ON THE NATURE OF ADDICTION AND

HABITUATION*
By ABRAHAM WIKLER, M.D.
Chief of the N.I.M.H. Addiction Research Centre, Lexington,
Ky., U S A .

The fact that a Society for the Study of Addiction has been in
existence for 75 years, in a country where the problem has always
been relatively small, attests at once to the scientific curiosity of
the British medical profession and to the intriguing nature of the
subject of its interest. Moreover, the vitality of the Society after so
long a period of study, indicates that the problem is not yet com-
pletely understood in spite of decades of intensive research. In
particular, not only your Society and our Addiction Research
Centre, but physicians, lawmakers and the general public every-
where are concerned above all with one aspect of the problem.
namely, the persistent tendency to repeated relapse after successful
withdrawal of the drug in question. This gap in our knowledge,
of which we are constantly reminded by the often discouraging
results of attempts to achieve permanent cures, is characteristic of
our information about the abuse, not only of drugs of the morphine-
type, but also of the two other major drugs of “addiction”---
barbiturates and alcohol. I am sure instances can be cited of
inveterate relapse to abuse of a number of other drugs, such as
those of the amphetamine class, cocaine and marihuana, but it
would seem that these constitute a less important problem since,
except sporadically (as in the case of abuse of amphetamine dur-
ing the immediate post-war years in Japan), they do not receive as
much publicity as opiates, alcohol and barbiturates, and to my
knowledge it has not been found necessary to establish permanent,
specialized institutions for the treatment of such patients.
This curious difference may well serve as a point of departure
for some speculations on the nature of addiction and habituation,
which I shall now present for your consideration. In clinical prac-
tice, the immediate therapeutic problem is withdrawal of the drug
* Read before the Society on the 18th October, 1960, in the Rooms of
the Medical Society of London, the President, Prof. A. D. Macdonald, being
in the chair.
73
74 THE BRITISH JOURNAL OF ADDICTION

of “addiction”. This is accomplished rather easily in the cases of

patients using amphetamine, cocaine or marihuana, such diffi-
culties as are encountered being due to the toxic psychoses which
often bring the patients to the hospital, and not to the consequences
of withdrawal of the drug. In contrast, withdrawal of drugs of the
morphine-type, barbiturates or alcohol is attended by the risk of
unleashing a train of highly drug-specific abstinence phenomena,
the control of which may tax the resources of the medical and
psychiatric staff, as well as those of the patient. The relatively
invariant features of such abstinence phenomena may be desig-
nated as “non-purposive” in the sense that objects or persons in
the external environment are not essential for their occurrence.
Thus, after long-continued use of these drugs, severe autonomic
disturbances are likely to occur after abrupt withdrawal of agents
of the morphine type, and convulsions and/or delirium after abrupt
withdrawal of barbiturates or alcohol. More variable, but coupled
very often with such “non-purposive” abstinence phenomena, are
behavioral changes that may be termed “purposive” in the sense
that objects or persons in the external environment, indentifiably
involved in acquisition of the drug, are essential for their mani-
festation. Thus “craving” for morphine-type drugs, barbiturates or
alcohol, together with appropriate manipulatory activities notori-
ously increase the difficulties of withdrawing these agents.
This state of affairs is the criterion used empirically in the
diagnosis of “addiction”, or, perhaps more descriptively, “pharma-
cogenic dependence”, to take cognizance of the essential opera-
tions involved in demonstrating its existence-namely, abrupt
withdrawal of the drug of abuse and observation of drug-specific
abstinence phenomena, both “physical” (non-purposive) and
“psychic” (purposive); though to be sure, emphasis is usually placed
on the former because they are more readily measured. In accord-
ance with this terminology, the results of our clinical experience
indicate that, on the whole, drugs like amphetamine, cocaine or
marihuana are less “addicting” than drugs of the morphine-type,
barbiturates or alcohol, both “physically” and “psychically”.
Some possible reasons for such a close (though not invariable)
relationship between the “physical” and the “psychic” aspects of
addiction to drugs of the morphine-type, as well as for the high
rate of relapse after “cure” (or “habituation”) in cases of this sort,
were suggested many years ago by certain features of the histories
given by narcotic (i.e., opiate) addicts, and observations made in
the course of psychodynamic study of a patient during experi-
 THE BRITISH JOURNAL OF ADDICTION 75
mental self-regulated readdiction to morphine (1). It is not surpris-
ing, of course, that “post-addicts’’ (patients with previous histories
of narcotic addiction) report an unusual sense of well-being
after injection of a drug with morphine-like properties, which in
the absence of any valid objective justification for such a report
(e.g., relief of pain) is commonly designated as “euphoria”. Con-
sistently, however, such subjects report that with successive doses
repeated several times daily, the “euphoric” effects decline pro-
gressively, and although such “tolerance” can be overcome to a
considerable extent by progressively increasing the dose, the
intensity of the initial “euphoria” is not regained as long as the
uninterrupted schedule of drug administration is maintained. Why,
then, do “addicts” typically continue to take the drug in the face
of such presumed disillusionment? The usual answer to this
question is that they fear the distress of acute abstinence. Yet,
after years of experience, most “addicts” have learned that narcotic
drug withdrawal can be accomplished quite comfortably by
gradual reduction of the dose, or substitution and subsequent with-
drawal of methadone. Furthermore, under experimental conditions,
narcotic “addicts” are quite willing to undergo abrupt withdrawal
even though they do indeed suffer considerably (sometimes
severely) when this is done, in return for relatively paltry
incentives, such as the prospect of reduction of a long prison
sentence by a few days or weeks.
A perhaps more plausible explanation is one that may be inferred
from a remark made by the subject of the study cited above (1).
After having acquired a high degree tolerance to morphine by
repeated self-injections, he commented that although he could not
regain the initial “euphoric” effects, the drug produced another
sort of pleasure, namely that arising from the relief of such
abstinence discomfort as developed toward the end of the intervals
between injections. In explanation, he drew an analogy from com-
mon experience, remarking that while a steak always tastes good,
it tastes even better when one is hungry. In other words, with the
development of “pharmacogenic dependence”, a continuous cycle
of drug-induced “need” and “gratification” develops, which can
motivate behaviour in much the same way as the recurrent cycles
of hunger. thirst or other “primary needs” and gratifications there-
of, in normal life. Expressed in the language of instrumental con-
ditioning theory, each dose of the drug serves to reinforce
drug-seeking behaviour through reduction of the drive (early
abstinence changes) produced by the previous dose. Furthermore
76 THE BRITISH JOURNAL OF ADDICTION

the preoccupation of narcotic “addicts” with “hustling” for the

drug (i.e., drug-seeking behaviour in an extra-legal sense) not only
in actuality when actively “addicted” but also in verbalized
phantasy during non-addicted interludes (especially in the presence
of other “addicts” or “post-addicts”), suggests that drug-seeking
behaviour, initially reinforced in the manner described, may be-
come conditioned to “secondary reinforcers” or stimuli (e.g.. “bad
associates”) regularly associated with acquisition of the drug dur-
ing addiction. Complementing this formulation, it may also be
postulated theoretically that during addiction the cyclic organismal
changes produced by the drug, initial abstinence-reducing and
subsequent abstinence-generating effects, also become conditioned
to “secondary reinforcers” in the manner of classical conditioning
theory(2). That this may actually be the case is suggested by state-
ments cccasionally made by “post-addicts’’ to the effect that
withdrawal phenomena, such as lacrimation, rhinorrhea, yawning
and intense “craving”, may recur long after drug-withdrawal when
they find themselves in situations in which narcotic drugs are
readily available.
On the basis of these considerations, relapse (or “habituation”)
can be viewed as a result of conditioning processes, operating in
somewhat different manners, depending on whether the reversion
to drug use occurs “early” or “late” after withdrawal of the addict-
ing agent. As long as some residue of “unconditioned” pharma-
cogenic dependence persists (possibly up to six months following
withdrawal of morphine in man), relapse may be due simply to
incomplete extinction of reinforced drug-seeking behaviour. Later,
relapse may be initiated by recurrence of at least some fragments
of the abstinence syndrome as a conditioned response, coupled
with traces of previously reinforced drug-seeking behaviour that
remained as a result of non-extinction during previous episodes
of addiction and “cure”.
Admittedly, these views are highly speculative, but some experi-
mental evidence can be adduced in their support. Central to the
argument is the assumption that repeated doses of morphine-like
drugs do produce organismal changes, independent of, though
presumably subjected to conditioning factors, that are responsible
for the abstinence syndrome. About this there can be but little
question, since it has been possible to demonstrate that chronic
decorticated and chronic spinal dogs do develop tolerance to, and
exhibit abstinence phenomena after repeated administration of
morphine or methadone, and analogous observations have also
 . DYNAMICS OF DRUG ABUSE
(INSTRUMENTAL CONDITIONING PARADIGM)

1 I1 I11
Phases Episodic intoxication Pharmacogenic dependence Relapse after cure (“Habituation”)
(“Euphoria”) (“Addiction”)
Early Late
More frequently: Medical and “Bad Associates”
Discriminative “Bad associates” “Bad associates” Law-enforcement Sensorial effects
Stimuli Less frequently: contingencies of drugs
Medical contingencies
Reinforcement Extinction by
Processes Occasional Continuous or aperiodic “satiation” (not Variable
Schedules non-reinforce-
ment)
~ ~

Sources Anxieties (homeostatic, Mainly homeostatic and Same as in IT but

Primary sexual) sexual anxieties induced decreasing
Curiosity by cellular “counter- after peak Conditioned
Boredom adaptations” to repeated sources of
Anhedonia doses of “addicting” drugs reinforcement,
generated mainly
Secondary “Anomie” Status in “addict-society” Hostility in phases
I Hostility 1 Guilt 11 and 111
(Early)
Auxiliary 1 “Effort” factor i “Effort” factor (intensified) Generalization
of anxiety
Progressive increase in Conditioned
Behavioral “Experimenting” with drugs dosage (“tolerance”) Abstinence abstinence
phenomena “Hustling” for drugs syndrome phenomena
(fragmentary)
Objectively unwarranted Relief of As in I plus
Drug effects “sense of unusual well-being” Gratification of “craving” Abstinence “drive”
“Indifference” Distress (Conditioned
w “Elation” “Hustling” ?)
78 THE BRITISH JOURNAL OF ADDICTION

been made in a “spinal” man(3,4,5). Some highly suggestive data

have also been reported by other investigators, bearing on the
question of conditioning, both of the classical(6) and instrumental
varieties(7,8). We have been pursuing these problems for several
years in our own laboratories, but as yet only some “pilot” studies
have been completed(9). Using a very dilute aqueous solution of a
benzimidazole derivative with potent morphine-like properties as
a reinforcing agent taken orally, our evidence suggests that with
provision of external discriminating cues, rats can acquire a
preference for the drug (in choice trials in which drug solution
and tap water are offered) as a result of training with an instru-
mental conditioning procedure, and that probably such preference
is based on the pharmacological effects of the drug. In these ex-
periments, however, not only morphine-addicted but also saline-
control rats acquired such preference, which persisted in both
groups of animals for at least 34 days following termination of
injections (of morphine or saline respectively). At present the data
are of interest mainly from the standpoint of technique, since oral
reinforcement by a drug with morphine-like properties permits
investigators to circumvent the aversive conditioning that is likely
to occur when injections are used.
While the burden of this communication has been concerned
chiefly with pharmacogenic factors, sight should not be lost of
many other important variables that contribute to the genesis of
relapse, such as those relating to personality and anxiety-generating
environmental situations. In our present state of knowledge, the
precise manner in which these operate cannot be stated with
certainty, but one possible view is that, at least to some extent,
they too operate in accordance with instrumental conditioning
theory. To complete the picture, so to speak, I have therefore
appended a table in which an attempt is made to formulate the
sequence of events in the history of a typical narcotic “addict”,
from “euphoria” to “addiction” to “habituation” as a function
of the interaction of many variables according to the paradigm of
instrumental conditioning, more as a guide-line for future research
than as a final statement of the nature of addiction and habituation.

REFERENCES
(1) Wikler, A., A Psychodynamic Study of a Patient During Self-
Regulated Readdiction to Morphine, Psychid. Quart. (1952),
26, 270-293.
 THE BRITISH JOURNAL OF ADDICTION 79
(2) Wikler, A., Recent Progress in Research on the Neurophysiological
Basis of Morphine Addiction, A m . J. Psychiat. (1948), 105,
329-338.
(3) Wikler, A., and Frank, K., Hindlimb Reflexes of Chronic SpinaI
Dogs During Addiction to Morphine and Methadone, J .
Pharmacol. & Exper. Therup. (1948), 49, 382-400.
(4) Wikler, A., Reactions of Dogs without Neocortex during Cycles
of Addiction to Morphine and Methadone, Arch. Neurol. &
Psychiat. (Chicago) (1952), 67, 672-684.
( 5 ) Wikler, A., and Rayport, M., Lower Limb Reflexes of a “Chronic
Spinal” Man in cycles of Morphine and Methadone Addiction,
Arch. Neurol. & Psychiat. (Chicago), (1954), 71, 160-170.
(6) Irwin, S., and Seevers, M. H., Altered Responses to Drugs in the
Post-Addict (Macca Mulatta), J . Pharmacol. & Exper. Therap.
(1956), 116, 31-32.
(7) Nichols, J. R., Headlee, C. P., and Coppock, H. W., Drug Addic-
tion. I. Addiction by Escape Training, J. A m . Pharmaceutical
A . (1956), 45, 788-791.
(8) Beach, H. D.. Morphine Addiction in Rats, Canad. J. Psychol.
(1957), 11, 104-112.
(9) Wikler, A., Green, P. C., Smith, H. D., and Pescor, F. T., Use
of a Dilute Aqueous Solution (5 mcg/ml) of a Benzimidazole
Derivative with Potent Morphine-like Actions Orally as a
Presumptive Reinforcing Agent in Conditioning of Drug-Seek-
ing Behaviour in Rats, Federation Proc., 19,(l), 22 (Mar. 1960.)