Drugs

I. PsychopharmacologySherman Ross

BIBLIOGRAPHY

II. Drug Addiction: Organic and Psychological AspectsAbraham Wikler

BIBLIOGRAPHY

III. Drug Addiction: Social AspectsJohn A. Clausen

BIBLIOGRAPHY

I PSYCHOPHARMACOLOGY

Although psychopharmacology is a relatively new scientific word, the interactive effects of drugs and behavior are perhaps as old as man himself. This presentation will describe contemporary interest in psychopharmacology and will emphasize the social research frontiers. It will not attempt to describe the emerging body of human and animal research results or the treatment aspects of drugs.

Although there are clearly a number of focuses for discussion, the individual human has been selected as the center of analysis; this article will deal with a number of individual and social factors relating to the effects of drugs. These factors are complex and generally poorly identified and weakly conceptualized. The ramifications of the questions lead one to consideration of the pathways of activity in the nervous system, the complexities of biochemical analysis, the assessment of human performance in laboratory or simulated situations, the management of patients, and the social matrix in which all of human behavior is embedded.

Historical considerations. Drug utilization for health, religious, or individual purposes is one of the many primary characteristics of human behavior in a wide variety of cultures. Drugs thus constitute an almost universally present element in human social behavior, and one to which individual reinforcement, social training, and private meaning are attached. One of the world’s oldest professionals, the medicine man, has long made use of a variety of chemical substances in the technology of his affairs.

Although the term “psychopharmacology” has been used with increasing frequency over the past few years, the concept is by no means new to psychology. Studies of the effects of drugs on the behavior of animals were undertaken in the nineteenth century, and the classic investigations of the effects of caffeine on human behavior were carried out by Hollingworth (1912) in the first decade of the twentieth century. This series of studies embodied many of the aspects of good design and may still have value as a model for analysis of the effects of drugs on human behavior.

The current dramatic expansion of interest in psychopharmacology as a special area dates from the early 1950s. In its early phases it was a product of the joint action of pharmacologist and psychiatrist in their attempts at modification of the behavior of psychiatric patients.

Since the early 1950s, when drugs such as reserpine and chlorpromazine were introduced, the list of compounds has grown, although some central questions surround these drugs and their utilization.

Problems. Any real understanding of drugs that affect behavior depends upon the development of adequate theory relating biochemical or pharmacological events to behavioral events. Callaway and Stone (1960) have examined the nature of theory in this area and find that an integrating theory is still to be developed. On the biochemical side they find that the problem is formidable and aggravated by the lack of appropriate behavioral referents. Theories proposed by behavioral scientists may greatly oversimplify the underlying biological complexities. On the other hand, theories constructed by biochemists and pharmacologists may be naive about the behavioral complexities. No available theory is consistent with the available data, and many approaches use ambiguous and subjective terms. Callaway and Stone express the hope that the new psychotropic drugs can serve as a valuable class of independent variables in an integrated theory of behavior.

The task of analyzing the specific pharmacological effects of a drug is confounded by the history, learned expectations, and social roles of the individuals involved. Poffenberger (1942, pp. 200–202) discussed several major sources of error in drug investigations. He expressed serious concern about the “suggestibility of people who have a knowledge of the effects to be expected,” the lack of control subjects, the difficulties in the selection of appropriate measures of drug effects, the short duration of drug studies, and, finally, the facts of interindividual and intraindividual differences [seeSuggestion].

Modell has recently reviewed the problem of experimental controls in clinical pharmacology. He writes:

It may surprise some laboratory workers as well as a large number of clinicians that the pharmacologic experiment in man is really far more difficult than in the animal. The training and the orientation of the physician, as well as his relationship to the patient, make him an interested and purposive observer rather than a precise and objective one. Also realistic restrictions on the techniques that may be used in making observations on man make the clinical experiment difficult to perform and limit the depths which can be proved directly. Then there is the subject, whose human mind, human culture, human society, and human frailties make it uniquely difficult to experiment on him. All of these factors make the establishment of controls in a human experiment quite a different kettle of fish from the laboratory procedure of dividing littermates into two equal groups. (1963, p. 372)

Methodological developments

Experimenter and subject bias are presumably dealt with by the double-blind control, in which both E and S are prevented from knowing who has been assigned to a specific experimental group. The placebo presumably is utilized to deal with the implications of medication, and randomization of other variables permits dealing with extraneous factors. The advantages and liabilities of the double-blind procedure have been discussed by Nash (1962) and need not be pursued here [seeExperimental design].

Placebo effects and research design

The placebo issue has also been of much interest and has been reviewed by Wolf (1959) and by Roueche (1960, pp. 85–98). Beecher (1955) has stressed the importance of the placebo concept, distinguishing between the effects of suggestion and the direct pharmacological effect. Wolf defines placebo effect as “any effect attributable to a pill, potion, or procedure, but not to its pharmacodynamic or specific properties” (1959, p. 689).

An experimental design involving an extra group of subjects in addition to the usual drug, placebo, and untreated groups has been developed (Ross

et al. 1962; Lyerly et al. 1964). This extra group, called the “drug disguised group,” receives the drug in a disguised form. Table 1 outlines this fourfold design.

The main question to which this design is directed is the analysis of drug effects. Most studies are based on a drug group—placebo group design or, less frequently, a drug group-placebo group-untreated control group design. In the typical drug—placebo experiment, both drug and placebo groups are given pills with the same instructions. The effects observed in the drug Ss are generally attributed to the pharmacological properties of the agent after subtraction of the effects found in the placebo Ss. But these “drug” effects may be partly a function of Ss’ expectations or of the experimental or therapeutic setting. When a nontreatment group is added to the design, however, the differences between the untreated and the placebo groups can be attributed to the placebo effect. The special advantage of the four-group design is that it permits direct assessment of drug and placebo effects. In a typical experiment the drugs and placebos were given to the Ss in capsules, and all Ss received orange juice, which was also the vehicle for the disguised medication. The untreated group received orange juice only.

One experiment has been reported on the effects of d-amphetamine sulfate. The results of this experiment, carried out with neutral instructions, indicated a positive pill effect on mood, that is, the S felt more “comfortable,” and a negative effect of the drug when administered in the disguised condition. The untreated group provided results similar to those of the group that received the drug as a pill. Motor performances of both the drug and the drug-disguised groups were significantly poorer than those of the placebo and untreated groups.

Effects of expectancies. A second experiment was designed to determine the specific effects of direct and conflicting instructions and the effects of two drugs (amphetamine sulfate and chloral hydrate) that might be expected to produce different pharmacological and perceptual effects. Two sets of instructions were developed to lead Ss to expect that the capsules they swallowed would yield the specific effects of one of the two drugs. Groups similar to those in the previous experiment were used.

Instructions alone affected motor performance but had little or no effect on mood. Direct instructions, appropriate to the presumed drug effects, produced performance deterioration with the simple motor tasks used. Conflicting instructions, inappropriate to the presumed drug effects, counteracted much of the drug-produced decrement. A slight decrement in performance was found in the placebo group which received instructions appropriate to the effects of amphetamine. Amphetamine produced reports of greater comfort on the “mood index” than did chloral hydrate. On the other hand, the chloral hydrate instructions resulted in greater comfort than the amphetamine instructions. There was no interaction between drug effects and instructional effects. The two placebo groups did not differ significantly on the mood index. The effects of instructions on mood were found only when the drug was present.

The general problem of placebos has been analyzed from a variety of viewpoints (Fisher 1962; Gorham & Sherman 1961; Hawkins et al. 1961; Kast 1961; Wilson & Huby 1961) and is far from settled.

Personality and social aspects

Increased sophistication has been emerging in the field of human experimentation, stimulated by analyses of the social psychology of the psychological experiment (Orne 1962; Rosenthal 1963). The issue of ecological validity and the appropriate generalization from the laboratory to nonexperi-mental situations were treated by Brunswik (1947). Perhaps it is fair to say that the problem has not received its appropriate emphasis to date. Orne has suggested that the subject must be recognized as an active participant in any experiment and that it may be fruitful to view the psychological experiment as a special form of social interaction. He has proposed that the behavior of the subject is a function of the total situation, which includes the experimental variables being studied and at least another set of variables. The latter group has to be put under the heading of “demand characteristics” of the experimental situation. Rosenthal has described a program of research dealing with experimenter bias. It is shown that the expectation of the experimenter was a partial determinant of the results of behavioral research. The issues in these studies are vital ones for psychopharmacology, and it is hoped that future research will attend to these problems.

Drug therapy

A recent analysis of psycho-pharmacology and personality takes stock of personality measurement in relation to drugs. It reports the rather meager progress in psychopathology and deduces a static plateau in personality measurement “cushioned by factor analysis on the one hand and by psychodynamics on the other” (Zubin & Katz 1964).

In the specific domain of the treatment of hospitalized psychiatric patients, additional aspects of the effects of drugs become of interest to the social scientist. Klerman (1961) states that before the 1930s major interest lay in such disorders as general paresis or epilepsy. Metrazol, electroconvulsive therapy, insulin coma, and lobotomy made their appearance at this time. It was in the decade before World War ii that schizophrenia became the center of attention. Psychotherapeutic innovation also appeared under the leadership of Harry Stack Sullivan, Jacob Moreno, Frieda Fromm-Reichmann, and others. Klerman indicates that it is unfortunate for drug evaluation that the advent of the newer tranquilizing agents in the 1950s coincided with a wave of hospital reforms and innovations in the treatment of psychotic patients. This interaction is a complex one, and it is difficult to assess the effects of “drugs” on hospital admission, readmission, and other rates.

In addition to affecting the individual patient or subject the psychotropic drugs also affect the hospital milieu and functional organization. Elkes has described this interaction as follows:

In an age of revolutions, one is apt to get used to revolutions. In considering the impact of the pharmacotherapies on the management of the psychoses in a mental hospital, one is apt to be reminded of the violent changes brought about in the past by the introduction of other somatic therapies, such as deep insulin coma, electroplexy, and the lobotomies. Each of these has wielded changes, based essentially upon relatively short-term results; only in recent years could these be viewed against the perspectives of long-term follow-up studies. The changes in management, and the attendant changes in attitude, however, have stayed and become cumulative. It is quite possible that a similar fate may befall the pharmacotherapies of mental disorder, though three important differences distinguish them from earlier treatments and encourage a more hopeful view. The first is the fact that these therapies can be graded and made individual in a way which was quite impossible with the less variable and massive procedures used in the past. Secondly, they can be used on a scale far larger than the earlier therapies. Thirdly, whereas in the past systematic studies of mode of action followed essential empirical findings and measures, the empirical findings of the pharmacotherapies are being increasingly related to a growing body of modern theoretical neuropharmacology and neurochemistry. Theories are thus likely to keep abreast of clinical findings in a way never before witnessed in psychiatry, and are likely to make these ever more precise, discriminate and long-term.

The impact of the drug therapies on mental hospital population is essentially threefold. They have altered the immediate management and treatment of certain types of acutely disturbed psychotic patients; they have mobilized large chronic populations hitherto secluded in the continued-treatment units of the average mental hospital; and, in individual cases, have made possible measures of rehabilitation which would have been very difficult to achieve in their absence. Lastly, they have increased and made more urgent the contacts between the mental hospital and the community. In terms of all these effects the drugs are wielding profound changes in staff attitudes at all professional levels. The precise pattern of these changes at present is far from clear, and for the moment can only be discussed in the broadest terms. (1961, pp. 91–92)

With respect to the clinical treatment of the chronically hospitalized patient, there has long been evidence that increases in staff attention alone will produce symptomatic improvement (Galioni et al. 1953). A recent study by Bullard, Hoffman, and Havens (1960) indicates that drugs may be more important than environment in producing changes in chronic patients. An excellent review of this problem by Hordern and Hamilton (1963) indicates its complexities and the lack of clarity regarding the contributions to patient response of drugs and special nondrug treatments and of staff and patient attitudes. It is unfortunate but true that the effects of the drug and/or environment found in any single study represent only a single case in the larger sense, since it is almost impossible at present to measure or even meaningfully hypothesize what aspects of the staff–patient–milieu–drug context are responsible for the effects produced.

The introduction to a recent volume on specific and nonspecific factors in psychopharmacology states the central issue cogently: “The concept of specificity of drug action is at the heart of all pharmacological enquiry and speculation, and the stated hope of chemotherapy. Yet, in the unfamiliar terrain now extending between biochemistry and behavior, the term is assuming new and unexpected meaning. The interaction between the somatic and the symbolic compels a revision of premises, a recalibration of tools, and a reassessment of rules” (Elkes 1963, p. v). In this revision, recalibration, and reassessment, all of the sciences of man are involved. The social sciences have their special assignment and central contribution.

Sherman Ross

[Directly related are the entriesMental disorders, article onbiological aspects, andMental dis-orders, treatment of, article onsomatic treatment. Other relevant material may be found inDrinking and alcoholism.]

BIBLIOGRAPHY

Beecher, Henry K. 1955 The Powerful Placebo. Journal of the American Medical Association 159:1602–1606.

Brunswik, Egon 1947 Systematic and Representative Design of Psychological Experiments: With Results in Physical and Social Perception. Berkeley: Univ. of California Press.

Bullard, Dexter M.; Hoffman, Barbara R.; and Havens, Leston L. 1960 The Relative Value of Tranquilizing Drugs and Social and Psychological Therapies in Chronic Schizophrenia. Psychiatric Quarterly 34:293–306.

Callaway, Enoch; and Stone, George C. 1960 Psychopharmacologic Theories: A Critical Review. Clinical Pharmacology and Therapeutics 1:247–267.

Elkes, Joel J. 1961 Psychotropic Drugs: Observations on Current Views and Future Problems. Pages 65–114 in Conference on Experimental Psychiatry, Western Psychiatric Institute and Clinic, 1959, Lectures on Experimental Psychiatry. Univ. of Pittsburgh Press.

Elkes, Joel J. 1963 Introduction. In Symposium on Specific and Non-specific Factors in Psychopharmacology, Montreal, 1961, Specific and Non-specific Factors in Psychopharmacology: Proceedings. Edited by Max Rinkel. New York: Philosophical Library.

Fisher, Seymour 1962 On the Relationship Between Expectations and Drug Response. Clinical Pharmacology and Therapeutics 3:125–126.

Galioni, E. F.; Adams, F. H.; and Tallman, F. F. 1953 Intensive Treatment of Backward Patients: A Controlled Pilot Study. American Journal of Psychiatry 109:576–583.

Goodman, Louis S.; and Gilman, Alfred Z. (1941) 1965 The Pharmacological Basis of Therapeutics. 3d ed. New York: Macmillan. → Covers literature on the effects of drugs on human behavior, from a pharmacological viewpoint.

Gorham, Donald R.; and Sherman, Lewis J. 1961 The Relation of Attitude Toward Medication to Treatment Outcomes in Chemotherapy. American Journal of Psychiatry 117:830–832.

Hawkins, David R. et al. 1961 A Multivariant Psycho-pharmacologic Study in Normals. Psychosomatic Medicine 23:1–17.

Hollingworth, H. L. 1912 The Influence of Caffeine on Mental and Motor Efficiency. Archives of Psychology No. 22.

Hordern, Anthony; and Hamilton, Max 1963 Drugs and “Moral Treatment.” British Journal of Psychiatry 109:500–509.

Kast, Eric C. 1961 Alpha-Ethyltrytamine Acetate in the Treatment of Depression: A Study of the Methodology of Drug Evaluation. Journal of Neuropsychiatry 2 (Supplement) no. 1:114–118.

Klerman, Gerald L. 1961 Historical Baselines for the Evaluation of Maintenance Drug Therapy of Discharged Psychiatric Patients. Pages 287–301 in Milton Greenblatt, David T. Levinson, and Gerald L. Klerman (editors), Mental Patients in Transition. Springfield, III.: Thomas.

Krantz, John C. Jr.; and Carr, C. Jelleff (1949) 1965 The Pharmacologic Principles of Medical Practice. 6th ed. Baltimore: Williams & Wilkins. → Contains a major section on psychopharmacology: “The Use of Drugs in the Treatment of the Mentally III.”

Lyerly, Samuel B. et al. 1964 Drugs and Placebos: The Effects of Instructions Upon Performance and Mood Under Amphetamine Sulfate and Chloral Hydrate. Journal of Abnormal and Social Psychology 68: 321–327.

Modell, Walter 1963 The Protean Control of Clinical Pharmacology. Clinical Pharmacology and Therapeutics 3:371–380.

Nash, Harvey 1962 The Double-blind Procedure: Rationale and Empirical Evaluation. Journal of Nervous and Mental Disease 134:34–47.

Orne, Martin T. 1962 On the Social Psychology of the Psychological Experiment: With Particular Reference to Demand Characteristics and Their Implications. American Psychologist 17:776–783.

Poffenberger, Albert T. 1942 Principles of Applied Psychology. New York: Appleton.

Rosenthal, Robert 1963 On the Social Psychology of the Psychological Experiment: The Experimenter’s Hypothesis as Unintended Determinant of Experimental Results. American Scientist 51:268–283.

Ross, Sherman; and Cole, Jonathan O. 1960 Psycho-pharmacology. Annual Review of Psychology 11:415–438. → An analysis of the major literature.

Ross, Sherman et al. 1962 Drugs and Placebos: A Model Design. Psychological Reports 10:383–392.

RouechÉ, Berton 1960 Placebo. New Yorker October 15:85–86, 88, 90–92, 97–98, 100, 102–103.

Uhr, Leonard; and Miller, James G. (editors) 1960 Drugs and Behavior. New York: Wiley. → A general reference book.

Wilson, Cedric W. M.; and Huby, Pamela M. 1961 An Assessment of the Responses to Drugs Acting on the Central Nervous System. Clinical Pharmacology and Therapeutics 2:587–598.

Wolf, Stewart 1959 The Pharmacology of Placebos. Pharmacological Reviews 11:689–704.

Zubin, Joseph; and Katz, Martin M. 1964 Psycho-pharmacology and Personality. Pages 367–395 in Symposium on Personality Change, University of Texas, Personality Change. Edited by Philip Worchel and Donn Byrne. New York: Wiley.

II DRUG ADDICTION: ORGANIC AND PSYCHOLOGICAL ASPECTS

Common to all of the conditions to which the term “drug addiction” has been applied is the criterion of habitual use of chemical agents (natural or synthetic) in spite of harmful consequences to the individual, society, or both. The present article deals mainly with the organic (pharmacological and physiological) and psychological aspects of the problem, particularly with reference to the opioids.

In part, harmful consequences may arise from the pharmacological and toxicological properties of the drug employed. These vary greatly, depending on the class of drug, the dose, and regularity and frequency of administration. Thus the toxic states induced by opioids (all chemical substances with morphinelike properties, including morphine itself) are characterized by respiratory depression, stupor, or coma; barbiturates, certain nonbarbitu-rate sedatives, and alcohol can produce mental confusion, incoordination, and coma; cannabis products (marijuana, hashish), amphetamine and allied “stimulant amines,” and cocaine, as well as a number of “psychosomimetic” agents (mescaline, d-lysergic acid diethylamide), can give rise to psychoses of various sorts.

Repeated administration of opioids, barbiturates and allied drugs, or alcohol can give rise to a state of “pharmacogenic” (or “physical”) dependence— i.e., a state such that abrupt withdrawal of the drug is followed by physiological and psychological disturbances (“abstinence syndromes”), which are usually transient but may be fatal. These also differ, depending on the class of drug involved— for example, predominantly autonomic disturbances in the case of the opioids, and convulsions and delirium in the case of barbiturates, nonbarbiturate sedatives, or alcohol. Associated in varying degrees with the development of pharmacogenic dependence is the acquisition of “tolerance”—i.e., progressive decline in degree of effect produced by a given dose of the drug—which can be almost complete in opioid users but is achieved only partially by regular use of the barbiturate and allied drugs or alcohol. With the acquisition of tolerance, the user is impelled to increase progressively the dosage and/or frequency of administration in striving for the original effects, thereby incurring the risk of inducing toxic reactions and intensifying still further the degree of pharmacogenic dependence—a state that in itself has disastrous consequences for the psychological as well as the physical functioning of the user

Social consequences. In part, the harmful consequences of habitual drug use are social in nature. Even at subtoxic dose levels the effects of a given drug may impair the user’s usefulness to the society in which he lives or may otherwise modify his behavior in unacceptable ways. In addition, harmful consequences may result from the user’s attendant neglect of the welfare of his dependents, through either indifference to them, diversion of income for purchase of drugs, or adverse effects on his own health caused by inattention to proper nutrition, hygiene, and treatment of disease. Since in most societies it has been found necessary to place legal restrictions on the manufacture and distribution of many drugs of abuse, criminalism constitutes another of the consequences of this practice.

Clinical features of opioid addiction

The more commonly abused opioids include opium itself (containing 10 per cent morphine); morphine and certain of its derivatives, such as codeine, diacetylmorphine (heroin), dihydromorphinone (Dilaudid), dihydrohydroxycodeinone (eucodal); and a number of synthetic analgesics, such as meperidine (pethidine, Demerol, dolantin), ketobemidone, methadone (Dolophine, Amidone), and dextromoramide (Palfium). Heroin is the most common opioid purveyed illicitly throughout the world, although opium is still widely used in the Orient. Important variations occur, depending upon the particular opioid and the mode of utilization (smoking, sniffing, ingestion, injection), but the effects of morphine under experimental conditions are quite illustrative of the specific patterns of chronic intoxication, tolerance, and pharmacogenic dependence that develop with repeated use of opioids in general.

In nontolerant persons a single injection of a “therapeutic” dose of morphine (e.g., 15 milligrams) commonly produces a state of drowsiness from which the subject can be readily aroused. Pain, if present, is relieved and anxiety allayed. The sensorium remains intact, although some subjects may report that they feel “mentally clouded.” Contrary to popular notions, lurid fantasies are rare, and sexual desires are not increased, although in the male potency may be enhanced by delay of orgasm. Particularly if injected intravenously, morphine may produce transient sensations in the abdomen that are sometimes described as akin to orgasms. Flushing of the skin and itching, as well as giddiness and vomiting, are also common effects. Characteristically, the pupils are constricted, respiratory rate is depressed, the pulse is slowed, and body temperature is lowered slightly. These effects, which last four to six hours, may be evaluated in different ways by different subjects, depending upon circumstances, but even among future habitues the effects of the first injection of morphine (or heroin) are often judged as unpleasant.

With further experience, however, some individuals come to evaluate the constellation of effects more positively, and their observers describe the subjects as “euphoric.” With more frequent repetition, however, tolerance develops, albeit at different rates for various effects. Thus, the degree and duration of drowsiness, relief of pain and anxiety, depression of respiration, slowing of the pulse, nausea, and vomiting decrease progressively, whereas pupillary constriction and lowering of the body temperature decline at less rapid rates, and spasm of smooth muscle continues to be very pronounced with the resultant production of severe constipation. In the tolerant state, secretion of adrenocorticotrophic hormone (ACTH) by the pituitary gland is reduced, sexual interest is lost, males become impotent, and females cease to menstruate. In attempts to regain “euphoria” addicts have been known to increase the daily dose to 5,000 mg. or more, with only partial and transitory success. If the accustomed dose of morphine is then withheld, a fairly stereotyped abstinence syndrome ensues. Beginning 12—16 hours after the last dose, restlessness, anxiety, frequent yawning, rhinorrhea, lacrimation, pupillary dilation, sweating, and piloerection are noted first. In addition, muscular aches and twitches, abdominal cramps, vomiting and diarrhea, elevated blood pressure, insomnia, agitation, weight loss, spontaneous ejaculations in the male, and profuse menstrual bleeding in the female supervene later, developing maximally during the next two or three days and then subsiding gradually, although physiological normality may not be achieved for six months or longer. Such abstinence phenomena are quickly alleviated by injection of the accustomed dose of morphine (or an equivalent dose of another opioid), only to reappear some hours later. The untreated morphine abstinence syndrome is rarely fatal, except in patients with cardiac disease, active tuberculosis, or other debilitating illness.

Of clinical importance are some special features of addiction to a number of other opioids. In the case of meperidine (Demerol), myoclonic jerks or generalized convulsions (with characteristic electroencephalographic abnormalities) may occur if the total daily dose level attained in the tolerant state is over 2,000 mg. Although the over-all effects of methadone are practically identical with those of morphine, the duration of action of methadone is somewhat longer, and therefore cumulative depressant effects on the central nervous system may occur if the drug is administered several times daily. The methadone abstinence syndrome is slower in onset and milder in degree (with respect to autonomic disturbances) than that observed after withdrawal of morphine. For these reasons methadone may be substituted for morphine and other opioids of addiction in the management of drug withdrawal. Despite widespread assumptions to the contrary, neither the intensity of “euphoric” effects, the rate of development of tolerance, nor the peak intensity of the abstinence syndrome is greater for heroin than for morphine when these two drugs are administered in equipotent doses (1.80 to 2.66 mg. of morphine sulfate is equal to 1 mg. of heroin), although some opioid addicts can distinguish morphine from heroin by their subjective effects when these drugs are administered intravenously.

The diagnosis of pharmacogenic dependence on opioids can be made in two ways: (a) by observation of the abstinence syndrome that ensues when the drug is withheld; and (b ) by subcutaneous injection of a specific morphine antagonist, such as nalorphine (3–15 mg. in divided doses). With the latter procedure an “acute abstinence syndrome” may be precipitated within minutes after injection in persons addicted to any of the opioids (except possibly meperidine), the severity of which depends upon the daily dose level and duration of addiction. Experimentally it has been shown that mild abstinence phenomena, such as yawning, lacrimation, rhinorrhea, piloerection, sweating, and pupillary dilatation, can be precipitated by subcutaneous injection of 15 mg. of nalorphine in persons who have been receiving as little as 15 mg. of morphine four times daily for two or three days or equivalent doses of heroin or methadone on the same schedule.

Treatment

Wikler (1962) provides the details of treatment. Evaluation of the results of treatment has been extremely difficult. The best evidence available, that of a large group of addicts returning to New York after treatment at the U.S. Public Health Service Hospital in Lexington, Kentucky, indicates that over 90 per cent of the patients became addicted again, more than 90 per cent of these within six months after their discharge (Hunt & Odoroff 1962, p. 53). On the other hand, there is some evidence suggesting that opioid addiction may run a self-limiting course after a number of years. Thus, it has been found that at the end of five years of follow-up, 25 per cent of a sample of the group described above were “voluntarily abstinent,” and attention has been directed to the “35–40 age drop-off” in names of “active addicts” in the files of the Bureau of Narcotics. This phenomenon requires further evaluation.

Organic aspects of opioid addiction

Physical characteristics of addicts

In a study of four hundred opioid addicts (Caucasian) at the U.S. Public Health Service Hospital, Lexington, Brown (1940) found them to be of average or slightly superior height and weight, with normal distribution of body build, although there was a trend toward the pyknic habitus. Electroencephalo-graphic studies by Andrews (1941) on fifty addicts (one year after drug withdrawal) revealed only that the groups differed from published data on “normals,” in that among the addicts, individuals with occipital alpha indices either of 90–100 per cent or of 0–10 per cent were more common. These deviations from “normal” have no known clinical significance. In the personal experience of the author, there are no physical traits or diseases among opioid addicts in the United States that distinguish them from nonaddicts except for those consequent to drug abuse, such as cutaneous scars and pigmentations, phlebosclerosis, and a relatively high incidence of systemic infectious diseases (malaria, bacterial or mycotic endocarditis) resulting from use of contaminated needles and more common diseases allowed to progress through neglect. No irreversible organic damage to the nervous system or viscera is known to occur as a result of opioids per se.

Effects of single doses of opioids

Since one of the major actions of morphine and other opioids is the production of analgesia, it might be supposed that these drugs block transmission or otherwise exert depressant effects somewhere in the direct sensory pathways presumed to mediate pain. How-ever, the evidence bearing on this supposition is far from conclusive. In the cat morphine prolongs recovery time of interneurons in the thalamic “relay” nuclei (responding to electrical stimulation of the sciatic nerve), but in the dog morphine does not depress amplitude or latency of responses, evoked by electrical stimulation of the tooth pulp, in the contralateral coronal gyrus, the contralateral nucleus ventralis posteromedialis, or the medial lemniscus. Apart from the question of species differences, resolution of this problem is complicated by uncertainty about the specific modalities of sensation that are activated by the stimuli used in animal research on pain and analgesia. In this regard, electrical stimulation of the tooth pulp would seem to be the least ambiguous. Tentatively, therefore, it may be assumed that actions on the direct pain pathways cannot account for the analgesic effects of these drugs.

Insofar as the “indirect” sensory pathways are concerned, a depressant action of morphine on the ascending midbrain reticular “arousal” mechanism has been found in the rat and the rabbit, but in the case of the cat the evidence is conflicting. In both the rabbit and the dog morphine enhances recruiting responses evoked by stimulation of thalamic intralaminar nuclei, but in the cat such responses are said to be depressed. These discrepancies may perhaps be related to the differences in general behavioral effects of morphine in the rabbit and dog (depression) on the one hand and the cat (excitation) on the other. In the dog, however, the effects of morphine on potentials evoked in the “indirect” pathways by stimulation of tooth pulp were found to be exceedingly complex, augmentation as well as depression or no effect being observed in different components of this system. In any case, the relevance of these data to the problem of morphine analgesia is open to question because the “indirect” pathways are selectively affected by small doses of barbiturates and other drugs that are not classified as analgesics.

Effects on reflex activity. More consistent, and perhaps more relevant to the problem of analgesia, are the effects of morphine on certain reflex activities at various segments of the neuraxis. Thus, in adequate doses, morphine depresses “sham rage” in decorticated cats and dogs, flexor and crossed extensor reflexes in spinal cats and dogs, the flexor reflex in spinal man, and mandibular response to stimulation of the tooth pulp in dogs. In addition, morphine exerts depressant actions on the “skin-twitch” in the dog and the “tail-flick” in the rat, both of which have been used successfully in the screening of drugs for analgesic properties in man. In part, morphine affects these reflexes by a direct depressant action of spinal interneurons, but a major component of its action in the intact animal appears to be augmentation of supraspinal inhibition. From the neurophysiological standpoint, therefore, it would appear that morphine alters the “reaction” to noxious stimulation at several levels of the neuraxis rather than affecting propagation of impulses generated by such stimuli from the periphery to the cerebral cortex. However, there is no reason to assume that the selective actions of morphine on nociceptive reflexes are related solely to the analgesic actions of this drug. In fact, it may be that what is termed “morphine analgesia” merely refers to the component of the total pattern of effect produced by this drug (indifference to ordinarily painful conditions, drowsiness, “euphoria”) that interests the clinician under a given set of circumstances. As Schaumann (1954) has pointed out, the analgesic action of morphine is but part of its “antiprotective” spectrum of effects —quite similar to the concept “primary-need reducing,” which has also been applied in this connection (Wikler 1952).

Sites of morphine action. Much research has also been devoted to the problem of accounting for the selectivity that characterizes the sites of action of morphine in the central nervous system. In isolated smooth muscle preparations, morphine has been shown to reduce both the resting output of acetylcholine and the output from postganglionic cholinergic nerve endings when they are stimulated, and to inhibit the release of sympathetic transmitter substance from postganglionic nerve endings in rats. It was found that single doses of morphine decrease the brain concentrations of norepinephrine, but repeated administration of morphine increases these concentrations. The possible significance of this finding will be discussed further in connection with the mechanisms of pharmacogenic dependence.

Chronic effects

Not only have abstinence phenomena been observed in babies born of mothers addicted to opioids, but tolerance to many of the effects of opioids after repeated administration of these drugs and clear-cut abstinence phenomena following their abrupt withdrawal have been demonstrated in intact monkeys, dogs, and rats, in long-surviving decorticated dogs, in chronic spinal dogs, in a chronic spinal man, and even in unicellular organisms and tissue cultures. It has also been reported that in vitro, cortical slices from brains of rats treated with morphine daily for one week exhibit tolerance to the depressant effects of morphine on respiration (oxygen consumption) stimulated by potassium chloride. Since there is no evidence that the development of tolerance to opioids is associated with an increased capacity of the organism to destroy the drug (Woods 1954) or that “immune” or “antimorphine” circulating substances are formed during chronic morphine intoxication, these findings suggest a cellular site of origin for both tolerance and pharmacogenic dependence. Presumably, such cellular processes involve changes in enzymatic activity, but the identity of the enzymes concerned is not yet known.

Axelrod (1956a; 1956b) found that in rats the development of tolerance to morphine is associated with progressive decrease in the capacity of the liver to N-demethylate this drug, as well as other agents with morphinelike actions, and that chronic administration of N-allylnormorphine with morphine reduces both the rate of development of tolerance to morphine and the decrease in N-demethylating capacity of the liver in this species. Using the hepatic N-demethylating enzyme system as a model for the study of tolerance, it was suggested that a decreased response to narcotic drugs on repeated administration may develop as a result of unavailability of receptor sites, due to deactivation of these sites through continuous interaction with opioids. Other data suggest that enzyme systems concerned with the metabolism of catecholamines may be critically involved in the genesis of the abstinence syndrome. In the rat brain concentration of catecholamines is supranormal during chronic morphine intoxication. It has also been reported that in both the dog and the rat urinary excretion of catecholamines is markedly increased during the acute abstinence period. At the present time the precise manner in which these changes are related to pharmacogenic dependence is difficult to establish because of some differences in regard to details that depend on the species used and the techniques employed by different investigators.

Although the phenomena of tolerance and pharmacogenic dependence appear to be due to changes at the cellular level, it is quite likely that certain features of the clinical opioid abstinence syndrome are modulated by “counteradaptive” changes involving systems not directly affected, or only slightly affected, by this class of drugs.

Electroencephalograms of addicts “stabilized” on morphine are characterized by abnormally high alpha output, with marked slowing in some cases, but the electroencephalogram returns to the control (normal or high alpha index) pattern promptly after abrupt withdrawal of the drug (Andrews 1941)—a surprising finding in view of the intense autonomic and emotional disturbances that occur during the early abstinence period. In man, bilateral prefrontal lobotomy has little effect on the “nonpurposive” features of the morphine abstinence syndrome (preponderantly autonomic) but does attenuate “purposive” abstinence phenomena, such as “craving” and drug-seeking behavior (Wikler et al. 1952). In monkeys experimentally addicted to morphine, bilateral section of the cingulum (a fiber bundle connecting the frontal cortex with the limbic system) does attenuate the morphine abstinence syndrome (Foltz & White 1957), but certain details of the findings (White 1953) suggest that in this species also the “attenuating” effects of the operative procedure were exerted mainly upon withdrawal signs analogous to human “purposive” abstinence phenomena. Removal of facilitatory frontal cortical influences on subcortical autonomic centers may also have contributed to the “attenuation” of the simian morphine abstinence syndrome as a whole. In addition, it appears that at least in man the hypothalamic-pituitary system is depressed during maintained morphine addiction and becomes hyperactive during the acute phase of the abstinence syndrome, Eisenman, Fraser, Sloan, and Isbell (Eisenman et al. 1958) having shown that during chronic morphine intoxication, urinary excretion of 17-ketosteroids is significantly depressed although the adrenal glands remain responsive to ACTH. In contrast, both plasma levels and urinary excretion of 17-ketosteroids increase far above control values after abrupt withdrawal of morphine, along a time course roughly parallel to that of the acute abstinence syndrome. Further studies on animals are needed to determine whether these endocrinal changes are consequent to changes in neural activity during chronic morphine intoxication and during the abstinence period, or whether the reverse is the case.

Of special importance to theories of opioid addiction and relapse are data acquired with the use of N-allylnormorphine (nalorphine), a specific morphine antagonist. As has already been noted, this agent is capable of precipitating clear-cut abstinence phenomena in man after four-times-daily administration of “therapeutic” doses of morphine, heroin, or methadone for as brief a period as two or three consecutive days. Martin and Eades (1961) have shown that in dogs nalorphine can precipitate fairly severe abstinence phenomena when given in a single subcutaneous dose (20 mg./kg.) within 15 minutes after termination of a single continuous intravenous infusion of morphine at the rate of 3 mg./kg. per hour for 7.5 to 8 hours. In addition, it was demonstrated that such animals had developed a considerable degree of tolerance to several of the effects of morphine during the single continuous infusion of the drug. It is probable, therefore, that the processes of tolerance and pharmacogenic dependence begin to develop in man with the first dose of morphine even though these changes may not be clinically detectable. Also, evidence is accumulating that full recovery from the morphine abstinence syndrome may require much longer periods of time than has heretofore been believed. As has already been noted, minor but persistent deviations from normal have been detected in man for as long as six months after withdrawal from morphine following a period of addiction (Himmelsbach 1942). Martin, Wikler, Eades, and Pescor (Martin et al. 1963) have demonstrated that in the rat an early “primary” phase of the morphine abstinence syndrome is succeeded by a “secondary” phase, lasting over six months, during which the morphine-abstinent rat continues to display mild but definite signs of hyperirritability in comparison with concurrently observed control rats.

Psychological aspects of opioid addiction

Personality characteristics of addicts

The most extensive studies on the personality characteristics of opioid addicts are those which have been conducted over a period of about twenty years on the population of the U.S. Public Health Service Hospital in Lexington. Although other characteristics of this population have undergone changes in the course of two decades (shift in racial distribution from predominantly white to predominantly Negro, increase in proportion of patients from large metropolitan centers, and decrease in median age), the large majority of individuals that constitute this population have consistently been classified as “psychopathic.” Thus, on the basis of their study with the Minnesota Multiphasic Personality Inventory (MMPI) on 270 subjects, Hill, Haertzen, and Glaser (1960) concluded that narcotic addicts are often psychopathic, that hospitalized adolescent and adult addicts do not differ in their MMPI profiles, that great similarities exist between adolescent addicts and delinquent nonaddicts, and that psychopathology is an important etiological element in addiction (p. 138).

However, very similar MMPI profiles have also been found by this group of investigators to characterize not only juvenile delinquents but also hospitalized chronic alcoholics (Hill, Haertzen, & Davis 1962). Speculating on the commonness of elevated scores for psychopathy in the MMPI among narcotic (opioid) and alcoholic subjects, Hill (1962) has suggested that the “social deviant” does not engage in the daily activities that are ordinarily reinforced by and satisfy the larger society. Counteranxieties and inhibitions that deter unusual behavior in the mature adult do not do so in the social deviant. Thus, he is particularly vulnerable to short-term satisfactions and can readily manipulate his personal affairs if drugs are available (p. 573). The deviant who is immature and inadequate and is unable to solve problems of adult life independently may find temporary freedom from frustration and problems in alcohol or complete elimination of such problems in opiates (p. 578).

Other investigators have stressed “passive dependency” as a dominant trait among opioid addicts, and Wikler and Rasor (1953) have suggested that such individuals choose opioids for repeated use from among a number of other drugs, including alcohol, with which they have had experience precisely because the opioids facilitate their preferred mode of dealing with frustrating and anxiety-arousing situations—namely, by promoting “indifference” to them rather than by increasing aggressiveness, as would the use of alcohol. however, a major difficulty in relating personality characteristics found in opioid addicts to the addiction process is the paucity of suitable control data. Gerard and Kornetsky (1955) compared the personalities of 32 young addicts treated at the Lexington Hospital with those of 23 nonaddict acquaintances named by addicts who were undergoing treatment at another hospital. They concluded that although the addicts were more disturbed (with a high incidence of overt or incipient schizophrenia), about half of the control group also showed evidence of significant psychiatric disorder. Further research in this area, especially on the personality characteristics of parents and siblings of opioid addicts, may help clarify many questions about the relation between personality characteristics and addiction that are still unanswered.

Single doses of opioids

Whether the nontolerant opioid addict is more susceptible to morphine “euphoria” than the nonaddict individual is a question of considerable importance for the dynamics of addiction. Lasagna, Von Felsinger, and Beecher (1955) compared the effects on mood of single doses of placebo, amphetamine, pentobarbital, morphine, and heroin in a group of “postaddict” prisoners and a group of normal volunteers, as well as another group of chronically ill patients. As expected, these investigators found that heroin produced the greatest incidence of “euphoric” effects in the postaddicts, but only a few individuals in the other groups responded to either morphine or heroin in this manner. In another study on the volunteer group alone, Von Felsinger, Lasagna, and Beecher (1955) obtained data on personality dynamics indicating that typical or atypical reactions to the drugs used in the previous study could be correlated with differences in mature controls and emotionality (p. 1119). However, it is difficult to evaluate the significance of these findings for the addiction process because the postaddict and non-addict groups in the study of Lasagna, Von Felsinger, and Beecher (1955) differed in ways other than presumed personality structures (prior experience with drugs, sociolegal status). In further studies on normal subjects, Smith and Beecher (1959) found that morphine (10 mg./70 kg.) produced a variety of unpleasant subjective effects, among which “mental clouding” was especially prominent.

As judged by objective performance tests, however, the mental impairment produced by small single doses of opioids would seem to be much less than is implied by the term “mental clouding.” Bauer and Pearson (1956) studied the performance of 96 nonaddict male subjects on a difficult perceptual-motor task involving manipulation of throttle, stick, and rudder controls to compensate random movements of four instrument pointers from the null position and found that the effects of 8 mg. of morphine could not be differentiated from those of placebo (saline) injections. Kornetsky, Humphries, and Evarts (1957) reported that 100 mg. of meperidine produced only a slight and nonsignificant impairment of performance on a variety of mental tests of nonaddict individuals. Smith, Semke, and Beecher (1962) did find that single doses of morphine (10 mg./70 kg.) or heroin (4 mg./70 kg.) produced significant impairment of performance on a number of tests of mental function but noted that the impairment was primarily one of speed rather than accuracy. Studies with comparable techniques have not been made in postaddicts, but the earlier studies of Brown (1946) suggest that the effects of opioids relevant to the addiction process lie in the “emotional” area rather than in “cognitive” functioning. Thus, in a long-term study on two postaddicts during experimental readdiction to morphine, he found that although this drug did produce a mild degree of impairment of performance on code learning, continuous subtraction, and immediate and delayed recall of nonsense syllables, as well as on the speed of voice and hand responses to word stimuli, the most striking effect was the reduction of differences in speed between voice responses to “indifferent” word stimuli and those to “disturbing” word stimuli (drugs, sex, and crime), suggesting the possibility that morphine might alleviate the disturbances of personal and social conflicts. Such circumstances might be the reason for morphine addiction and relapse after periods of abstinence (p. 52). In addition, Brown (1943) found that Rorschach responses of postaddicts were generally “constricted” and immature; single doses of morphine reduced the degree of constriction and increased the occurrence of fantasy and human movement responses.

Other data on the “emotional” effects of morphine have been obtained by Hill and others in a series of studies on “anxiety associated with the anticipation of pain” in postaddicts. Noting that the effects of single doses of morphine on the so-called pain threshold are unpredictable (Andrews 1943; Denton & Beecher 1949), these investigators hypothesized that one important action of morphine in the production of analgesia is dissociation of “anxiety” from perception of the noxious stimulus. In agreement with this hypothesis, others found that morphine (15 mg.) had no significant effect on the ability of postaddicts to estimate intensities of brief but painful electric shocks under “nonanxious” conditions; under “anxious” conditions untreated subjects overestimated the intensity of such stimuli, whereas after injection of morphine the estimated and actual intensities of these stimuli did not differ significantly. Likewise, it has been reported that single doses of morphine (15 mg.) significantly reduced the disruption of performance on a visual-manual reaction time test, produced by repeated self-inflicted electric shock penalties for “slow” reaction times—an action not shared by pentobarbital (250 mg.). Further evidence of the effectiveness of morphine in reducing “anxiety associated with anticipation of pain” was obtained by Kornetsky (1954) in a study on post-addicts, employing radiant heat stimuli instead of electric shocks. In addition to measurement of “stronger or weaker than standard” judgments of the noxious stimulus, several measures of “anticipation” were included, under both “anxious” and “nonanxious” conditions. It was found that morphine decreased significantly the number of “stronger” responses, as well as anticipatory psychogalvanic responses, only under “anxious” conditions.

That reduction of “anxiety associated with anticipation of pain” may be but one example of a more general effect of morphine on “motivation” is suggested by the results of another study by Hill, Belleville, and Wikler (1957) on postaddicts. In this study, visual-manual reaction times were measured under four different incentive conditions (defined as such in terms of different schedules of morphine rewards for participation in the experiments) in untreated subjects, one hour after administration of morphine (15 mg.), and after intramuscular injection of 250 mg. of pentobarbital. In untreated subjects mean reaction times varied from “slow” to “fast,” depending upon the incentive condition under which they were measured. Morphine significantly reduced the “range of change,” while pentobarbital had the opposite effect. It would thus appear that, at least in post-addicts, single doses of morphine reduce responsivity to a variety of stimuli that have in common the property of producing “emotional” arousal.

Chronic effects

Although morphine-produced “euphoria” would seem to be a decisive factor in reinforcing repeated use of this drug, the rapid development of tolerance to this effect results in marked changes in the behavior of the addict. Thus, Brown (1946), in his long-term study on experimental readdiction in two subjects, noted that there was seldom a level of dosage that maintained satisfaction for a period longer than three weeks. There were no signs that morphine had increased the general sense of pleasantness, although there were short periods of euphoria. The general mood level during the period of addiction was one of un-pleasantness (p. 42). Similar observations were made by Wikler (1952) in a study on self-regulated experimental readdiction to morphine in a single postaddict. Over a period of three and a half months this subject progressively increased the size of each dose and the frequency of self-injections (intravenous) to a total daily dose level of about 1,350 mg. of morphine taken in 12 divided doses throughout the day and night. Nevertheless, he was unable to regain the euphoric effects he had experienced initially after a single dose of 30 mg. of morphine, and his prevailing mood was one of dejection, remorse, guilt, and anxiety, which were also reflected in his dream material. The experimental arrangements provided for self-reduction of the dose of morphine and eventual withdrawal by the methadone substitution method whenever the subject might request such treatment, but he gave no evidence of entertaining such an idea at any time before the date of the termination of the study, of which, by prior agreement, he received one month’s notice. In the absence of “euphoria,” the subject’s persistence in self-administration of morphine was difficult to explain, but a striking feature of his “free associations” was the frequency with which he compared craving for morphine with hunger and the relief of craving with satiation. It appeared, therefore, that instead of being a deterrent, the physical dependence brought about by repeated morphine injections seems to be one of the drug’s attractive attributes, since it is a new source of gratification. The new pharmacogenic need may in some cases become strong enough to displace other primary needs.

In terms of instrumental conditioning theory, this inference can be restated as the proposition that in the state of pharmacogenic dependence, drug-acquisitory behavior is reinforced by the efficacy of opioids in reducing the drive engendered by early abstinence phenomena following the last previous dose of the drug. There is evidence that such, indeed, may be the case and also that reinforcement resulting from reduction of abstinence phenomena may outlast the acute (“primary”) abstinence period. However, as Martin, Wikler, Eades, and Pescor (Martin et al. 1963) have demonstrated, the “primary,” or acute, abstinence syndrome is succeeded by a long-enduring “secondary” abstinence syndrome (six months or more) in the rat, and therefore the possibility cannot be excluded that such evidence of “relapse” is based upon persistence of “unconditioned” abstinence phenomena that are relieved by morphine.

To account for “late” relapse, Wikler (1948) suggested that under certain circumstances morphine abstinence phenomena may become conditioned in the classical manner during periods of pharmacogenic dependence and may therefore reappear as conditioned responses long after complete subsidence of the abstinence syndrome following withdrawal of the drug. Some experimental evidence that such conditioning is possible has been acquired in studies on the rat, and Wikler (1961; 1965) has proposed a “two-factor learning theory” of relapse, in which classical conditioning of the abstinence syndrome is postulated as the basis for recurrence of a drive state similar to that operating during previous episodes of addiction, and operant conditioning, also taking place during previous episodes of pharmacogenic dependence, is postulated as the basis for renewed drug-acquisitory behavior long after “cure.” In addition, Wikler has suggested (1955) that an important factor in relapse may be “the need for continuous activity directed toward attainable, but recurring goals” (p. 567), which, in the case of the addict, is furnished by pharmacogenic dependence on opioids. That such “hustling” activity is highly valued by opioid addicts is suggested by their preoccupation with this topic even when confined in an institution. Viewed as an “effort” variable, “hustling” may increase resistance to extinction of drug-acquisitory behavior.

Although the various roles assigned to pharmacogenic dependence are still highly speculative, they would seem to deserve intensive research, since one obvious fact about “drug addiction” in general is that the drugs which create the most persistent degrees of “habitual use with harmful consequences” are precisely those which engender pharmacogenic dependence.

Abraham Wikler

[Other relevant material may be found inDrinking and alcoholismandSmoking.]

BIBLIOGRAPHY

Andrews, H. L. 1941 Brain Potentials and Morphine Addiction. Psychosomatic Medicine 3:399–409.

Andrews, H. L. 1943 The Effects of Opiates on the Pain Thresholds in Post-addicts. Journal of Clinical Investigation 22:511–516.

Axelrod, Julius 1956a The Enzymatic N-Demethylation of Narcotic Drugs. Journal of Pharmacology and Experimental Therapeutics 117:322–330.

Axelrod, Julius 1956b Possible Mechanism of Tolerance to Narcotic Drugs. Science New Series 124:263–264.

Bauer, Robert O.; and Pearson, Richard G. 1956 The Effects of Morphine-Nalorphine Mixtures on Psycho-motor Performance. Journal of Pharmacology and Experimental Therapeutics 117:258–264.

Brown, R. R. 1940 The Relation of Body Build to Drug Addiction. Public Health Reports 55:1954–1963.

Brown, R. R. 1943 The Effect of Morphine Upon the Rorschach Response Pattern in Post-addicts. American Journal of Orthopsychiatry 13:339–342.

Brown, R. R. 1946 A Cycle of Morphine Addiction: biological and Psychological Studies. Part 2: Psychological Investigations. Public Health Reports 61:37–53.

Denton, Jane E.; and Beecher, Henry K. 1949 New Analgesics. Journal of the American Medical Association 141:1051–1057; 1146–1153.

Eisenman, Anna J. et al. 1958 Urinary 17-Ketosteroid Excretion During a Cycle of Addiction to Morphine. Journal of Pharmacology and Experimental Therapeutics 124:305–311.

Foltz, Eldon L.; and White, Lowell E. 1957 Experimental Cingulumotomy and Modification of Morphine Withdrawal. Journal of Neurosurgery 14:655–673.

Gerard, Donald L.; and Kornetsky, Conan 1955 Adolescent Opiate Addiction: A Study of Control and Addict Subjects. Psychiatric Quarterly 29:457–486.

Hill, Harris E. 1962 The Social Deviant and Initial Addiction to Narcotics and Alcohol. Quarterly Journal of Studies on Alcohol 23:562–582.

Hill, Harris E.; Belleville, R. E.; and Wikler, Abraham 1957 Motivational Determinants in the Modification of Behavior by Morphine and Pentobarbital. A.M.A. Archives of Neurology and Psychiatry 77:28–35.

Hill, Harris E.; Haertzen, Charles A.; and Davis, Howard 1962 An MMPI Factor Analytic Study of Alcoholics, Narcotic Addicts and Criminals. Quarterly Journal of Studies on Alcohol 23:411–431.

Hill, Harris E.; Haertzen, Charles A.; and Glaser, Robert 1960 Personality Characteristics of Narcotic Addicts as Indicated by the MMPI. Journal of General Psychology 62:127–139.

Himmelsbach, C. K. 1942 Clinical Studies of Drug Addiction: Physical Dependence, Withdrawal and Recovery. Archives of Internal Medicine 69:766–772.

Hunt, G. Halsey; and Odoroff, Maurice E. 1962 Followup Study of Narcotic Drug Addicts After Hospitalization. U.S. Public Health Service, Public Health Reports 77:41–54.

Kornetsky, Conan 1954 Effects of Anxiety and Morphine on the Anticipation and Perception of Painful Radiant Thermal Stimuli. Journal of Comparative and Physiological Psychology 47:130–132.

Kornetsky, Conan; Humphries, Ogretta; and Evarts, Edward V. 1957 Comparison of Psychological Effects of Certain Centrally Acting Drugs in Man. A.M.A. Archives of Neurology and Psychiatry 77:318–324.

Lasagna, Louis; Von Felsinger, John M.; and Beecher, Henry K. 1955 Drug-induced Changes in Man: 1. Observations on Healthy Subjects, Chronically 111 Patients and “Postaddicts.” Journal of the American Medical Association 157:1006–1020.

Martin, W. R.; and Eades, C. G. 1961 Demonstration of Tolerance and Physical Dependence in the Dog Following a Short-term Infusion of Morphine. Journal of Pharmacology and Experimental Therapeutics 133: 262–270.

Martin, W. R. et al. 1963 Tolerance to and Physical Dependence on Morphine in Rats. Psychopharmacologia 4:247–260.

Schaumann, O. 1954 Analgetika und protektives System. Deutsche medizinische Wochenschrift 79:1571–1573.

Smith, Gene M.; and Beecher, Henry K. 1959 Measurement of “Mental Clouding” and Other Subjective Effects of Morphine. Journal of Pharmacology and Experimental Therapeutics 126:50–62

Smith, Gene M.; Semke, Charles W.; and Beecher, Henry K. 1962 Objective Evidence of Mental Effects of Heroin, Morphine and Placebo in Normal Subjects. Journal of Pharmacology and Experimental Therapeutics 136:53–58.

Von Felsinger, John M.; Lasagna, Louis; and Beecher, Henry K. 1955 Drug-induced Changes in Man: 2. Personality and Reactions to Drugs. Journal of the American Medical Association 157:1113–1119.

White, L. E. Jr. 1953 Attenuation of the Morphine Abstinence Syndrome of the Addicted Monkey (Macaca Mulatta) by Lesions in the Anterior Cingulate Gyrus. Ph.D. dissertation, Univ. of Washington (Seattle).

Wikler, Abraham 1948 Recent Progress in Research on the Neurophysiologic Basis of Morphine Addiction. American Journal of Psychiatry 105:329–338.

Wikler, Abraham 1952 A Psychodynamic Study of a Patient During Experimental Self-regulated Re-addiction to Morphine. Psychiatric Quarterly 26:270–293.

Wikler, Abraham 1955 Rationale of the Diagnosis and Treatment of Addictions. Connecticut State Medical Journal 19:560–568.

Wikler, Abraham 1961 On the Nature of Addiction and Habituation. British Journal of Addiction 57:73–79.

Wikler, Abraham 1962 Drug Addiction. Volume 8, pages 17–58 in Frederick Tice (editor), Practice of Medicine. Hagerstown, Md.: Prior.

Wikler, Abraham 1965 Conditioning Factors in Opiate Addiction and Relapse. Pages 85–100 in D. Wilner and G. G. Kassebaum (editors), Narcotics. New York: McGraw-Hill.

Wikler, Abraham et al. 1952 The Effects of Frontal Lobotomy on the Morphine Abstinence Syndrome in Man: An Experimental Study. A.M.A. Archives of Neurology and Psychiatry 67:510–521.

Wikler, Abraham; and Rasor, Robert W. 1953 Psychiatric Aspects of Drug Addiction. American Journal of Medicine 14:566–570.

Woods, L. A. 1954 Distribution and Fate of Morphine in Non-tolerant and Tolerant Dogs and Rats. Journal of Pharmacology and Experimental Therapeutics 112: 158–175.

III DRUG ADDICTION: SOCIAL ASPECTS

The taking of drugs is culturally patterned behavior. Both the prevalence and the consequences of drug use in any society depend as much upon social norms as upon physiological responses to drugs or general psychological characteristics of drug users. The ends sought through use of drugs are varied: relief from pain, fatigue, or anxiety, the celebration of social solidarity, “kicks,” and enhanced mystical experience. Beliefs about the effects of the substances used and the specific ends sought through such use are closely linked with more general cultural goals and orientations. A particular drug—for example, marijuana (also called hashish and bhang)—may be accepted as an appropriate adjunct to sociability in one society, used as an invaluable ingredient in religious contemplation in another, and banned by law as dangerous in a third.

There is no evidence that addiction to drugs is favorably regarded in any society or culture, but the status accorded the addict varies markedly. In the United States he has been defined as a criminal and stereotyped as a “dope fiend.” In much of Europe, on the other hand, the addict is regarded as an unfortunate person whose problem is primarily psychological and medical. Having stated that great differences exist in cultural orientations to specific drugs or drug effects, we are, however, far from being able to explain them. Opium and hashish have been widely used without extreme devaluation in Muslim society, although the Koran proscribes the use of substances that alter the state of consciousness. In traditional interpretations, it appears that the Koran’s injunction has been limited to alcohol.

To cite another example, a student of culture and personality has suggested that opium smoking was prevalent in China because it afforded a means of achieving the cultural goal of individual harmony with the environment. But opium smoking did not exist in China until it was introduced by European traders in the seventeenth century (Sonnedecker 1963, p. 16). Opium was subsequently forced upon the Chinese by the East India Company, despite protests by the Chinese government. An adequate understanding of drug use within a given culture requires a knowledge of historical facts that is seldom available.

To the extent that the beliefs and practices surrounding drug use reflect different perspectives and value orientations, the social correlates and the consequences of drug use will themselves vary substantially from one country to another and from time to time within any given country. Coffee and tobacco have, in various societies, been proscribed as debilitating or debauching; the smoking of tobacco was a crime punishable by death in Russia, Persia, Turkey, and parts of Germany (Lewin 1924). The term “drug” refers to a wide variety of chemical substances consumed by man, not merely to narcotics or “dangerous drugs.” When applied to substances consumed outside of medical channels, however, “drug” tends to connote something negatively valued. Hence, we do not normally apply the term “drug habit” to the smoking of tobacco, but we do to the smoking of marijuana (a non-addicting drug produced from the hemp plant), even though many more persons may be psychologically habituated to tobacco smoking than to marijuana. Because of common usage, this article is primarily concerned with narcotics addiction.

Historical background

From the earliest record in antiquity through the Middle Ages, it appears that the primary use of opium was medical. The letters and records of European travelers in the Orient during the Middle Ages occasionally refer to opium as a drug used by the people to overcome fatigue, but they do not mention chronic intoxication or indicate recognition of the phenomena of tolerance and dependency (Sonnedecker 1963, p. 16). Available records suggest that opium consumption was not a widespread practice or problem anywhere until the beginning of the seventeenth century, when opium smoking was introduced into China. Although the pleasures of opium smoking and opium eating were extolled by writers like De Quincey and Coleridge in the nineteenth century, in general neither the British nor other Europeans were drawn to opium; it was primarily an article for trade with alien peoples.

Drug use in the United States

Attitudes were in general no more favorable in the United States than in Europe, but for several reasons opiate addiction was a more frequent occurrence in the former (Terry & Pellens 1928, pp. 66–90). Among these was the reliance on patent medicines containing opium and its derivatives. Such medicines were widely used in nineteenth-century America to combat a variety of ailments, especially “female disorders.” Another source of addiction in the United States was the excessive use of hypodermically administered morphine in medical practice. Many soldiers wounded in the Civil War became addicts. Of quite a different nature was the third general influence, the introduction of opium smoking by devotees of the sporting world on the west coast in the last quarter of the nineteenth century. In this instance, opium was used purely for pleasure.

Although strongly disapproved of by the conventional citizenry (local legislation against opium dens became widespread), the practice was taken up by many persons on the fringes of polite society, and it flourished among prostitutes and underworld characters. Imports of smoking opium generally exceeded 100,000 pounds a year between 1880 and 1909, when they were finally cut off. As a consequence of these influences, opium consumption tripled in the period from 1870 to 1909. Simultaneously, the image of the addict changed rapidly as opium use became more widespread in the underworld (Eldridge 1962, pp. 9–10). Prior to the enactment of the Harrison Act, most users of narcotics were, however, conventional members of society.

The Harrison Act, passed by Congress in 1914, was basically designed to eliminate the nonmedical use of narcotics by providing controls and a careful system of accounting for and taxing all drugs defined as addicting that were produced or im ported into the United States. With the enforcement of this act, as interpreted by the narcotics section of the Treasury Department, an addict could no longer secure drugs legally. In the first two decades after passage of the Harrison Act, the number of addicts in the United States markedly declined. Since then, however, a persistent problem of somewhat changing character has emerged in the United States.

Extent of drug addiction

The extent of drug use and drug addiction, historically or currently, is known only in very general terms. Since the use of opiates and of marijuana and the so-called “dangerous drugs” is devalued by the great mass of the population in Western society, and since the possession of these drugs is illegal in many countries, it is not possible to get a direct count of drug users but only an indication of those who come to official attention in one way or another. An ad hoc panel on drug abuse reported in 1962 that discrepancies between estimates provided by federal, state, and local enforcement agencies and other sources of data were so great that they precluded any adequate estimate of the number of addicts in the United States (White House Conference 1963, pp. 290–292).

The Federal Bureau of Narcotics, which has attempted to maintain a register of “active addicts,” listed therein nearly fifty thousand names. There is no way, however, of knowing how many of the persons so listed are actively addicted at any given time or, indeed, how many are still living. From various fragments of available data, it appears that the number of persons in the United States actively addicted to opiates within the past decade is almost certainly not less than 50,000 and probably not more than 100,000. By contrast, it does not appear that any other Western country has as many as five thousand opiate addicts, according to a review of foreign experience by the Joint Committee on Narcotics of the American Bar Association and the American Medical Association (Joint Committee 1961, pp. 121–153).

Great Britain has long reported an addict population of between three hundred and four hundred. None of the Scandinavian countries has more than a few hundred addicts, nor does France or Italy. Only in West Germany does the number of known addicts go much higher, and even there the estimate is well under five thousand (Joint Committee 1961, p. 151).

Among Western countries, a significant fraction of all addicts is found among physicians and other medical personnel. Beyond this fact, very little is known about the social characteristics of drug users and addicts except for the United States. Because the problem is more prevalent in the United States than in any other Western country, and because in recent years detailed studies have been undertaken to establish the characteristics of drug users, the following discussion of patterns of drug use and of characteristics of drug users will be confined almost entirely to the United States.

Changing character of drug use

When the Harrison Act was passed, drug addicts were widely dispersed in American society. Impressions of the dominant characteristics of the addict population varied according to the segment of the population seen in treatment—highly successful individuals, middle-class neurotics, criminals, and degenerates (Terry & Pellens 1928, pp. 513–516). It seems probable that female addicts outnumbered male addicts at the turn of the century. Moreover, the large majority of addicts were native-born whites of mature years. In the following two decades, the new addicts were largely white males. Most of them were introduced to drug use as young adults already somewhat detached from conventional society. They tended to frequent or to take up residence in areas in which illegal drugs could be purchased, chiefly the most disorganized areas of the largest cities (Dai 1937). These were areas characterized by overcrowding, high rates of crime, and other social problems; they were areas that afforded anonymity in the pursuit of illicit activity.

Drug use and minority group status. By the early 1950s, many of the areas in which illicit narcotics had long been available were occupied by new waves of migration from the southeast section of the United States, from Puerto Rico, and from Mexico. The new residents were at a considerable disadvantage economically and were poorly equipped to cope with the demands of an industrial society. Many adolescents and young adults were exposed to the availability of marijuana and heroin in their home neighborhoods. Opportunities for drug use were afforded, whether or not the individual was favorably oriented toward drug use. In some neighborhoods, as many as 10 per cent of all males in late adolescence were officially recorded as drug users (Chein et al. 1964, pp. 40–41).

In recent years nearly three-fourths of all addicts recorded on the register of the Bureau of Narcotics have been Negro, Puerto Rican, or Mexican-American in extraction. One-third of these recent drug users have been under 25 years of age. Thus there has been a marked shift in the character of the problem of drug addiction in the United States in recent years; it is now entwined with minority group status. While the psychological needs and frustrations of minority group members undoubtedly contribute to the attractiveness of drugs, addiction among them cannot be adequately explained or dealt with in terms of individual psychology.

Becoming a drug user

It is obvious that narcotics must be available before there can be narcotics users; it is perhaps less obvious that an individual must learn the techniques of drug use and to some degree the proper way to perceive and enjoy drug effects before he becomes a regular drug user. The process of becoming a user is closely related to patterns of association and access to drugs.

In the period between initial enforcement of the Harrison Act and World War ii, most persons who became addicted to opiates through nonmedical channels probably did so either by virtue of close affiliation with another addict or in the course of thrill-seeking behavior (Dai 1937, p. 173). Following World War ii, however, a high proportion of those who became drug users had been introduced to the use of narcotics in the slum areas in which their families lived. These recent addicts have tended to come from family backgrounds and life circumstances conducive to the production of psychopathy. There is much evidence, however, that psychological difficulties are far more widespread than is illicit drug use. Recent research in New York City and Chicago suggests that the use of heroin and other opiates, in most instances, is learned through association with peers in the subculture of “street-corner society.” The norms of this subculture are generally inconsistent with and often openly hostile to those of conventional society. The orientation on the part of substantial numbers of adolescents is manifested in delinquency and in the search for and exploitation of “kicks” (Finestone 1957a).

In general, the prevailing sentiment toward drug use, even on the part of residents of slum areas, is decidedly negative. Most children learn that heroin and marijuana are considered “bad” by most adults. In areas of highest drug use, however, rejection of the standards of conventional society, distrust of policemen, and relatively favorable attitudes toward drugs tend to be much more widely prevalent, even among a cross section of school children, than in other areas of the city (Chein et al. 1964, p. 102). A substantial proportion of young people are likely to have friends or associates who use marijuana or heroin.

The subculture of addiction

Many young people have their initial drug experience with marijuana reefers provided by older companions. The neophyte who likes the experience and wishes to move toward regular use must have a more stable source of supply than can be provided by chance encounters with other users. He is likely to spend more time with persons who use marijuana and to avoid those who strongly disapprove (Becker [1953b] 1963, pp. 62–72). This reduces the need for secrecy in smoking marijuana and enhances the pleasures of use. Simultaneously, changing contacts help to negate the popular stereotype of the marijuana “addict.” It becomes apparent that marijuana does not completely transform the personality; the new user learns a series of positive beliefs about the beneficial effects of marijuana, beliefs constantly being reinforced by their verbalization within the group (Becker [1953b] 1963, pp. 72–78).

The use of heroin is a step further along the path of alienation from conventional values. Here the prevailing attitudes, even in delinquent subcultures, are much more negative. Here there is the promise of a bigger kick but also at much greater cost. Most of those who try heroin for the first time, however, are aware that addiction does not come from a single or an occasional trial. It is likely that few anticipate that they will be “hooked.” Some—no one knows what proportion— manage to use the drug for a time on an occasional basis and then stop altogether without ever becoming addicts (Chein 1964, p. 159). Others, especially those for whom heroin use leads to a marked increase in feelings of adequacy, move quickly to the subculture of the addict, where “connections” can be made and where the drug itself becomes the central fact of existence.

Lindesmith (1947, chapter 4) has noted the critical importance of the individual’s recognition that withdrawal sickness can be warded off by use of the drug. It is at this time that he becomes fully aware of the nature of addiction and of his dependency upon the opiates. Both his patterns of association and his self-image change markedly as he becomes assimilated into the subculture of addict society.

Social backgrounds, personality, and drug use

Certain personality characteristics of narcotics addicts are markedly different from those of normal middle-class persons, and to a lesser degree they are different from those of nonaddicted persons coming from the same social backgrounds as the addicts. One major expression of the personality differences is in attitude. Addicts are characterized by attitudes of pessimism and futility on the one hand and of distrust and rejection of the standards and representatives of middle-class society on the other. These attitudes do not merely characterize addicts, however. As indicated above, Chein found them to be rife among eighth-grade pupils in schools located in areas of high drug use. To a substantial degree, then, they would seem to be prevalent social orientations which are conducive to drug use.

Another major aspect of personality difference between the addict and the nonaddict is the low self-esteem and high degree of social immobilization of the narcotics user by virtue of anxiety. A major appeal of the opiates is that they permit the constricted ego greater scope and freedom (Chein 1964, chapter 9). But again the personality attributes appear to reflect aspects of the social environment in which the addict has been nurtured, particularly the devaluation and deprivation that are experienced by residents, especially minority group members, of urban slums. The same terms relating to personality characteristics have been used to describe slum dwellers elsewhere who were not involved in drug use (Clausen 1957, pp. 263–266). Within the areas of highest rates of drug use, users tend to come from families lacking a stable father figure, lacking warmth between parents, and characterized by vague or inconsistent standards (Chein 1964, chapter 10). All of these factors would tend to contribute to psychopathy in the child; families with such characteristics are in part a product of migration to and life in the urban slum.

The world of addiction

Criminality and drug use

Although narcotics use has long been prevalent in the underworld, prior to the passage of the Harrison Act the great majority of opiate users and addicts in the United States were law-abiding citizens. Thereafter, addiction or occasional use of opiates for nonmedical reasons could be maintained only by criminal means—either the illegal purchase of smuggled drugs or the theft of drugs. Moreover, few addicts could afford the high cost of illegal drugs without resorting to theft or other criminal activities.

In general, addiction to narcotics reduces the inclination toward aggressive or violent behavior (Joint Committee 1961, p. 68). In this respect, heroin is far less likely to lead to violence than is alcohol. It is the lack of the drug, rather than its consumption, that is most closely linked with criminal activities on the part of the addict. Larceny, or theft for money to buy drugs, is the dominant crime of the narcotics offender (Finestone 1957b, p. 71).

At the same time, drug use provides one type of adjustment within a delinquent milieu. Many, perhaps most, of the young drug users growing up in the worst urban slums are involved in delinquency long before they try marijuana or heroin. There is some evidence that those whose drug use is part of a subcultural pattern that begins with delinquency may be psychologically more sound than those whose delinquent behavior did not start until they had become drug users and needed money in order to support the habit (Chein 1964, chapter 6).

The important point to be made is that drug effects, even when harmful, are not the primary cause of criminal behavior. British opiate addicts are not criminals to any significant degree (Schur 1962, pp. 135–140). The meaning of drug use and its linkage with crime depends largely on the laws relating to narcotics and on public attitudes toward addiction.

Employment and drug use

To the extent that narcotics or other drugs become the central preoccupation of an individual, as is true of an addict, that individual is likely to be an undependable employee. A substantial proportion of physician addicts are reported to have functioned adequately for long periods while addicted to narcotics, but the great majority of addicts are, at best, irregularly employed (Schur 1962, p. 131). Except for entertainers and physicians, the population from which addicts are drawn in the United States tends to be relatively disadvantaged in the job market. Since possession of a drug calls for more serious penalties than do most forms of theft, there is little incentive for the active addict to work. Even in Britain, however, where addiction and drug possession are not denned as crimes, most addicts have unsatisfactory work records (Schur 1962, p. 134). It is not possible to state to what degree their poor work records reflect the personality problems that gave rise to their addiction or that are a direct consequence of the use of drugs.

Contextual supports

By virtue of his alienation from conventional norms and his stigmatization, the narcotics addict tends, even when he is not using drugs, to have his closest associations with persons who speak his argot and accept him without regard for his criminal record. Many addicts voluntarily undertake “cures” in one of the hospitals established to provide for drug withdrawal and treatment in a drug-free environment. Few appear to be content with continual addiction (Lindesmith 1947, chapter 6; Ray 1961, p. 134), but the rate of relapse to drug use is exceedingly high. Follow-up studies suggest that relapses tend to occur very soon after discharge from a treatment center. Of patients returned to New York City from the Public Health Service Hospital at Lexington, Kentucky, during the period from July 1952 to December 1955, only 9 per cent were voluntarily abstinent six months later and less than 3 per cent were abstinent for a full five years (Duvall et al. 1963). Yet at the end of the five-year period, nearly 25 per cent of the study group had been voluntarily abstinent for three months or more.

Ray (1961) notes that the abstinent former addict is likely to be viewed with distrust by relatives and representatives of conventional society. Even though not using drugs, he may be periodically picked up by the police for questioning. Under such circumstances, he is likely to turn again to his association with other addicts.

Narcotics control

The primary objective of efforts in the United States to control drug use has been to stamp out the trade in illicit drugs. Efforts to mobilize public sentiment against drug addicts and the drug traffic have often relied on the dissemination of markedly distorted information and on attempts to suppress consideration of alternative points of view (Eldridge 1962, pp. 39–40, 78–80). Legislation has provided severe penalties for the sale or possession of drugs, but this approach has neither eliminated illicit drug use nor contributed to the rehabilitation of addicts.

Most addicts engage in small-scale peddling of drugs on those occasions when they are able to purchase more than enough for their own needs. They are then subject to the same penalties for drug sale and possession as are the nonaddicted distributors of narcotics. As a consequence of longer prison sentences, the number and proportion of narcotics offenders, chiefly addicts, in prison populations has more than doubled. Increasingly, professional groups have called attention to the lack of success of punitive measures (Joint Committee 1961; Eldridge 1962; White House Conference 1963).

It is too soon to predict the effect of such re-evaluations, but attention has been focused on alternative approaches. One such approach is the so-called British system of control (Schur 1962). The basic legislation relating to narcotics use in England is not markedly different from that in the United States, except that penalties are far less stringent. Moreover, in interpretation of the law, the medical profession has been left free to deal with addiction as a medical problem. The addict has neither been stigmatized nor forced into criminal activity.

Hallucinogenic and other “new” drugs

In recent years a new group of drugs, the hallucinogens (also called psychedelic or psychotomi-metic drugs), has come increasingly into attention and use, especially among young intellectuals interested in deepening their psychic experiences (Barron et al. 1964). In the case of these drugs, as with alcohol, it appears that the effects are markedly influenced not only by the nature and amount of the drug taken but by the personality and current mood of the subject and by the context in which the drug is used and the expectations held. In a few places, cults have arisen around the use of the hallucinogens. Where this has occurred, some of the opprobrium directed toward illegal drug use has been noted.

More closely linked with the orientation toward thrill-seeking and deviant behavior that characterizes much opiate addiction in the United States has been the increasing use of amphetamine and other stimulants (White House Conference 1963, pp. 286–289). Although many of the new drugs are not addicting, their use is to a high degree expressive of rebellion and problematic behavior. It is not unlikely that experience with an ever-increasing number of new drugs will in time force a re-consideration of both the criteria and the standards underlying legislation for the control of drugs.

John A. Clausen

BIBLIOGRAPHY

Barron, Frank; Jarvik, M. E.; and Bunnell, S. 1964 The Hallucinogenic Drugs. Scientific American 210, April: 29–37. → A general review of effects and points of view regarding a new class of drugs.

Becker, Howard S. (1953a) 1963 Becoming a Marihuana User. Pages 41–58 in Howard S. Becker, Outsiders: Studies in the Sociology of Deviance. New York: Free Press.

Becker, Howard S. (1953b) 1963 Marihuana Use and Social Control. Pages 59–78 in Howard S. Becker, Outsiders: Studies in the Sociology of Deviance. New York: Free Press.

Chein, Isidor et al. 1964 The Road to H: Narcotics, Delinquency and Social Policy. New York: Basic Books. → Part I describes a comprehensive program of research on adolescent drug use.

Clausen, John A. 1957 Social Patterns, Personality, and Adolescent Drug Use. Pages 232–272 in Alexander H. Leighton et al. (editors), Explorations in Social Psychiatry. New York: Basic Books.

Dai, Bingham 1937 Opium Addiction in Chicago. Shanghai (China): Commercial Press.

Duvall, Henrietta J. et al. 1963 Followup Study of Narcotic Drug Addicts Five Years After Hospitalization. U.S. Public Health Service, Public Health Reports 78:185–193.

Eldridge, William B. 1962 Narcotics and the Law: A Critique of the American Experiment in Narcotic Drug Control. New York: American Bar Foundation. FINESTONE, HAROLD 1957a Cats, Kicks and Color. Social Problems 5:3–13.

Finestone, Harold1957b Narcotics and Criminality. Law and Contemporary Problems 22:69–85.

Joint Committee of the American Bar Association and the American Medical Association on Narcotic Drugs 1961 Drug Addiction: Crime or Disease? Bloomington: Indiana Univ. Press.

Kolb, Lawrence 1963 Factors That Have Influenced the Management and Treatment of Drug Addicts. Pages 23–33 in Symposium on the History of Narcotic Drug Addiction Problems: Proceedings. Edited by Robert B. Livingston. U.S. Public Health Service, Publication No. 1050. Washington: Government Printing Office.

Lewin, Louis (1924) 1931 Phantastica: Narcotic and Stimulating Drugs; Their Use and Abuse. New York: Dutton; London: Routledge. → First published in German. Reissued as Drugs: Their Use and Abuse in 1938.

Lindesmith, Alfred R. 1947 Opiate Addiction. Evanston, III.: Principia Press.

Lindesmith, Alfred R. 1965 The Addict and the Law. Bloomington: Indiana Univ. Press.

Narcotics. 1957 Law and Contemporary Problems 22: 3–154. → Contains review articles on various aspects of drug addiction in the United States.

Ray, Marsh B. 1961 The Cycle of Abstinence and Relapse Among Heroin Addicts. Social Problems 9:132–140.

Schur, Edwin M. 1962 Narcotic Addiction in Britain and America: The Impact of Public Policy. Bloomington: Indiana Univ. Press.

Sonnedecker, Glenn 1963 Emergence and Concept of the Problem of Addiction. Pages 14–22 in Symposium on the History of Narcotic Drug Addiction Problems: Proceedings. Edited by Robert B. Livingston. U.S. Public Health Service, Publication No. 1050. Washington: Government Printing Office. → A brief historical overview.

Terry, Charles E.; and Pellens, Mildred 1928 The Opium Problem. New York: Bureau of Social Hygiene. → The most comprehensive compilation of historical and scientific knowledge available up to 1928.

United Nations, Economic and Social Council, Com-mission on Narcotic DrugsSummary of the Annual Reports of Governments Relating to Opium and Other Dangerous Drugs. → Began publication with the 1944 Summary. Contains information relating to many aspects of narcotics production and abuse within member nations.

White House Conference on Narcotic and Drug Abuse 1963 Proceedings. Washington: Government Printing Office. → The Appendix, by an ad hoc panel on drug abuse, provides an excellent summary of the nature of drug use in the United States.

DRUGS

Drugs are notoriously difficult to define and yet present some of the most difficult ethical issues for the science and technology on which they are based. At the simplest level, drugs are molecules whose biochemical effects have been classified as socially desirable or undesirable in different times and places. Dorland's Medical Dictionary defines a drug as a "chemical compound that may be used on or administered to humans or animals as an aid in the diagnosis, treatment, or prevention of disease or other abnormal condition, for relief of pain or suffering, or to control or improve any physiologic or pathologic condition" (p. 510). But this ignores so-called recreational drugs, which may be described as substances used mainly for their psychoactive properties and pleasurable effects.

Historically drugs have been derived from plants and other natural materials and thus their production relied on indigeneous forms of knowledge and premodern techniques, often appropriated for modern applications. Over half of drugs in clinical use today continue to be derived from natural sources—including the excretions of insects, animal organisms, or microbes—from which they are extracted through direct or indirect processes (Aldridge 1998). The other half is synthesized through chemical processes that are now industrialized.

International Regulation

Ethical issues relating to human exploitation of indigenous knowledge and resources—sometimes called bio-prospecting—became central with the rise of a multinational pharmaceutical industry in the mid- to late-twentieth century. International treaties now provide safeguards that guarantee countries sovereign right over their genetic resources and a share of pharmaceutical profits derived from them. Yet such treaties also make national drug policy inflexible, inhibit innovation, and do not necessarily guarantee that indigenous groups that provide genetic materials are fairly compensated.

Given the high profit margins and relatively recession-proof nature of the pharmaceutical industry, drug production, marketing, distribution, and consumption are tightly regulated through a complex series of legal protocols and social controls that start from a set of international treaties that are coordinated through the United Nations Single Convention (1961), still the foundational document of international drug control (McAllister 2000). Prior to 1961 nine separate international treaties governed illicit or addictive drugs, primarily narcotics (opium and its derivatives), coca and its derivatives, and marijuana/hashish. The Single Convention defined the boundary between licit and illicit drugs, as well as legitimate medical and illegitimate, nonmedical, or recreational use, granting expert committees of the World Health Organization (WHO) authority for adding or altering drug schedules, which define how strictly drugs are regulated according to the level of their abuse liability. The Single Convention also mandated that national governments create and maintain drug-control agencies, and otherwise required signers to conform their domestic drug policies to its international mandate.

Regulation in the United States

Regulatory regimes are divided in the United States between illicit drugs, regulated by the Federal Bureau of Narcotics (FBN), the Treasury Department unit responsible for enforcing the Volstead Act (alcohol prohibition) and the Harrison Act, which transmuted into the Drug Enforcement Administration (DEA) in 1973; and licit drugs, regulated by the Food and Drug Administration (FDA) following the Food, Drug, and Cosmetic Act (1938). The 1938 Act granted the FDA authority to designate which drugs would be available only with a physician's prescription (Swann 1988). The liberalization of prescription laws in the 1960s and 1970s culminated in direct-to-consumer (DTC) advertising briefly becoming legal in the United States in the early 1980s prior to an FDA-imposed moratorium finally lifted in 1997. Supranational organizations such as the European Union have limited the spread of direct-to-consumer advertising (DTC) of prescription drugs. New Zealand is currently the only other country besides the United States that allows DTC, although it is under consideration elsewhere.

Well into the twentieth century, proprietary medicines were unregulated in terms of production, advertising, marketing, or distribution. Heavy advertising of commercial compounds emerged in the mid-nineteenth century United States, as patent medicine manufacturers were among the first to market their products nationally. Total advertising expenditures for proprietary medicines soon exceeded those of all other products combined; it was not unusual for nineteenth-century advertising budgets to exceed $100,000 per year, and some reached the million-dollar mark.

Narcotic drugs were restricted to prescription by the Harrison Act (1914), an outcome of growing international concern about widespread use and abuse of opiates, which were one of the few effective drugs then considered part of the medical armamentarium. An ongoing search for a non-addicting analgesic mounted by the National Research Committee propelled early-twentieth century innovation in the U.S. pharmaceutical industry in the context of concerns about addiction liability (Acker 2002). Addiction remains a classically public problem to which a coordinated federal response is understood as necessary, despite disagreement over the form that it should take. The United States remains the largest consumer of illicit drugs and has continued to struggle against what has proven a largely intractable problem. Basic research efforts into the neurobiochemistry of addiction led to the visualization of multiple opiate receptors, long hypothesized to exist, in the early 1970s. Federally funded studies of drug addiction have shifted away from the social and health consequences of abuse, and toward the use of molecular and animal models in establishing the basic neurobiological and now biogenetic mechanisms of drug action.

Drug Evaluation

Classified according to what is known about their mechanism of action, as well as their predominant effects on human and animal populations, both prescription and over-the-counter drugs must now be evaluated for safety, efficacy, abuse liability, and therapeutic effects. First their metabolic effects must be determined in animal models. Clinical trials in healthy human volunteers take place after pharmacokinetic studies in animals. Trials are divided into four phases, three of which take place before licensing and one of which occurs once patients are prescribed the drug by participating physicians. The large-scale clinical trials system in place in the United States since the 1960s is complex, lengthy, and expensive. Both the FDA and the National Institutes of Health (NIH) reluctantly became involved in regulating and coordinating the testing and licensure system for new drugs (Hertzman and Feltner 1997). Ethical concerns relevant to clinical trials include determinations of the capacity for informed consent of experimental human subjects; balancing rights to privacy and confidentiality with public access to information; the design and execution of double-blind, placebo-controlled studies; and how to go about occasionally halting a trial as adverse effects become clear.

Ethical questions are raised both in terms of the type of drug development, production, marketing, and distribution being promoted; and the conditions of use. Drugs play a different role depending upon whether they are administered within allopathic or homeopathic therapeutic regimes. Homeopathy involves the administration of minute dosages of drugs designed to produce symptoms in healthy persons that mimic the symptoms of the disease for which the person is being treated. Developed by Samuel Hahnemann (1755–1843), homeopathy has been the target of many conflicting claims concerning its safety and efficacy in the face of the dominant practice in western medicine, allopathic treatment, which seeks to produce conditions that are incompatible or antagonistic to the disease. Many aspects of complementary and alternative medicine (CAM) are now being explored through large-scale clinical trials, since tremendously high percentages of U.S. patients now seek alternative practitioners in conjunction with allopathic practitioners, leading to a vast and less regulated market for so-called nutraceuticals, off-label use of pharmaceutical drugs, and herbal remedies untested by scientific regimes.

One of the major events in twentieth century history of drugs was the coincidence between the trend toward deinstitutionalization of mental hospitals that began in the 1940s with the psychopharmacological revolution that occurred upon introduction of a major tranquilizer, chlorpromazine (CPZ, marketed as Thorazine in the United States and Largactil in Europe), in the 1950s. This was followed by the first popular use of pep pills (amphetamines) and the mass marketing of minor tranquilizers such as Miltown in the late 1950s, which brought advances in psychopharmacology to popular attention (Smith 1991). Since that time periodic concerns have surfaced as to the social value of drugs used for performance enhancement or marketed widely as lifestyle drugs in ways that have changed the meaning of medical use. Pfizer Pharmaceutical's introduction of Viagra, a drug used to temporarily correct erectile dysfunction and targeted toward relatively affluent male consumers, brought to light disparities in insurance coverage of lifestyle drugs such as the lack of insurance coverage for female contraceptives, whose coverage has been restricted due to the abortion controversy. This Viagra gap illustrates one of the persistently troubling ethical issues in the domain of drugs, namely that of research and development targeted toward developing or widening markets among the affluent through lifestyle or look-alike drugs that are simply a means for drug companies to gain market share, compared to the relative lack of attention to drugs for treating orphan diseases that seriously affect small numbers of individuals, or those diseases—such as malaria or schistosomiasis—that mainly affect individuals in the developing world.

While the FDA is often regarded as an agency that largely serves the needs of the pharmaceutical industry, three major reproductive health controversies of the 1960s and 1970s propelled the FDA into taking a somewhat proactive regulatory role. These were the development of hormonal methods of contraception; widespread prescription of Thalidomide to pregnant women in Europe, while the drug was still experimental in the United States when it was demonstrated to cause severe birth defects; and prescription of diethylstilbestrol (DES), which caused in utero defects and increased rates of cancer in the children of women who took it. These controversies arose simultaneously with interrelated social movements that targeted health and physician-patient relationships, including the patients' rights movement, the consumer rights movement, the women's health movement, and, later, the HIV/AIDS movement. These social movements sought to limit the use of certain classes of therapies such as electroshock (ECT) and drugs such as the major tranquilizers or benzodiazepines (Valium) among certain populations. They also agitated for increased inclusion in clinical trials, earlier and more democratic access to experimental drugs, and expanded patients' rights including privacy, confidentiality, and informed consent.

Pharmacogenomics

Pharmacogenomics is the attempt to identify individual, genetic variation in drug response—metabolism, transport, and receptors—and to extend those findings to population genetics through a variety of information and visualization technologies. Pharmacogenomics promises individually tailored medications that would likely decrease adverse drug reactions, currently the fourth leading cause of death in the United States.

Projects in this research arena raise novel ethical and legal issues related to the creation of sample repositories or banks of genetic materials that would enable hypothesis-driven research on statistically significant differences in the phenotypes of human subjects. Such research could help establish the safety, efficacy, and compatibility of certain classes of drugs for particular individuals or populations; and could be used to create a complex set of biomarkers that describe the particular complement of different neuroreceptors that an individual has that may make him or her more or less responsive to a range of addictive substances (tobacco, opiates, and others) or prescribed medications. Pharmacogenetic databanking is potentially useful for avoiding adverse consequences but could also create a rationale for genetic and health-related discrimination. As with previous advances in the field of pharmacology, pharmacogenetics presents a double-edged sword, and its meaning and ethical value will be determined by the social contexts in which it is deployed.

NANCY D. CAMPBELL

SEE ALSO Bioethics;Clinical Trials;Complementary and Alternative Medicine;DES (Diethylstilbestrol) Children;Food and Drug Regulatory Agencies;HIV/AIDS;Medical Ethics;Sports.

BIBLIOGRAPHY

Acker, Caroline. (2002). Creating the American Junkie: Addiction Research in the Classic Era of Narcotic Control. Baltimore, MD: Johns Hopkins University Press. Thorough historical study of addiction research up to the 1940s, including the ongoing search for a non-addicting analgesic.

Aldridge, Susan. (1998). Magic Molecules: How Drugs Work. Cambridge, England: Cambridge University Press. Highly accessible general introduction to drugs.

Balance, Robert, Janos Pogany, and Helmut Forstner. (1992). The World's Pharmaceutical Industries. Brookfield, VT: Edward Elgar.

Campbell, Nancy D. (2000). Using Women: Gender, Drug Policy, and Social Justice. New York: Routledge. Social and cultural history of the representation of different populations of women who have used illicit drugs in the twentieth-century United States.

Courtwright, David T. (2001). Dark Paradise: A History of Opiate Addiction in America, enlarged edition. Cambridge, MA: Harvard University Press. Classic historical demography on opiate addiction in the United States.

Cozzens, Susan E. (1989). Social Control and Multiple Discovery in Science: The Opiate Receptor Case. Albany: State University of New York Press.

Dorland's Medical Dictionary. 1980. Philadelphia: Saunders Press.

Healy, David. (2002). The Creation of Psychopharmacology. Cambridge, MA: Harvard University Press.

Hertzman, Marc, M.D., and Douglas E. R. Feltner, M.D. (1997). The Handbook of Psychopharmacology Trials: An Overview of Scientific, Political, and Ethical Concerns. New York: New York University Press.

Liebenau, Jonathan, Gregory J. Higby, and Elaine C. Stroud, eds. (1990). Pill Peddlers: Essays on the History of thePharmaceutical Industry. Madison, WI: American Institute of the History of Pharmacy.

McAllister, William B. (2000). Drug Diplomacy in the Twentieth Century. New York: Routledge. Detailed diplomatic history of the global regulation of drugs.

Musto, David F. (1999). The American Disease: Origins of Narcotic Control Policy, 3rd edition. New York: Oxford University Press. Foundational text in the field of drug policy history.

Smith, Mickey C. (1991). A Social History of the Minor Tranquilizers. New York: Haworth Press.

Swann, John P. (1988). Academic Scientists and the Pharmaceutical Industry: Cooperative Research in Twentieth-century America. Baltimore, MD: Johns Hopkins University Press.

Terry, Charles, and Mildred Pellens. (1970 [1928]). The Opium Problem. New York: Bureau of Social Hygiene. Reprinted by special arrangement with The American Social Health Association, Montclair, NJ: Patterson Smith. Fascinating compendium of over 4,000 nineteenth- and early twentieth-century studies on the effects of opiates.

White, William L. (1998). Slaying the Dragon: The History of Addiction Treatment and Recovery in America. Bloomington, IL: Lighthouse Institute. The best of very few historical works on drug treatment regimens.

DRUGS

From the Middle Ages, drugs referred to medicinal substances employed by chemists, pharmacists, and apothecaries. The word did not take on its modern associations with narcotics in particular until the mid-nineteenth century, with the increased recognition of opiate addiction. Once concepts and terminology evolved to address phenomena involving opiates, they transferred easily to substances such as cannabis and cocaine. Hallucinogens, however, were not widely acknowledged until the mid-twentieth century.

opiates

For centuries, opium (the congealed juice of poppy seed pods) was used in folk remedies and patent medicines to treat many common afflictions. It was cheaper than liquor, a fact often blamed for its popularity as a Saturday night recreation for English Midland factory hands and fenland farm workers in the 1830s and 1840s. As early as 1700, a few treatises on opium noted effects such as tolerance (the necessity for ever greater dosages to produce the original effect) and withdrawal (the onset of uncomfortable symptoms when dosages of the substance are decreased or halted), but these phenomena were little discussed until the mid-nineteenth century. Confessions of an English Opium-Eater (1821) by Thomas De Quincey (1785–1859) built upon a pattern hinted at in the 1816 poem "Kubla Khan" by Samuel Taylor Coleridge (1772–1834), establishing opium in the European popular imagination as both an exotic Oriental hallucinogen and the object of a shameful thralldom. Both writers also associated opium with visionary artistry, a connection cemented by other prominent artists who addressed opium in their works or were notorious users themselves, including English writers Percy Bysshe Shelley (1792–1822), Lord Byron (1788–1824), and Charles Dickens (1812–1870), American writer Edgar Allan Poe (1809–1849), French writer Charles Baudelaire (1821–1867), and French composer Hector Berlioz (1803–1869).

One reason opium's addictive tendencies went largely unremarked until midcentury was that raw opium is much less addictive than its alkaloid, morphine, which was first isolated in 1803 by the German pharmacist Friedrich Sertürner (1783–1841) and made popular throughout the developed world by the advent of the hypodermic syringe in the 1850s. By the 1870s, European medical professionals led by the Austrian Heinrich Obersteiner (1847–1922) and the German Eduard Levinstein (1831–1882) had defined a new disease known as "morphinism" or "morphinomania," characterized by a compulsion to use morphine. Linked closely to the treatment and legal control of alcoholism, the treatment of opiate addiction emerged as a new medical specialty.

Opium was also inextricably linked in the nineteenth-century with "the Orient," in part because popular traveler's tales often featured exotic Orientals eating or smoking opium, and the majority of the drug in European domestic use came from Turkey, Persia, and Egypt. Furthermore, the British East India Company's smuggling activities precipitated two so-called Opium Wars with China (1839–1842 and 1856–1860), prompting anti-opium crusaders to warn that Britain would someday suffer retribution. Such fears spread in the latter half of the nineteenth century. They figured prominently in published accounts of Oriental and English smokers in supposedly innumerable Chinese opium dens in London's East End, despite evidence that there were only a few modest establishments with any claim to the title at the time.

hashish

Oriental exoticism also pervaded the infamous Club des Haschischins, a group of Parisian intellectuals fascinated with the "Assassins" (Haschischins), legendary Islamic militants who reputedly smoked hashish (the resin secreted by flowers of the hemp plant) to see visions of paradise, be thereby inspired to murder their religious enemies, and so gain entrance to paradise. Members of the Club des Haschischins included Baudelaire, Gérard de Nerval (1808–1855), Alexandre Dumas (1802–1870), and Théophile Gautier (1811–1872). According to Gautier's 1846 account in Revue des Deux Mondes, members met in a secret Paris location where the drug was administered by an eminent doctor, often assumed to have been the psychologist Jacques-Joseph Moreau de Tours (1804–1884), who reported his self-experimentation with hashish in Du Haschisch et de l'Aliénation Mentale (1845; Hashish and mental illness). Baudelaire later recorded his own impressions of hashish and published them along with loosely translated excerpts from De Quincey's Confessions as Les paradis artificiels (1860; Artificial paradises). Gautier's and Baudelaire's descriptions of hashish were faintly echoed in Britain in a smattering of anonymous magazine articles and in the reference by Oscar Wilde (1854–1900) to an Oriental "green paste" associated with the title character's debauchery in The Picture of Dorian Gray (1891). Interest in the United States was evident in such publications as Fitz Hugh Ludlow's The Hasheesh Eater (1857) and H. H. Kane's subsequently famous "A Hashish-House in New York" in Harper's Monthly (1883).

cocaine

Workers in Peru, Bolivia, and Ecuador, where the coca plant grows wild, had long chewed coca leaves to limit fatigue and provide pleasure. The plant's potential was not widely noted in Europe, however, until the active alkaloid was isolated and named in 1860 by a graduate student, Albert Niemann (1834–1861), working with the chemistry professor Friedrich Wöhler (1800–1882) at the University of Göttingen. The same decade saw the advent of Vin Mariani, a Bordeaux wine steeped with coca leaves. First manufactured in 1863 by the French chemist Angelo Mariani (1832–1914), this coca wine became popular with drinkers throughout Europe, including Queen Victoria (r. 1837–1901) and Popes Leo XIII (r. 1878–1903) and Pius X (r. 1903–1914). It spawned imitations, most notably Coca-Cola, a preparation of coca leaves and cola nuts first marketed as a tonic in the United States in 1886. In 1883, German army physician Theodor Aschenbrandt published his findings that cocaine improved the endurance of soldiers. Sigmund Freud (1856–1939) read Aschenbrandt's article and experimented with cocaine on himself and others. He published a glowing account in 1884, making him one of the most visible representatives of a class of medical professionals who were initially enthusiastic about cocaine, as some others had been about morphine. As the danger of addiction and psychotic symptoms became clearer, however, recriminative counterarguments followed and Freud's professional reputation suffered.

See alsoAlcohol and Temperance; Baudelaire, Charles; Coleridge, Samuel Taylor; Decadence; Opium Wars; Popular and Elite Culture; Shelley, Percy Bysshe; Tobacco; Wilde, Oscar; Wine.

bibliography

Primary Sources

Jay, Mike, ed. Artificial Paradises: A Drugs Reader. London, 1999.

Secondary Sources

Berridge, Virginia, and Griffith Edwards. Opium and the People: Opiate Use in Nineteenth-Century England. London, 1981.

Davenport-Hines, R. P. T. Pursuit of Oblivion: A Global History of Narcotics, 1500–2000. London, 2001.

Lewin, Louis. Phantastica, Narcotic and Stimulating Drugs: Their Use and Abuse. Translated by P. H. A. Wirth. London, 1931.

Barry Milligan

Drugs

Since 8000 b.c.e. and the Aztecs' ceremonial use of peyote, drugs have played an integral role in the religious history of the Americas. However, hallucinogenic drugs assumed a more visible role in the United States after World War II. Drugs penetrated mainstream society in the 1960s as the psychedelic revolution, led by such proselytizers as Timothy Leary and Ken Kesey, became part of the large-scale restructuring of American religion. The political and cultural radicalism of this decade led to the questioning of institutional authority at all levels of society, including that of the mainline churches. As demand increased for alternative spiritualities and experiential insights, drugs provided many with a readily available shortcut to mystical enlightenment.

When consumed under the proper conditions, marijuana, mescaline, magic mushrooms (psilocybin), and their synthetic counterpart, lysergic acid diethylamide (LSD), catalyze emotional states of a deeply religious character; mediating feelings of unity with the universe, deep community with peers, synesthesia, transcendence of time and space, and insight into the social construction of reality. As hallucinogens became more readily available in the 1960s, they provided an outlet and a vehicle for various forms of religious, social, and political protest against a status quo, perceived by many at the time as inhibiting individualism and limiting personal freedom.

The religious character of the psychedelic movement may be gleaned from William James's study of mysticism in his The Varieties of Religious Experience (1902). James, a psychologist and philosopher, experimented with nitrous oxide and peyote in exploring alternative states of consciousness. His dabblings reflected his preference for religion that was an "acute fever" rather than a "dull habit." James's statement on the matter would later be held up by proponents of chemical mysticism: that "rational consciousness as we call it, is but one special type of consciousness, whilst all about it, parted from by the filmiest of screens, there lie potential forms of consciousness entirely different" (p. 388).

The assault on this screen began well before the 1960s, among musicians and writers outside the institutionalized religious sphere. Their experiments with various drugs were the historical precursors to the psychedelic movement. By the early 1920s, marijuana was already a popular drug among jazz musicians. In the 1940s, Beat writers Jack Kerouac, Allen Ginsberg, and William S. Burroughs were experimenting with marijuana and Benzedrine. In 1953 the English essayist and novelist Aldous Huxley ingested four-tenths of a gram of mescaline at his home in Hollywood, California. He believed the experience to be confirmation of the insights he had written about in his 1945 study of world mysticism, The Perennial Philosophy. He quickly published The Doors of Perception (1954), a description of his newfound spirituality and visions of "naked existence."

Only a month before Huxley's revelation, the U.S. government authorized Operation MK-ULTRA. The CIA's drug and mind control program was complemented by a large increase in scientific studies of the therapeutic use of hallucinogens in treating alcoholism, narcotics addiction, and juvenile delinquency. It was during this period of curiosity that clinical psychologist and Harvard lecturer Timothy Leary began his research into the religious dimensions of psychedelics. In 1962 Walter Pahnke, a graduate student in religion and society at Harvard and advisee of Leary, conducted his famous "Good Friday experiment." During a religious service at Marsh Chapel of Boston University, Pahnke assembled twenty divinity students and administered psilocybin to half of them while the other half received a placebo. Nine of ten of those who had taken psilocybin reported having an intense religious experience, while only one from the control group felt similar effects. Pahnke's results led Leary to conduct further experiments. After his expulsion from Harvard in 1963, Leary quickly set up a grass-roots, nonprofit group called the International Federation for Internal Freedom (IFIF) and began to preach the gospel of psychedelics from a New York estate called Millbrook.

Psychedelic seeds of religious change were also being sowed on the West Coast. In 1960 Ken Kesey, a graduate student in Stanford University's creative writing program, tried LSD as part of a federally funded research program. Enamored by his experience, Kesey soon published his first novel, One Flew over the Cuckoo's Nest, and used the royalties to gather a group of "Merry Pranksters" at his residence in La Honda, California. In 1964 they bought a 1939 International Harvester bus. They renamed it FURTHUR, painted it with Day-Glo colors, pasted a sign to the rear end that read "Caution: Weird Load," and then drove cross-country to New York. Their hijinks did more than anything else to popularize LSD among the youth of America. In 1965 Kesey and his followers began their series of "acid tests" in the San Francisco area, all-night LSD parties that included strobe lights, costumes, and music by the Grateful Dead.

The momentum of psychedelic culture laid the religious groundwork for the emergence of the counterculture in the late 1960s in and around the Haight-Ashbury district in San Francisco. Media coverage and the relatively new medium of FM radio gave voice to the psychedelic gospel. As social protest became fashionable, drugs became even more accessible and more inviting to thousands of youths, who thought their domestic situation in need of a spiritual boost. However, psychedelics soon became a form of recreation for the "Woodstock nation" rather than a means to religious enlightenment.

While the contemporary meaning of the psychedelic revolution remains a point of contention among scholars, there is no doubt that it marked a dramatic shift in American religious history. Despite the founding of various psychedelic churches such as the Church of the Awakening and the Neo-American Church, the legacy of psychedelica lies not in its institutionalization but in its legitimization of personal discovery and resistance. The experimental attitude of the counterculture affected the entire religious landscape of the United States and wrenched open an alternative space for religious belief and practice: increased interest in Eastern mysticism and literature; the growth of small religious groups and practices in the 1970s, including Hare Krishna and transcendental meditation; and the decreased liturgical hegemony of mainline churches. Most importantly, however, the widespread use of hallucinogens in the 1960s complemented the growing emphasis on individual experience in the religious life of Americans. Whether or not they had used drugs, Americans of all stripes began to re-emphasize individual experience in their religiosity. This trend would continue through the rest of the century.

See alsoNative American Church; New Age Spirituality; New Religious Movements; Peyote; Proselytizing; Psychologyof Religion; Religious Experience.

Bibliography

Braden, William. The Private Sea: LSD and the Search forGod. 1967.

Ellwood, Robert S. The Sixties Spiritual Awakening: American Religion Moving from Modern to Postmodern. 1994.

Farrell, James J. The Spirit of The Sixties: The Making ofPostwar Radicalism. 1997.

Huxley, Aldous. The Doors of Perception. 1954.

James, William. The Varieties of Religious Experience. 1902.

Leary, Timothy. High Priest. 1968.

Lee, Martin A., and Bruce Shlain. Acid Dreams: TheComplete Social History of LSD: The CIA, the Sixties, andBeyond. 1985.

Solomon, David, ed. LSD: The Consciousness-ExpandingDrug. 1964.

Wolfe, Tom. The Electric Kool-Aid Acid Test. 1969.

John Lardas

DRUGS

Drugs are articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans or animals, and any articles other than food intended to affect the mental or body function of humans or animals.

Gonzales v. Raich

In a closely watched case involving the reach of federal authority, the U.S. Supreme Court in June 2005 reversed a decision of the U.S. Court of Appeals for the Ninth Circuit, ruling that the federal government was within its constitutional power to outlaw the use of marijuana, even when a state has legalized possession of the drug for medicinal purposes. The decision invalidated statutes in nine states that had legalized marijuana for such purposes.

California enacted the Compassionate Use Act of 1996, Cal. Health & Safety Code §11362.5 (West 2005), which allowed citizens of the state to obtain and use marijuana for medical purposes. Under the statute , those patients who

obtained and used marijuana for approved medical uses were not subject to criminal prosecution or sanction. About 100,000 chronically ill people in California have used cannabis for medicinal reasons.

Angel McClary Raich has suffered from debilitating illnesses for most of her life. She developed scoliosis as a teenager and wore a back brace. She was later diagnosed with endometriosis. After she became a mother during her twenties, she developed wasting syndrome and, eventually, a brain tumor. She became paralyzed on one side of her body and was confined to a wheelchair. Doctors were unable to prescribe medication that would alleviate her pain. About a year after California passed its statute, a nurse recommended that Raich try marijuana therapy. The therapy worked so well that Raich no longer used a wheelchair. Caregivers provided the marijuana to Raich at no charge.

In a similar case, Diane Monson suffers from a degenerative back disorder. She began taking marijuana in 1998 at the suggestion of a doctor. She has stated that, without the drug, the pain caused by her back condition would be unbearable. Monson grows her own marijuana.

Federal agents from the Drug Enforcement Administration raided Monson's home and seized six marijuana plants in 2002. Fearing future raids, the women brought suit in the U.S. District Court for the Northern District of California. They sought declaratory and injunctive relief, asking the court to prevent the federal government from prosecuting possession and use of medical cannabis.

In seizing the marijuana, the federal government acted pursuant to the Controlled Substances Act, 21 U.S.C. §802 (2000). The statute does not recognize any legitimate medical use for marijuana. The plaintiffs' primary argument was that Congress had exceeded its authority under the Commerce Clause in regulating purely intrastate, non-commercial activities, such as the growth, possession, and use of marijuana for purely medical purposes.

The plaintiffs' argument appeared to be bolstered by two U.S. Supreme Court decisions of the past decade. In United States v. Lopez, 514 U.S. 549 (1995), the Court held that Congress did not have the authority under the Commerce Clause to render possession of a weapon near a school zone a federal offense. Similarly, in United States v. Morrison, 529 U.S. 598 (2000), the Court held that Congress did not have the authority to provide a civil remedy under the Violence Against Women Act. In both of these cases, the Court concluded that the federal government was not regulating economic activity that substantially affected interstate commerce.

The district court, after a lengthy review of Morrison and Lopez, ruled against the plaintiffs. According to U.S. District Judge Martin J. Jenkins, "In the final analysis, neither Lopez nor Morrison answer definitively the question posed to this Court: whether the Controlled Substances Act, as applied in this case, is beyond the purview of Congress' power to regulate activity under the Commerce Clause. Therefore, the Court is still bound by existing Ninth Circuit authority on this issue." Because the Ninth Circuit had previously upheld the constitutionality of the Controlled Substances Act, the district court denied the plaintiffs' motion. Raich v. Ashcroft, 248 F. Supp. 2d 918 (N.D. Cal. 2003).

The plaintiffs appealed the decision to a panel of the Ninth Circuit. Although the court, per Judge Harry Pregerson, recognized that the circuit had upheld the Controlled Substances Act in the past, this case presented different circumstances. Unlike decisions involving drug trafficking, Raich's and Monson's case involved intrastate, non-commercial cultivation of marijuana, which was used according to state law and with the advice of a doctor. The court reviewed the decision in light of four factors identified in Morrison relating to the effect of the regulated activity on interstate commerce. After reviewing the case in light of these factors, the court found that the Controlled Substances Act was likely unconstitutional as applied in that case. Raich v. Ashcroft, 352 F.3d 1222 (9th Cir. 2003).

The federal government, through then- Attorney General John Ashcroft, filed a petition for a writ of certiorari with the U.S. Supreme Court on April 20, 2004. The Court granted the petition on June 28. It heard oral arguments in the case on November 29. The case garnered attention as much because of its focus on the power of the federal government as its focus on whether marijuana may be used legally for medicinal purposes. "There are questions about the authority of the federal government and the states' authority to determine what medical practice is," said Marc Spindelman, a law professor at Ohio State University. "There are questions about what the purpose of the Controlled Substances Act is. And there are questions about Congress' authority to regulate commerce when it involves controversial medical decisions, and what tools, if any, the federal government should use in the national debate about how medical practice should or shouldn't evolve."

By a 6-3 vote, the Supreme Court reversed the Ninth Circuit decision. In an opinion by Justice John Paul Stevens, the Court noted that the federal government may regulate purely local activities that are part of an economic "class of activities" that have a substantial effect on interstate commerce. According to the Court, the production of marijuana has a substantial effect on the national supply and demand of the product. The Court concluded that Congress had a rational basis for determining that marijuana production and possession substantially affect interstate commerce and thus held that it is within Congress's power to regulate this activity. In reaching its conclusion, the majority noted that the Ninth Circuit had read Lopez and Morrison too broadly. Accordingly, it reversed the Ninth Circuit decision. Gonzales v. Raich, __ U.S. __, 125 S. Ct. 2195, __ L. Ed. 2d __ (2005).