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Present Status of Narcotic Addiction

With Particular Reference to Medical Indications and Comparative
Addiction Liability of the Newer and Older Analgesic Drugs

ON Mires eh) ter nme ALK :
f Le il A [ob&l (ld - a

VICTOR H. VOGEL, M.D.
HARRIS ISBELL, M.D.
and
KENNETH W. CHAPMAN, M.D.
Lexington, Ky.

Reprinted from The Journal of the American Medical Association
December 4, 1948, Vol. 138, pp. 1019-1026 Te

Coryricut, 1948, By
AMERICAN MEDICAL ASSOCIATION
535 North Drarsorn STREET
* Cutcaco 10, Itt.

Printed and Published in the United States of America

(
* Reprinted from The Journal of the American Medical Association
December 4, 1948, Vol. 138, pp. 1019-1026

Copyright, 1948, by American Medical Association

PRESENT STATUS OF NARCOTIC ADDICTION

With Particular Reference to Medical Indications and Comparative
Addiction Liability of the Newer and Older Analgesic Drugs

VICTOR H. VOGEL, M.D.

HARRIS ‘ISBELL, M.D.
and

KENNETH W. CHAPMAN, M.D.
Lexington, Ky.

When the Harrison Narcotic Act was passed in 1914 _
there were perhaps 150,000 to 200,000 narcotic addicts,
mostly women, in the United States.t Now, according
to a recent estimate by Mr. H. J. Anslinger, Commis-
sioner of Narcotics,” there is about 1 addict per 3,000
of population, or a total of approximately 48,000, mostly
men. This reduction in addiction has been largely due
to the vigorous enforcement of the Harrison Narcotic
Act and to federal facilities for the treatment of addicts.
Compared with the problems arising from the abuse of
drugs such as the barbiturates and alcohol, narcotic
addiction is not a great public health hazard. However,
to the person and his family, narcotic addiction is a
tragedy which often brings about complete ruin. With-
out the preventive influence of legal control and the
treatment of identified addicts, narcotic addiction would
spread somewhat like the infectious diseases which are
public health problems.

If one listens to the inveterate narcotic addict, the
question immediately arises as to why addiction should
be controlled and discouraged, since the addict describes

From the United States Public Health Service Hospital, Lexington, Ky.

Read in the General Scientific Meetings at the Ninety-Seventh Annual
Session of the American Medical Association, Chicago, June 22, 1948.

This article was edited previous to the date on which the Council on
Pharmacy and Chemistry announced in THE JOURNAL the addition of a
second ‘“‘e”’ in the spelling of “‘methadone.”’

1. Ko ‘Ib, L.: Drug Addiction as a Public’ Health Problem, Scient.
Monthly 48: 391 (May) 1939.

2. Anslinger, H. J.: Testimony Given Before the Subcommittee of
the Committee on Appropriations, House of Representatives, Eightieth
Congress, Second Session, Supplemental Federal Security Agency Appro-
priation Bill for -1949, Printed for the Use of the Committee on
Appropriations, Washington, D. C., Government Printing Office, 1948.
2

“God’s medicine” as the agent which makes him at
ease, contented, ambitious and of such improved eff-
ciency that he can compete on normal terms with his
fellowman. This effect is not seen in the majority of
cases. After mentioning the exceptional persons who
may adapt to life’s difficulties better with narcotic drugs,
Kolb said of morphine and morphine-like drugs *:

when taken in large doses, [they] sap the physical
and mental energy; lethargy is produced, ambition is léssened,
and the pleasurable feeling already described—that all is well—
makes the addicts contented. These various effects cause them
to pay less attention to work than formerly; consequently, they
tend to become idlers by this means alone. Those who depend
upon the illegitimate traffic are sometimes unable to work
because of discomfort and weakness due to insufficient narcotics,
and at other times they stay away from their work in order
to look for the drug. There are cases . . . who have gone
to distant cities regularly to get an ounce of heroin or morphine,
and others who have lost as many as a dozen jobs through:
neglecting work to meet their peddlers, or through lying in bed
in the morning instead of going to work because the dose that ©
would have put energy into them was not available. Often,
when these cases secure a supply, after their short periods of
deprivation, they take more than is actually necessary to keep
them comfortable. The result is that they alternate between
physical and mental irritability and physical and mental lethargy.
Both extremes make for emaciation, physical inefficiency, and
unusual mental reactions.

The dreamy satisfaction and the pleasurable physical thrill
produced by opium in many addicts in their early experiences
with it are of themselves forms of dissipation that tend to cause
moral deterioration. Addicts, as a rule, are compelled to asso-
ciate with persons of low moral character in order to continue
their addiction. Financial embarrassment resulting from idle-
ness or the high price of peddled narcotics impels them to beg
money from their friends, obtain it from members of their
families by subterfuge, or steal, in order to supply themselves
with drugs; they suffer in manliness through feeling what they
often consider the just contempt of the public; they suffer
through their constant fear of arrest, or because of a term in
the penitentiary served for having narcotics in their possession.
This train of events brings about unfavorable character changes
and gradual moral deterioration, and converts what might have
been fairly useful citizens into outcasts, idlers, or dependents.

In spite of the fact that there is no consistent organic
damage seen in the body following prolonged and exces-

 

3. Kolb, L.: Pleasure and Deterioration from Narcotic Addiction,
Ment. Hyg. 9: 699 (Oct.) 1925.
3

sive use of narcotic drugs, character deterioration is
real and great, as evidenced by the deliberate policy of
the Japanese in the late war to make addicts of large
segments of the alien populations under their control.

DEFINITION OF DRUG ADDICTION

Drug addiction may be defined as a state in which
a person has lost the power of self control with reference
to a drug and abuses the drug to such an extent that
the person or society is harmed. In the United States,
only derivatives of opium (including morphine, heroin,
dihydromorphinone hydrochloride [“dilaudid hydro-
chloride’ ], codeine and metopon), the morphine-like
synthetic drugs (including meperidine hydrochloride
[‘‘demerol hydrochloride’ |, methadon [amidone, “dolo-
phine,” 10820] and isomethadon), cocaine and mari-
huana are under control of the Harrison Narcotic Act
and similar acts. There are other drugs which, accord-
ing to our definition, are addicting, including the bar-
biturates, bromides, alcohol, peyote (mescaline) and
amphetamine, but none of these are subject to legal
control. However, users of peyote are eligible for treat-
ment at the federal hospitals for drug addicts.

Himmelsbach and Small‘ described addiction to
opium and similar drugs as embracing three intimately
related but distinct phenomena: (1) tolerance, (2)
physical dependence and (3) habituation.

Tolerance is defined as a.diminishing effect on repeti-
tion of the same dose of the drug or, conversely, a
necessity to increase the dose to obtain an effect equiva-
lent to the original dose when the drug is administered
repeatedly over a period of time. Physical dependence
refers to an altered physiologic state, brought about by
the repeated administration of a drug over a long period
of time, which necessitates the continued use of the
drug to prevent the appearance of the characteristic
illness which is termed an abstinence syndrome. Habit-
uation refers to emotional or psychologic dependence
on the drug—the substitution of the drug for other
types of adaptive behavior. Habituation is closely
related to a drug’s euphoric effect, i.e., relief of pain
or emotional discomfort.®

 

4, Himmelsbach, C. K., and Small, L. F.: Clinical Studies of Drug
Addiction: II. ‘‘Rossium”’ Treatment of Drug Addiction; with a Report
on the Chemistry of ‘“‘Rossium,’? Supplement 125 to the Public Health
Reports, United States Treasury Department, Public Health Service,
1937, p. 1.
4

The comparative importance of these three qualities
in the total picture of addiction is still a matter of
dispute. The role of tolerance in addiction is obscure
and difficult to evaluate. Tolerance, however, has been:
shown to develop to all morphine-like drugs. It is
empirically included as one of the qualities of the addict-
ing drug. Physical dependence has been regarded by
many persons, particularly by pharmacologists, as the
primary and only distinguishing characteristic of an
addicting drug. Other persons, particularly psychia-
trists, regard emotional dependence or habituation as
the all-important factor in addiction. Some have gone
so far as to claim that withdrawal symptoms are psychic
and not of physiologic origin. A view intermediate
between these two extremes is probably correct. Both
physical and ‘emotional dependence are important in
addiction to morphine. Wikler ® has shown that physi-
cal dependence on morphine and methadon develops
in the isolated segments of the spinal cord in chronic
spinal dogs, and also that physical dependence occurs
in chronic decorticated dogs. Wikler’s observation
proves beyond doubt that physical dependence is a real
physiologic entity and is not psychic in origin. On the
other hand, physical dependence does not explain why
addicts begin the use of drugs, continually increase
the dose and number of doses until they are dependent.
Nor does physical dependence explain why so many
addicts repeatedly relapse to the use of drugs long after
the withdrawal illness has subsided. Some addicts begin
to use drugs for the alleviation of pain caused by organic
lesions; others take up the habit to relieve emotional
tension ; all continue to use the drug because they enjoy
the sensation it produces when taken in amounts beyond
that necessary to alleviate or to prevent the appearance
of the withdrawal illness. -

Barbiturates fulfil all three criteria of addiction: tol-
erance is developed; habituation is developed; physical
dependence, although not seen as consistently as with
morphine, has been repeatedly observed among our
patients who have used barbiturates alone or with

 

5. Wikler, A.: Hindlimb Reflexes in Chronic Spinal Dogs During a
Cycle of Morphine Addiction, Federation Proc. 4: 141 (March) 1945.
Wikler, A., and Frank, K.: Tolerance and Physical Dependence in Intact
and Chronic Spinal Dogs During Addiction to 10820 (4-4-diphenyl-6-
dimethylamino-3-heptanone), ibid. @:384 (March) 1947, Wikler, A.:
Reactions of Chronic Decorticated Dogs During a Cycle of Addiction to
Methadon, ibid. 7: 265 (March) 1948.
5

morphine. If barbiturates are withdrawn abruptly from
patients who have been taking 12 grains (0./8 Gm.)
or more daily for several weeks, convulsions may
develop in three to four days and acute psychotic reac-
tions may be seen after seven to ten days. Both of
these conditions can be avoided by gradual reduction
of the daily dose of barbiturates over a period of
three weeks.

Bromide addicts show habituation but not physical
dependence, as demonstrated by the fact that withdrawal
is best accomplished abruptly and by elimination pro-
cedures. Tolerance to bromides is doubtful.

Amphetamine fulfils the most important qualification,
that of habituation, but neither physical dependence
nor tolerance develops. The best treatment is abrupt
withdrawal of the drug.

Cocaine produces habituation but does not induce
physical dependence or tolerance. Cocaine, when taken
intravenously, produces an orgastic sensation, and
addicts repeat their doses at very short intervals in
order to experience this feeling of ecstasy as often as
possible. As the dose is repeated, the toxic effects
of cocaine accumulate and the users have hallucinations
and paranoid delusions, which may be dangerous. The
toxic effects of cocaine are so unpleasant that there are
few pure cocaine addicts in the United States. Ordi-
narily the drug is used in conjunction with some
physiologic antidote, particularly morphine.

Marihuana causes a mild form of intoxication which
is popular among maladjusted adolescents and others,
including musicians. Neither tolerance nor physical
dependence develops with this drug. The greatest dan-
ger of smoking marihuana appears to be possible pre-
cipitation of disturbed behavior in persons with incipient
psychoses.*®¢

With alcohol, tolerance and habituation definitely
develop. It is possible that delirium tremens, alcoholic
“epilepsy” and other phenomena sometimes attributed
to toxic effects of alcohol represent abstinence syn-
dromes based on physical dependence on this drug.

6. (@) Wallace, G. B.: The Marihuana Problem in the City of New
York: Sociological, Medical, Psychological and Pharmacological Studies,
Lancaster, Pa., Jacques Cattell Press, 1945. (b) Reichard, J. D.: Some
Myths About Marihuana, Federal Probation, 10:15 (Dec.) 1946. (c)
Williams, E. G.; Himmelsbach, C. K.; Wikler, A.; Ruble, D. C., and
Lloyd, B. J.: Studies on Marihuana and Pyrahexyl Compound, Pub.
Health Rep. 61: 1059 (July 19) 1946.
6

ETIOLOGIC ASPECTS

Drug addiction should be regarded as a symptom of
a basic underlying personality maladjustment. These
personality disorders run the gamut of the standard
psychiatric nomenclature from the simple anxiety states
to the major psychoses. A vast majority of narcotic
drug addict patients are fundamentally emotionally
immature childlike persons, who have never made a
proper adaptation to the problems of living. Many: of
our patients are former alcoholic addicts who found
that narcotic drugs relieved their inner emotional ten-
sion as effectively as alcohol but, at the same time,
did not produce obvious signs of intoxication. After
changing from alcohol to narcotic drugs, alcoholic
addicts may be able, for a period of time, to deceive
themselves and their associates into believing that they
are making a satisfactory adjustment.

The kinds of personality disorders which underlie
drug addiction have been well described by Kolb 7 and
by Felix,’ who lists four general personality types.

The first group is made up of normal persons acci-
dentally addicted. It consists of patients who in the
course of an illness have received drugs over an
extended period of time and, following relief of their
ailments, have continued the use of drugs. These
persons are frequently termed “accidental” or “medical”
addicts. Such persons are regarded by some authors
as constituting a special group of addicts who are
different from those persons who began the use of
drugs as a result of association with persons who were
already addicted. In our experience, all “medical”
addicts have some fundamental emotional problem which
causes them to continue the use of drugs beyond the
period of medical need. There is, then, no basic differ-
ence between “medical” and “nonmedical” addicts
except in the mode of the original contact with drugs.
In persons with stable personalities, social pressure,
conscience and a well balanced emotional makeup
negate the pleasure produced by drugs sufficiently to
prevent their continued use. .

 

7. Kolb, L.: Types and Characteristics of Drug Addicts, Ment. Hyg.
9: 300 (April) 1925.

8. (a) Felix, R. H.: Some Comments on the Psychopathology of Drug
Addiction, Ment. Hyg. 28: 567 (Oct.) 1939; (b) An Appraisal of the
Personality Types of the Addict, Am. J. Psychiat. 100: 462 (Jan.) 1944.
7

The second group consists of persons with all kinds
of psychoneurotic disorders who, as Felix ** said, take
drugs to relieve whatever symptoms they may have.
The manifestation of the neurosis may be anxiety, an
obsession or compulsion or any of the great group of
psychosomatic disorders.

The third and largest group consists of psychopathic
persons, who ordinarily become addicted through con-
tact and association with persons already addicted.
They are generally emotionally undeveloped aggressive
hostile persons who take drugs merely for pleasure
arising from the unconscious relief’ of inner tension,
as shown by this statement of an addict:

I was always getting into trouble before I got on drugs—
never could seem to get comfortable; I had to go somewhere
and do something all the time. I was always in trouble with
the law. Some fellows told me about drugs and how good they
made you feel, and I tried them. From then on I was content
as long as I had my drugs—lI didn’t care to do anything but to
sit around, talk to my friends occasionally, listen to the radio,
and only be concerned with the problem of getting money for
drugs. This I usually did by picking pockets or other such
petty stuff.

The fourth and smallest group is characterized by
drug addiction with psychosis. The persons in this
group, many of whom have borderline mental illness
and sometimes frank mental illness, are seemingly able
to make a better adjustment while taking drugs. Some-
times it is difficult to establish the diagnosis and not
until drugs are withheld does the psychosis become
apparent.

There is a category of patients not included in the
aforementioned groups. Kolb* originally listed these
as patients with psychopathic diathesis. While it is
true that some of these exhibit much of the overt beha-
vior pattern of psychopathic persons, when studied care-
fully they usually fall into a milder behavior or character
disorder group, which has characteristics of both the psy-
choneurotic and the psychopathic groups. Included are
persons with severe dependency problems, withdrawn
schizoid types, emotionally immature adults, as well
as those suffering with the milder degrees of maladjust-
ment and inadaptiveness to the complications of living.
Felix ** stated that most of the persons falling into this
8

group were making a marginal adjustment to life before
becoming acquainted with narcotics. After their first
few experiences with narcotics they felt an exhilaration
and a sense of relief comparable to the solution of a
difficult problem or the shaking off of a heavy respon-
sibility. Many of them also felt an increase in efficiency
which, in some cases, appeared to have been actual
improvement. |

In general, persons who never have been able to
make a satisfactory adjustment to life, whose adaptive
patterns of behavior have been inadequate, frequently
find in morphine, much as the tired business man finds
in the preprandial cocktail, a means of return to “nor-
mal.” This is a false situation which may be recognized
by the tired business man but is not ‘recognized by
the drug addict. Our studies indicate that patients who
have made a marginal degree of emotional adjustment
to life, and then have begun to use drugs, lose some
of their normal adaptive patterns of adjustment. This
regression in personality represents the greatest danger
of drug addiction.

DIAGNOSIS OF OPIATE ADDICTION

The diagnosis of addiction is usually made by the
patient’s statement that he is addicted to and needs
drugs. At times, however, addicts attempt to conceal
their addiction and the diagnosis may be difficult. There
are no pathognomonic physical signs of addiction, but
emaciation, needlemarks and abscess scars are sugges-
tive. In some instances, none of these signs may be
present. Mlosis is not a reliable sign, as partial toler-
ance to the pupillary constriction caused by morphine
develops during addiction. Signs of intoxication, such
as ataxia and slurred speech, are seldom present unless’
the addicts are taking barbiturates or some other sedative
drug in addition to morphine. Meperidine hydrochlo-
ride addicts are likely to show pronounced dilatation
of the pupils and muscular twitching. Laboratory tests ©
for the presence of morphine or other drugs in the urine
furnish almost absolute evidence that the patient is
receiving drugs, but these tests are difficult to carry
out and ordinarily are not available. In questionable
cases, the only possible method of diagnosis may be
isolation of the patient from the source of drugs and
observation for signs of abstinence.
9

The signs of abstinence have been delineated best by
Himmelsbach and his co-workers. One must always
distinguish between the true signs of abstinence and
signs which are attributable to anxiety reaction or symp-
toms which are feigned in an effort to obtain drugs.
If morphine is abruptly withdrawn from a patient who
has been receiving as much as 4 to 6 grains (0.26 to
0.39 Gm.) daily for a period of thirty days or more,
few signs are seen in.the first eight to sixteen hours of
abstinence. The patient is likely to go into a restless
tossing sleep which lasts several hours. About fourteen
hours after the last dose of the drug, yawning, rhinor-

rhea, sweating and lacrimation are noticed. These mild -

signs increase in intensity during the first twenty-four
hours of abstinence; thereafter they become constant.
At this time, dilatation of the pupils and recurring
waves of gooseflesh appear. One must observe patients
carefully in order to detect these signs.

About thirty-six hours after the last dose, uncontrol-
lable twitching of the muscles occurs (the origin of the
term “kicking the habit”). Severe cramps develop in
the legs, abdomen and back; anorexia and insomnia
become prominent ; vomiting and diarrhea are frequently
seen. Rectal temperature rises about 2 degrees (F.) ;
respiratory rate rises to 25 to 30 per minute; systolic
blood pressure is usually elevated about 15 mm. of
mercury; caloric intake is sharply reduced; weight loss
averages 5 or 6 pounds (2.3 or 2.7 Kg.) a day. These
acute signs and symptoms reach their height forty-eight
hours after the last dose of morphine is taken and
-remain at a peak until seventy-two hours have passed.
They then gradually subside over the course of the next
five to ten days. Insomnia and changes in pulse rate,
body temperature and the hematocrit reading can be
detected for as long as three to four months after with-
drawal. A simple clinical method for grading the inten-
sity of abstinence is shown in table 1.

 

(2) Himmelsbach and Small.4 (6) Kolb, L., and Himmelsbach,
C. XK. Clinical Studies of Drug Addiction: III, A Critical Review of
the Withdrawal Treatments with Method for Evaluating Abstinence
Symptoms, Supplement 128 to the Public Health Reports, United States
Treasury Department, Public Health Service, 1938, p. 1. (c) Himmels-
bach, C. K.: Studies of Certain Addiction Characteristics of (a) Dihydro-
morphine (‘“Paramorphan”), (b) Dihydrodesoxymorphine-D (‘‘Desomor-
phone’), (c) Dihydrodesoxycodeine-D (‘‘Desocodeine’’), and (d) Methyl-
dihydromorphinone (‘“‘Metopon”), J. Pharmacol. & Exper. Therap. 673
239 (Oct.) 1939,

~~
10

The intensity of abstinence from morphine is
dependent more on the dose the addict has been receiv-
ing than on any other single factor.1° Mild grades of
abstinence may be detected in former morphine addicts
after the administration of as little as 20 mg. (% grain)
of morphine four times daily for thirty days. Grades
of abstinence which are as intense as any that can be
developed with any drug for any period of time can
be produced by the administration of 60 to 90 mg.
(1 to 1% grains) of morphine four times daily for
thirty days.

The victure of abstinence from heroin, dihydromor-
phinone hydrochloride * and metopon °° is qualitatively
similar to that of morphine, and the intensity is as

Taste 1—Simple Clinical System for Evaluating Intensity
of Abstinence Syndrome

 

 

Mild (+) Moderate (++)

Yawning Gooseflesh
Lacrimation Dilated pupils
Rhinorrhea Anorexia
Perspiration Muscle tremor

Pronounced (+++) Severe (++4+-+)
Insomnia Emesis
Restlessness Diarrhea
Hyperpnea . Weight loss
Elevation of blood pressure (5 pounds [2.3 Kg.] in 24 hours)

 

great, except in the case of metopon. Abstinence from
these drugs comes on more rapidly than does abstinence
from morphine and subsides somewhat more quickly.
Abstinence from codeine,!* while very definite, is less
intense than abstinence from morphine, comes on more
slowly and subsides more slowly. Abstinence from
meperidine hydrochloride (“demerol hydrochloride’) **
is also milder, comes on more rapidly and subsides
somewhat more rapidly than the illness from withdrawal

 

10. Andrews, H. L., and Himmelsbach, C. K.: Relation of the Intensity
of the Morphine Abstinence Syndrome to Dosage, J. Pharmacol. & Exper.
Therap. 81: 288 (July) 1944.

11. King, M. R.; Himmelsbach, C. K., and Sanders, B. S.: Dilaudid
(Dihydromorphinone): A Review of the Literature and a’Study of Its
Addictive Properties, Supplement 113 to the Public Health Reports,
United States Treasury Department, Public Health Service, 1935, p. 1.

12. Himmelsbach, C, K.; Andrews, H. L.; Felix, R. H.; Oberst, F. W.,
and Davenport, L. F.: Studies on Codeine Addiction, Supplement 158 to
the Public Health Reports, Federal Security Agency, Public Health
Service, 1940, p. i.

13. Himmelsbach, C. K.: Studies of the Addiction Liability of Demerol
(D-140), J. Pharmacol. & Exper. Therap. 75:64 (May) 1942; Further
Studies on the Addiction Liability of Demerol, ibid. 79:5 (Sept.) 1943.
11

of morphine. Abstinence from methadon ** comes on
rather slowly, is mild in intensity and subsides slowly.
Abstinence from methadon is qualitatively different
from abstinence from morphine in that few of the signs
of autonomic dysfunction, which are so prominent fol-
lowing withdrawal of morphine, are seen after with-
drawal of methadon. The comparative intensity of
abstinence following withdrawal of morphine, codeine,
meperidine hydrochloride and methadon is shown. in
figure 1.

Experience is of the utmost importance in diagnosing
and treating drug addiction. The factors which have

 

A
4

 

 

: : d dd
2 4 6 8 lio — te

Fig. 1.--Comparative intensity of abstinence from various drugs. The
solid circles indicate abstinence from morphine, the open circles abstinence
from codeine, the triangles abstinence from meperidine hydrochloride and
the squares abstinence from methadon. The vertical line of figure shows

the intensity of abstinence (clinical grades), and the horizontal row of
figures shows the number of days of abstinence.

 

 

 

operated to induce addiction must be remembered. The
problems which have arisen during the course of a
person’s becoming addicted to the drug, such as the

legal and emotional aspects and other psychiatric and -

social implications, must be developed in the addiction
history and evaluated before the individual addict can
be fully understood.

 

14. Isbell, H.; Wikler, A.; Eddy, N. B.; Wilson, J. L., and Moran,
C. F.: Tolerance and Addiction Liability of 6-Dimethylamino-4-4-
Diphenyl-Heptanone-3 (Methadon), J. A. M. A. 185: 888 (Dec. 6) 1947.

Om
12

TREATMENT OF DRUG ADDICTION

Withdrawal of drugs from narcotic addicts on an
outpatient or office basis should not be undertaken ;
it almost surely will fail. Withdrawal in any environ-
ment except that of a well managed institution under
the control of persons trained in treatment of addiction
is difficult to accomplish. In the treatment of addiction,
short hospitalization for withdrawal without a prolonged
period of institutional rehabilitation is as futile as simple
detoxification for chronic alcoholism. Men and women
addicted to the drugs controlled by the Harrison Nar-
cotic Act, as amended, are eligible for treatment as
- federal prisoners, as federal probationers or as volun-
tary patients at the Lexington and Fort Worth hospi-
tals. Applicants for voluntary treatment should write
to the Surgeon General of the United States Public
Health Service, Washington, D. C. Voluntary patients
are asked to pay $1 per day toward the cost of their
treatment, but this may be waived if the patient is
unable to pay. Women are treated only at the Lexing-
ton hospital. Since the great majority of addicts are
in an impecunious condition, the two Public Health
Service hospitals offer the only opportunity of success-
ful treatment for most addicts.

Although withdrawal is the least important part of
the treatment of drug addiction, it should be accom-
plished in the quickest, smoothest and most humane
maner possible, so as to establish good rapport between
patient and physician on which to base subsequent
’ psychotherapy and rehabilitation.

A large number of methods of withdrawing morphine
from addicted patients have been advocated over the
years past. Some of these methods of treatment have
been illogical, and some have even been more dangerous
than abrupt withdrawal of morphine.®” We are refer-
ring to the purgation, the blister, the scopolamine hydro-
bromide, atropine, insulin and heavy sedation treat-
ments.

Wieder ?® recently conducted carefully controlled
“experiments on the effect of insulin on the withdrawal
syndrome, since favorable reports on this treatment had
appeared in the literature. He observed that insulin
did not allay the withdrawal picture and, in one or two

“\. instances, seemed to make it worse.

 

“45, Wieder, H.: Objective Evaluation of Insulin Therapy of the
Morphine Abstinence Syndrome, to be published.
13

Until the discovery of methadon, rapid reduction of
the intake of morphine over a period of about ten
days has been the most satisfactory method of treatment
in our hands. In recent years, it has rarely been neces-
sary to give more than 30 mg. (% grain) of morphine
every six hours to prevent the appearance of signs of
abstinence in the first two days of withdrawal; usually
15 mg. (% grain) of morphine every six hours suffices
for this purpose. The dosage of morphine is reduced.
rapidly at the beginning of withdrawal and more slowly
near the end of the withdrawal period. It is unneces-
sary to substitute codeine for morphine. ~ ‘

Since the introduction of methadon and its accepta-
bility as a physiologic and psychologic substitute for
morphine, we have used it extensively in withdrawing
morphine from addicts by shifting to methadon which
is then withdrawn gradually. Ordinarily one can sub-
stitute one-fourth the amount.of methadon by weight.
for the dose of morphine the addict has been receiving
without signs of abstinence appearing. Since methadon
is a slowly acting cumulative drug, it is started in doses.
of 10 to 20 mg. (4% to % grain) three times daily
twenty-four hours before morphine is discontinued. The
dose of methadon is then reduced rapidly over the
course of the next ten days. Signs of abstinence still
will be observed but are not as pronounced as the
signs seen during gradual reduction of morphine
(fig. 25. Since drug addicts do not like to bear even
minimal discomfort, they may complain bitterly during
methadon reduction and may refuse to continue treat-
ment, as they often do during morphine reduction.

Adjunctive therapy to either the morphine reduction
or the substitution and reduction of methadon treat-
ments includes use of small doses of sedative drugs.
It is important not to use large doses of sedative drugs.
in treating physical dependence since excessive sedation
seems to accentuate the development of emotional upsets.
during withdrawal. Furthermore, the use of sedative
\C arti lgs prolongs emotional dependence on drug therapy.
Flow baths are helpful in relieving excessive nervous-
ness. A generous intake of fluids and an abundant.
. diet should be supplied. In cases of addiction which
~are-complicated by serious debilitating organic disease,
“the withdrawal period should be extended for as much.

“as several months. The chief complication which has

to be dealt with in the withdrawal of morphine in

  
14

current circumstances is the presence of simultaneous
barbiturate addiction. Anxiety and hysterical reactions
and attempts at malingering occur frequently during
withdrawal and must be handled by appropriate psycho-
therapeutic technics as they arise. As regards major
psychotic reactions, in a series of 400 narcotic addicts
observed, only 1 became definitely psychotic during
withdrawal.*®

 

REDUCTION OF
MORPHINE

 

 

  
 

 

SUBSTITUTION AND REDUCTION
OF METHADON

 

 

 

 

1/35 173579 13579NS
DAYS
KA><—B >< C >< D >|

Fig, 2.—Graph of treatment of physical dependence on morphine by
substitution and reduction of methadon as compared to reduction of
morphine, ane points shown represent the average intensity of abstinence
(grades 1, 2, 3 and 4 in vertical column at left) in 10 patients who were
addicted to 360 mg. (6 grains) of morphine daily. In the first experiment,
5 patients were withdrawn by simple reduction of morphine and 5 patients
were withdrawn by substitution of methadon for morphine, followed by
reduction of methadon. After fourteen days of total abstinence all 10
subjects were readdicted to morphine and, when withdrawal was again
carried out, the 5 men who were originally withdrawn by reduction of
morphine were withdrawn by substitution and reduction of methadon,
and vice versa. Period A: preliminary thirty-six hour withdrawal of
morphine for proof and assessment of intensity of physical dependence.
Period B: restabilization on morphine. In the methadon graph, substitu-
tion of 90 mg. (1% grains) of methadon for 360 mg. (6 grains) of
morphine was effected on the sixth and seventh days. Period C: reduc- ©
tion of morphine or methadon. Period D: total abstinence from drugs.

 

Prefrontal lobotomy may be useful in the treatment
of narcotic addiction so far as it relieves intractable
pain.

 

16. Pfeffer, A. Z.: Psychosis During Withdrawal of Morphine, Arch.
Neurol. & Psychiat. 58: 221 (Aug.) 1947.
15

The patient should remain in an institution for a
minimum period of four to six months, so that there
will be sufficient time to relieve the patient of any
physical ailments and give him an opportunity to
develop habits of living, eating, playing and working
without drugs. During this period, every effort should
be made to help him discover the- source of his emo-
tional difficulty and develop some insight into his
problems.

Unfortunately, only about 25 per cent of our patients
are able to benefit by other than coercive treatment.
The remainder are persons whose characters have been
so disordered from childhood that they have never been
able to grow up and make mature adjustments or
establish the proper relationship with other persons.
Voluntary patients frequently leave the hospital prema-
turely and against medical advice, so that, in the present
state of our knowledge, we are not able to do much

for these persons.

PROPER USE OF NARCOTIC DRUGS

Analgesic Effect——Since the presence of severe pain
which cannot be relieved by simpler means is the major
indication for the administration of any of the potent
analgesic drugs, an understanding of the mechanism of
relief of pain with these drugs is important in their
use. Wolff and his collaborators ‘7 have developed a
theory of analgesia which states that the pain-relieving
effects of the opiates, or similar drugs, are due to
a combination of three factors: (1) elevation of the
threshold for perception of pain, (2) an alteration of
the emotional reaction to pain and (3) the production
of sedation and sleep. Elevation of the pain threshold
and the production of sedation and sleep appear to be
less important than alteration of the emotional reaction
to pain. If morphine is given after the experimental
production of pain in human subjects, the pain threshold
is not elevated and yet the pain is relieved.‘ Since
most patients who receive morphine have experienced
pain prior to administration of the drug, elevation of
the pain threshold is probably of minor importance in
clinical practice. Relief of pain is not necessarily asso-
ciated with the production of sedation and sleep. The

 

17. Wolff, H. G.; Hardy, J. D., and Goodell, H.: Studies on Pain:
Measurement of the Effect of Morphine, Codeine and Other Opiates on
the Pain Threshold and an Analysis of Their Relation to the Pain Expe-
rience, J. Clin. Investigation 19: 659 (July) 1940.
16

barbiturates, though powerful sedative and hypnotic
drugs, are not effective analgesics. Most of the pain-
relieving action of the powerful analgesics must, there-
fore, be ascribed to a rather-specific alteration in the
emotional reaction to pain. A person with severe pain
who receives a dose of morphine, or some other potent
analgesic drug, tnay continue to perceive the pain, but,
since the pain seems to have lost its dangerous quality,
the patient disregards it and, under the hypnotic influ-
ence of the drug, drifts off to sleep. It seems reasonable
to assume that the alteration of the emotional reaction
to pain by the analgesic drugs may be associated with
the euphoria produced by these compounds. The exact

TABLE 2.—Comparative Efficacy of Single Doses of New
Drugs in Altering Various Factors Concerned
in Analgesia *

 

 

Duration of
Alteration Clinical
Elevation of Relief
Dose of Pain Reaction of Pain-
Drug (Mg.) Threshold to Pain Sedation Hours
Morphine.............0.. 10 2 2 1 4
Metopon.............00ee 6 1 1 3 4
Meperidine hydrochloride 100 4 3 2 3
Methadon................ 5-10 3 4 4 4-10
Codeine..............008e 30 5 5 5 4

 

* The figure 1 indicates the most effective of the 4 drugs in producing
the effeet noted; the figure 4 indicates the least effective of the 4 drugs.

sites and mechanism of action of these drugs within the
central nervous system are not yet understood, but
the fact that patients who have had prefrontal lobotomy
for the relief of pain continue to perceive pain, but
are not disturbed by it, suggests that the important
effect of altering the reaction to. pain may be mediated
through an action on the cortex of the frontal lobe.

The comparative efficacy of the three new analgesics,
metopon, meperidine hydrochloride and methadon and
of morphine in altering the factors concerned in anal-
gesia is shown in table 2.

With the exception of the elevation of the pain
threshold, which has been measured, the comparisons
represent the personal opinions of the authors, and were
assigned on the basis of experience with all the drugs.

Morphine.—Morphine is the most familiar drug used
for the relief of severe grades of pain. The conditions
17

which produce pain of such intensity as to require
morphine cover the entire field of medical practice, are
well known to physicians and need not be recapitulated
here. It is more important to remember that the
physician must be careful in using morphine, or any
equivalent drug, in situations in which the patient’s
complaints are out of proportion with the cause of the
pain. Such patients usually require reassurance and
emotional support rather than drug therapy. Morphine
is contraindicated in acute abdominal pain until a defi-
nite diagnosis has been established and specific treat~-
ment begun. It should not be used in the treatment
of head injuries or in any condition associated with
increased intracranial pressure. Morphine is also used
to relieve severe dyspnea due to cardiac disease or
pulmonary disease, but the drug is almost always con-
traindicated in bronchial asthma. Morphine remains the
best drug for allaying fear prior to operative procedures.
Morphine should never be used primarily for its seda-
tive action, since less dangerous drugs are available for
this purpose.

The chief disadvantages of morphine are the produc-
tion of vomiting, the depression of respiration, the
induction of spasm of. smooth muscle and the rapid
development of addiction under conditions of chronic
use. Despite these disadvantages, morphine, because of
its cheapness, reliability and rapidity of action, remains
the drug of choice for conditions requiring relief of
severe pain for periods of less than two weeks. If
vain relief is required over a longer period, metopon
and methadon are more suitable drugs.

Codeine.—Codeine is used for grades of pain which
cannot be relieved by: antipyretic drugs, but which are
not severe enough to require morphine or an equivalent
drug. As with morphine, care should be taken not to
use codeine for patients who are overreacting emotion-
ally to minor pathologic disturbances. The administra-
tion of codeine should be stopped when the need for it
has passed, since it possesses definite, though low grade,
addiction liability. The second indication for the
administration of codeine is the presence of severe
cough, but the use of the drug for this purpose should
be carefully limited.1® Coughing serves a useful purpose

 

18. Hatcher, R. A.: Narcotics in the Treatment of Coughing, J. A.
M. A. 96: 1383 (April 25) 1931.
“>

18

and should be interfered with only when the cough is
so distressing and so constant that the patient is dis-
turbed and weakened. It should be prescribed only
after other measures have failed. One should remem-
ber that, in conditions in which cough is due to irritation
of the mucous membranes of the pharynx or larger air
passages, inhalations of medical steam and the use of
lozenges or syrups containing volatile oils with local
anesthetic properties are more effective than the use
of codeine.

Metopon.—Metopon is as effective by mouth as when
administered hypodermically. Tolerance develops more
slowly to metopon '* than to morphine, and, when given
orally, metopon produces less sedation and less mental
confusion and is not as nauseating as morphine.”? After
tolerance is developed to metopon, the full analgesic
potency of the drug is restored by a short period of
withdrawal.?? Metopon is regarded as an excellent
drug for oral use in the relief of chronic pain. It is
difficult to manufacture; it is rather expensive, and
the amount available probably will always be limited.
Its total addiction lability probably equals that of
morphine.

Meperidine Hydrochloride -——Meperidine hydrochlo-
ride is a synthetic piperidine derivative which has been
widely used in medical practice since 1941. It is not
as effective an analgesic as are morphine, metopon and
methadon, but has the advantage of possessing a spas-
molytic action on the smooth muscle of the intestine of
human beings ** and the ureter.*? However, the drug
has recently been shown to increase intrabiliary pres-
sure.”*> The drug is less likely to produce nausea and
vomiting than is morphine and is said to produce less
respiratory depression. It is particularly useful in the

 

19. Eddy, N. B.: Metopon, J. Am. Pharm. A. (Scient. Edition) 8s
430 (Sept.) 1947.

20. Lee, L. E.: Studies on Morphine, Codeine and Their Derivatives:
XVL. Clinical Studies of Morphine, Methyldihydromorphinone (Metopon)
and Dihydrodesoxymorphinone-D (Desomorphine), J. Pharmacol. & Exper.
Therap. 75: 161 (June) 1942.

21. Batterman, R. C.: Clinical Effectiveness and Safety’ of a New
Synthetic Analgesic Drug, Demerol, Arch. Int. Med. 71: 345 (May)
1943, Yonkman, F. F.; Noth, P. H., and Hecht, H. H.: Demerol, a
New Synthetic, Analgesic, Spasmolytic and Sedative Agent: II. Clinical
Observations, Ann. Int. Med. 21:17 (July) 1944.

22. Climenkc, D. R., and Berg, H.: The Influence of Demerol on the
Ureter, J. Urol. 49: 255 (Feb.) 1943.

23. Gaensler, E. A.; McGowan, J. M., and Henderson, F. F.: A Com-
parative Study of the Action of Demerol and Opium Alkaloids in Relation
to Biliary Spasm, Surgery 23: 211 (Feb.) 1948.
19

relief of pain associated with spasm of smooth muscle
(except in biliary colic) and can be used in persons
who are intolerant to morphine. The addiction lia-
bility of meperidine hydrochloride is rather high—
reports in the lay press notwithstanding. Many cases
of both “primary” arid “secondary” addiction to this
drug have been seen.”4

Methadon——Methadon is a_ synthetic heptanone
derivative which is very morphine-like in its pharma-
cologic actions. In human beings it has most of the
disadvantages of morphine. It produces constitpation,
nausea, vomiting, itching of the skin and respiratory
depression.‘* It is not well tolerated by mouth and
causes more local reaction than morphine when injected
subcutaneously. Methadon is a slowly acting cumula-
tive drug and may not, in a single dose, provide adequate
pain relief. Due to its slowness of action and to the
low degree of sedation obtained with single doses, it
is not suitable for preoperative medication or for con-
ditions requiring rapid pain relief. In repeated dosage,
methadon has a powerful cumulative sedative action,
so that patients who are receiving the drug at short
intervals must be carefully observed for evidence of
excessive drowsiness.’ It is, however, an excellent drug™
for the relief of chronic pain, because ‘tolerance develops
_o its analgesic actions more slowly than does tolerance
to the analgesic action of morphine and the degree of
physical dependence on methadon ‘is less than that of
__ physical dependence on morphine.

he total addiction liability of methadon is almost
equal to that of morphine, although its physical
dependence liability is less*4 The euphoric effect of
methadon in the addict (and undoubtedly in the addic-
tion-prone person) is equal to that of morphine, so
that its habituation liability is high. The comparative
addiction liabilities of the commonly used analgesic
drugs are shown in table 3.

PREVENTION OF ABUSE OF NARCOTIC DRUGS

‘ In general, there are two approaches to the preven-
tion of drug addiction. The first line of effort is the
long range program envisaged under the National

 

24. Wieder, H.: Addiction to Meperidine Hydrochloride (Demerol
Hydrochloride): Report of Three Cases, J. A. M. A. 132: 1066 (Dec.
28) 1946. Anslinger, H. J.: Demerol, Correspondence, ibid. 132:
43 (Sept. 7) 1946. :
20

Mental Health Act. The basic problem in preventing
drug addiction is, of course, the development of a
people so emotionally sound and well integrated that
they will have no need for chemical aids to adaptive
behavior. Such proper personality integrations, which
can be achieved only through well adjusted parents,
normal environment and proper schooling in social
behavior, would do much to prevent drug addiction.
The high incidence of emotional instability in our times,
as reflected by the large numbers of noncombat psychia-
tric casualties during the war and the increasing use
of alcohol, indicates that we have a long way to go
in helping persons to adjust to life in our increasingly
complex society.

TABLE 3.—Comparative Addiction Liability of
Analgesic Drugs *

 

 

Physical Habitua-
Dependence tion

Drug Liability Liability Total
Morphine. «0... ccc eens 4 4 8
Dibydromorphinone hydrochloride... 4 4 8
Metopon..... ccc eeee este eee eeteceeeeetes 3 4 q
Meperidine hydrochloride............... 2 3 5
Methadon........ ccc c cece cece ee ete eences 1 4 5
COdEINE.. 0... e cee ccc eee ete ee anes 2 1 3

 

* Comparative addiction liability of analgesic drugs. The numeral 4
indicates that the particular drug has the greatest liability of all the
drugs with respect to the particular addiction characteristic shown; the
numeral 1 indicates the lowest liability: the sum of the two character-
istics gives the total addition liability, the highest possible addiction
liability score beng 8 and the lowest 0.

The second approach to the prevention of drug addic-
tion, and the point of immediate attack, is to separate
effectively the addiction-prone person, or the ex-addict,
from narcotic drugs. The Harrison Narcotic Act, with
its legal prohibitions and penalties, its vigilance in pre-
venting the introduction of contraband narcotics into
the market and its careful control over use of narcotics,
has had a progressive influence on the reduction and
prevention of narcotic addiction. In addition to the
Harrison Narcotic Act, the Geneva Convention of the
League of Nations has operated to reduce worldwide
production and refining of opium.

Although accidental addiction by medical use occurs
occasionally, the great majority of patients become

_ addicted under the influence of other addicts, and the

efforts of the Public Health Service hospitals for the
21

treatment of narcotic addicts at Fort Worth, Tex., and

Lexington, Ky., prevent addiction so far as they cure

persons who would otherwise become foci of “infec-

tion.” The hospital at Lexington alone has treated

slightly more than 11,000 patients since 1935. Fol-

low-up reports indicate that over 16 per cent of these ~
patients have remained abstinent over a seven year

period, and probably at least an additional 20 per cent
have remained abstinent for extended periods of time.

Physicians should keep the danger of addiction to

analgesic drugs in mind and should exercise caution

in prescribing them. These drugs should never be used

when other drugs or other measures will suffice. The

dosage should be held to the minimum compatible with

adequate pain relief, and the interval between doses -
should be as great as possible. The drugs should b Tom
discontinued as soon as the need for pain relief ha&/
passed. They should never be used primarily for their
sedative actions. In chronic cases, they should be
administered orally whenever possible.. Self medication ~
with a hypodermic should not be allowed. The drugs

should not be given intravenously unless the need for

rapid pain relief is great, since this method produces

maximum euphoria and carries an increased risk of

addiction. The drugs should not be administered to
persons with known neurotic personalities unless defi-

nite indications for the use of a potent analgesic are

present. Narcotic. drugs should never be used for the

relief of symptoms due to alcoholic excess, since alco-
holic persons are very addiction-prone. Analgesic drugs

should rarely, or never, be used in the treatment of

asthma, since asthmatic persons are very susceptible to

addiction. It is significant that in many cases of mor-

phine addiction and several of the cases of primary

addiction to meperidine hydrochloride observed at

Lexington addiction resulted from its use for the relief

of asthma.

Suggestions are made from time to time that clinics
should be established where known addicts would be
given drugs free, or sold drugs at minimum cost, for
“the continued support of their addiction. The pro-
ponents of this plan believe that addiction is incurable
or that treatment is inhumane and that if addicts are
given the minimum amounts of drugs necessary to

ste
22

maintain their addiction lawlessness attendant on con-
traband traffic in narcotic drugs would be eliminated.
This reasoning is unrealistic, as has been shown by
several attempts in this country and abroad that have
failed. Addicts on such “rations” connive to get more
than their allotted amount of drugs, so that they can
increase their dosage and continue to obtain a euphoric
effect. They may sell, or give away, part of the extra
supply so obtained to persons who are not addicted.
This creates new addicts who are potential customers
for the contraband market and thus increases the prob-
lem which the ration plan is supposed to abolish. Fur-
thermore, many addicts can be treated and learn to live
a useful effective life instead of one of personal neglect,
indolence and semisomnolence which is so typical of
the addict. Addiction is ‘infectious,’ and treatment,
rather than support of addiction, is necessary to mini-

mize its spread.
SUMMARY

Because of vigorous enforcement of the Harrison
- Narcotic Act and to treatment of addicts in federal
facilities the total number of narcotic drug addicts in
the United States has declined from 150,000 to 200,000
in 1914 to approximately 48,000 at the present time.

- Drug addiction is a state in which a person has lost
the power of self control with reference to a drug and
abuses the use of the drug to such an extent that the
person or society is harmed. The drugs to which
addiction commonly occurs in the United States are
opium and the opium alkaloids, the synthetic morphine-
like analgesics, the barbiturates, bromides, alcohol,
marihuana, cocaine, amphetamine and, rarely, peyote.
The characteristics of addiction to these drugs are dis-
cussed.

Drug addiction is primarily a psychiatric problem
and should be regarded as a symptom of a basic under-
lying personality maladjustment. The common person-
ality types of drug addicts are described. The diagnosis
of narcotic addiction is usually easy, but may be diffi-
cult. Isolation of the patient and observation for signs
of abstinence is, at times, the only conclusive means
of diagnosis.

Withdrawal of drugs is the first and the least impor-
tant step in the treatment of narcotic addiction. With-
drawal of morphine is best achieved by a ten day
23

reduction of morphine or by substitution and reduction
of methadon. Institutional therapy is necessary for the
successful treatment of addiction. A minimum period
of treatment of four to six months is essential. The
patient’s entire personality must be reoriented by appro-
priate psychotherapeutic technics.

The pharmacologic characteristics, the advantages and
disadvantages, and the comparative addiction liabilities
of the older and newer analgesic drugs are discussed.
The prevention of drug addiction involves the develop-
ment of an emotionally sound people through the pro-
gram of the National Mental Health Act, the reduction
of the illegitimate use of narcotics by the control mea-
sures provided for under the Harrison Narcotic Act,
the isolation and treatment of addicts, which prevents
them from spreading addiction, and proper cautious use
of addicting drugs by physicians.

+

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