other elimination. If this should prove to be the fact, it would account for a continued production of antidotal toxic substance, and might, moreover, in any given case, either before or after cessation of opiate medication, be one of the determining factors in the amount of antidotal substance produced, or, in other words, in the measure of the extent of body-need for opiate drug.