THE MECHANISM OF NARCOTIC DRUG ADDICTION-DISEASE
I have in previous chapters referred to what are known as “withdrawal
signs.” By this term has come to be known the manifestations displayed
by a sufferer from addiction-disease at such times as his opiate is
taken away or “withdrawn,” either totally or in part to such an extent
that its amount does not meet the requirements of his physical needs.
In observing opiate addicts over a length of time no one can escape the
recognition of a chain of constantly present physical manifestations
inevitably following the non-administration of the drug of addiction.
These may vary in priority of onset, in sequence, and in relative
violence of manifestation in different cases, but they are the
inevitable result of non-administration of opiate to an opiate addict.
I described them as follows in a paper on “Narcotic Addiction--A
Systemic Disease Condition,” which was published in the _Journal of
the American Medical Association_, February 8, 1913. “In a general way
they may be said to begin with a vague uneasiness and restlessness
and sense of depression; followed by yawning, sneezing, excessive
mucous secretion, sweating, nausea, uncontrolled vomiting and purging,
twitching and jerking, intense cramps and pains, abdominal distress,
marked circulatory and cardiac insufficiency and irregularity, pulse
going from extremes of slowness to extremes of rapidity with loss
of tone, facies drawn and haggard, pallor deepening to greyness,
exhaustion, collapse, and in some cases death.”
These manifestations have been noted in various ways and to various
extents and have been casually commented upon by most writers of the
past. The conception of drug addiction as a “habit” has, however, in
the past so overwhelmingly dominated the attitude of writers both
medical and lay, that consideration of withdrawal signs as physical
phenomena, and the analysis of their origin and mechanism on the basis
of physical disease and constant body reaction has received all too
little attention. The tendency has been to casually regard or belittle
them as a part of the essential picture of narcotic addiction, and to
place overwhelming emphasis upon mental desire as an explanation of the
drug addict’s inability to discontinue the administration of opiate
drugs. That these physical manifestations have had such incidental
place and consideration in the general handling of the narcotic
addict and in the consideration of the drug problem is to my mind the
basic cause for past failure. Non-appreciation of them unquestionably
explains in part the almost uniform lack of success which attended my
own earliest efforts.
One of the obstacles to an appreciation of narcotic drug
addiction-disease has been the casual assumption on the part of the
average person, both lay and scientific, that opiate drugs act upon
the addict, and that he reacts to them similarly to the actions and
reactions in the non-addicted individual. Morphine action, however,
as commonly observed following therapeutic administration or in
experimentation upon un-addicted animals gives no conception of its
manifestations in the man or woman grown tolerant to its use. Many
of the actions and reactions of opiate upon the un-addicted are
practically lost in the addicted, and absolutely new reactions, unfound
in the un-addicted individual, become the dominating factors in the
opiate medication of the addict.
To some extent the fallacies connected with the general conception
of narcotic addiction have arisen from the mistaken application
to addicts of opiate experience, experimental or otherwise, of the
non-addicted. In the matter of sensations, for example, supposed
to follow opiate administration, and to the enjoyment of which is
widely attributed the addict’s indulgence--in practically none of the
opiate addicts, once tolerance and organic dependence are completely
established, do these sensations occur. The immediate effect of opiate
to the addict, depending upon the extent of tolerance, and the reaction
of the patient, in dosage not too much in excess of physical body need,
is apparently support to function, the restoration or maintaining of
normal circulation and nerve and glandular balance, prevention or
relief of the agonizing withdrawal pains and manifestations and of
impending collapse.
Opiate is used by the large majority of opiate addicts simply and
solely for its supportive action, and a certain amount for each addict
becomes as much of a definite need and a necessary and integral part
of his daily sustenance as food or air. The dream states and other
sensuous results, occasionally observed, are when they occur as part of
the minor toxic action of the drug, against which the developed addict
is nearly or completely immune, and to the experiencing of which very
few of the honest, innocent or accidental addicts have ever carried
their dosage. They are commonly found only in the opium pipe smokers,
an entirely different problem from that of the average narcotic addict.
As has been stated, it is a fact that for each addict, a definite
amount, varying with his condition of health, elimination, physical and
mental activity, etc., meets a definite body-need. On this amount he
can be put and kept in good physical and mental condition under normal
circumstances of environment, exertion, and general hygiene. Years
of efficient activity and upright responsible lives, accomplished by
well-known men and women, unsuspected addicts, bear witness to this
fact. An addict neither underdosed nor overdosed practically defies
detection. Less than the definite amount required for nervous and
glandular and circulatory support and organic balance deprives the
patient of reaction, places his vitality and energy far below par and
for a long time hinders his betterment. More than this amount displays
the inhibitory effects of opiates, locks up or slows secretions and
body functions, and causes malnutrition, autotoxemia, autotoxicosis,
and the consequent mental and physical deterioration commonly and
erroneously attributed to the direct action of opiate drug.
In 1912 I wrote that so far as I knew the symptomatology attending
insufficient supply of morphine (or other opiate) to an opiate
addict had never received the amount of detailed study and analysis
that it deserved and was not adequately interpreted. W. Marme had
attributed the symptoms of morphine addiction to the toxic action
of oxydimorphine. Rudolph Kobert, however, stated that Ludwig Toth
subjected Marme’s claims to subsequent testing and was unable to
confirm them, and that his own findings agreed with those of Toth. They
found that oxydimorphine was inert by subcutaneous injection and that
when thrown into the blood-stream it formed an insoluble substance
causing emboli, and so producing the symptoms observed by Marme.
Kobert seems to be in accord with the early findings of Magendie, that
oxydimorphine is non-toxic. The experiments of Faust on dogs concerning
increased power of the body to destroy morphine are well-known. It is
still a matter of scientific dispute as to what extent the body of the
opiate addict has developed the power to limit or destroy the poisonous
properties of opiates by the conversion of these poisons through
oxidation or other chemical action.
The explanation of tolerance and withdrawal phenomena on the basis of
something akin to an antitoxin or antitoxic substance circulating in
the blood of the addict, has also, like the oxidation explanation,
been a subject of controversy. Hirschlaff claimed to have produced
an antitoxic serum against morphine. Morgenroth failed to confirm
Hirschlaff’s findings, and argued against the existence of an
antitoxin. The animal experimental and laboratory work and findings,
however, of such men as Hirschlaff, Giofreddi and Valenti have helped
to influence the trend of modern thought towards what may be regarded
as the present strong tendency in scientific conception of the physical
mechanism of narcotic drug addiction-disease--an autogenous antidotal
or antitoxic substance.
A recent paper by DuMez of the United States Public Health Service
gives a comprehensive review of the work which has been done in
connection with the study of increased tolerance and withdrawal
phenomena, and shows conclusively the gradual inclination of modern
opinion.
There is considerable literature discussing various theories and
experiments and observations, which has, however, not had widespread
recognition.
REFERENCES
Bishop, E. S., “Narcotic Addiction--A Systemic Disease Condition,”
_Journal A. M. A._, Feb. 8, 1913.
Marme, W., “Untersuchungen zur acuten und chronischen
Morphinvergiftung,” _Deutsch. med. Wchnschr._ 9: 197-198.
Kobert, R., “Lehrbuch der Intoxikationen,” Stuttgart, 2; 995, 1906.
Toth, L., “Bemerkungen zur Erklärung der chronischen Morphium
Intoxikation,” Schmidt’s Jahrb. 229: 135, 1891.
Faust, E. S., “Über die Uraschen der Gewöhnung an Morphin” Arch. f.
exper. Path. u. Pharmakol. 44: 217-238, 1900.
Hirschlaff, L., “Ein Heilserum zur Bekämpfung der Morphinsucht und
Ähnlicher Intoxikationen,” _Berl. klin. Wchnschr._ 39: 1149-1152 and
1174-1177, 1902.
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.
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.
_Inhibition of Function_
What characteristic action exists in opiate or narcotic drugs which
gives them this power to establish the above described mechanism?
It seems to me that it is, above all, their power to inhibit body
function. They tend markedly to arrest metabolic processes. They
inhibit glandular activity. They inhibit unstriped muscle activity and
hence peristalsis. They, therefore, cause a slowing up of glandular
function and intestinal activity, and of elimination. This results in
an accumulation of opiate in the body. It is this constant accumulation
to which the body must become tolerant by the development of some
mechanism for its protection.
_Autointoxication and Autotoxicosis_
It is to the element of inhibition of function also that we must look
for explanation of what is by far the most important element in the
immediate picture presented by most individual cases. I refer to
autotoxicosis and to auto- and intestinal toxemia. The same power that
locks up within the body the opiate drug, locks up the toxic products
of tissue activity and tissue waste, of intestinal poisons and of
insufficient metabolism. Autotoxemia itself is markedly inhibitory in
its action, and contributes no little to its own increase and to the
further development of narcotic disease.
It is not at all impossible that any inhibiting poison constantly
present in the body will some day be found to establish a mechanism of
protection, similar to that of opiate addiction, and that some of the
states now popularly and loosely classified under the general head of
“autointoxications” will be recognized as really addiction-states, in
which the body has become progressively tolerant of its own poisons.
I believe that it can be demonstrated that some of the phenomena and
manifestations at times observed in chronically inhibited and autotoxic
individuals in whom there can be no suspicion of any opiate or narcotic
element are analogous to the phenomena of narcotic addiction mechanism.
It is not inconceivable that any inhibiting poison or toxin is capable
of producing its own addiction-mechanism, and it has seemed to me that
my own clinical familiarity with the action and reaction of narcotic,
inhibiting, or addiction-forming drugs and of addiction-mechanism upon
circulation, glandular and intestinal and other function has been of no
little assistance in the interpretation, control and remedy of other
chronic intoxications.
Upon the extent of inhibition of function and autointoxication,
therefore, depend some of the immediately predominating manifestations
in individual cases. They must be reckoned with and eliminated in
the measure of addiction-disease in the individual sufferer. In many
cases they contribute the immediate and compelling indications for
rational therapeutic endeavor. To a considerable extent they determine
circulatory efficiency and metabolic and glandular activity and
balance. They largely control physical tone and physical reaction.
Inhibition and intestinal and autotoxemia cause most of the physical
and mental deterioration, and much of the incidental symptomatology
so widely ascribed directly to narcotic drug effect. Upon the extent
of their presence, therefore, depends greatly the clinical picture in
the individual case. This doubtless accounts for the acidosis, noted
by Jennings and others, inasmuch as it has been definitely proved that
acidosis is commonly present in all conditions of functional depression
and exhaustion.
With inhibition and auto and other toxemia eliminated or reduced to
a minimum, the patient can go through many years, an apparent normal
man, well-nourished, reactive, in good physical tone, mentally sane
and physically competent. Under these conditions he shows practically
nothing abnormal as long as he gets properly administered, his
accustomed narcotic drug, in the amount of its minimum physical
requirement or body-need. His condition is often unsuspected by those
nearest and dearest to him, and the popularly held opinion that
narcotic addiction shortens life does not seem to be upheld by the
facts in his case. Such cases as his are far more numerous than has as
yet been realized.
In the types of narcotic addicts most widely recognized inhibition
of function and autointoxication is marked, and the opiate drug is
used in excess of body-need. The addict of this description becomes a
deteriorated wreck, requiring high doses of opiate for the satisfaction
of abnormal body-need, mentally and physically incompetent--the
generally accepted picture of the so-called “dope-fiend,” a
deteriorated, degenerated, malnourished wretch, degraded, avoided and
condemned.
Inhibition of function and autointoxication should not be vague
terms. They cause and are measurable by definite clinical evidence.
They display manifest phenomena and symptoms, and become increasingly
defined material entities as the clinician looks for them as such.
Much of inhibition of function and autointoxication and of their
manifestations, has been recognized and taught under their own
heading and in connection with conditions other than narcotic drug
addiction-disease. That the influence and importance of inhibition of
function and autointoxication in the development, and manifestations
of the narcotic drug addict has escaped general and widespread
recognition, is evidence of the small amount of unbiased clinical
study, and of analytical clinical interpretation of material physical
phenomena, hitherto accorded to narcotic drug cases.
I would not have it concluded that all symptoms and manifestations
arising in the handling of a drug addict are due to the factors and
elements I have discussed in this chapter. It must be always in the
mind of the intelligent and conscientious physician, that he has in his
care a human being with the same medical and psychical possibilities
that must be taken into careful and complete account, as in the
handling of any other sick person. There is an unfortunate tendency to
overlook concurrent, or complicating or pre-existing conditions in the
handling of the narcotic drug addict. These cases are often extremely
complex and difficult to analyze, and for adequate comprehension and
handling of them, the symptoms and manifestations they show should be
appreciated in their true origin and character as they occur in each
individual case.