PLAN AND SCOPE

Interest in the effects of marihuana on the human subject follows two main lines: first, concerning what may be called pleasurable effects which account for its widespread use- and second, regarding undesirable effects, including those leading to criminal and other antisocial acts.

In his monograph on marihuana, Walton has reviewed at length the literature on hashish experience. He has grouped these descriptions as retrospective accounts by professional writers and physicians who have taken the drug through curiosity or scientific interest, reports by physicians concerning patients who have taken excessive doses, and observations by psychiatrists on subjects under marihuana influence. In all of these instances a dose toxic to the individual had been taken and the effects described correspond to psychotic episodes of greater or less degree.

In the literature there are commonly described two basic types of effect, one of excitation, psychic exaltation, and inner joyousness, with divorcement from the external world; the other a state of anxiety with fear of consequences, such as death or insanity. Either one of these types of reaction may be experienced alone, but usually both are present during the intoxication. They occur in no regular sequence but replace each other in rapid succession. The euphoric and anxiety states are generally accompanied by mental confusion, a rapid flow of dissociated ideas, and a feeling of prolongation of time and spatial distortion. Sexual desires or phantasies may also occur.

The detailed descriptions of the experience vary. Those given by trained writers, such as Ludlow and Bayard Taylor, are vivid and dramatic, embodying sensual, visual, and auditory illusions-phantasies of overpowering splendor and beauty, on the one hand, and intense suffering and horror on the other. The authors, familiar with stories of hashish effects and gifted with strong imaginative powers, undoubtedly were expectant of much that happened. The account given by the eminent Philadelphia physician, H. C. Wood, while following the same general pattern, has much less embellishment. He describes a feeling of well-being and inner joyousness and buoyancy and the performance of antics which he knew to be foolish but was unable to control. He was able to recall no illusions or hallucinations. Later a state of anxiety came on, developing into an overpowering fear of death.

A number of studies by psychiatrists on selected subjects have been reported. An excellent example is that of Kant and Krapf. Each acted as subject for the other and the effects of marihuana are described and analyzed at length. In general, the objective in such studies is the interpretation of the reactions in terms of disturbances in psychological processes and functionings. The descriptions referred to have been given by persons of a higher social class, well educated and accustomed by training to act in conformity with conventional social behavior. Although a state of irritability may occur and threats of suicide be made by individuals of this type under toxic doses of marihuana, it is noteworthy that in none of the descriptions is there found an expression of antagonism or antisocial behavior which led to acts of violence or what would be called criminal conduct.

Of more direct interest are the publications of Walter Bromberg, psychiatrist, Bellevue Hospital, Psychiatrist-in-Charge, Psychiatric Clinic, Court of General Sessions of New York County. Marihuana users who are brought before the court or admitted to the hospital come under his observation and he has reported at length on the psychiatric observations of 29 of these who showed psychotic reactions. He describes two types of reactions, one an acute marihuana intoxication with a psychotic syndrome, the other a toxic psychosis. Acute intoxication occurs in any individual if the marihuana is taken in sufficiently large doses. It comes on promptly and passes off some hours later. In marihuana psychosis, the symptoms are much more severe and of longer duration. He describes a number of cases in which the psychotic state continued for a number of days and required hospitalization.

The toxic psychosis seen in marihuana users occurs at any time and is of indefinite duration. Bromberg states that the relationship between cannabis and the onset of a functional psychotic state is not always clear. The personality factor is of undoubted importance and other toxic agents, such as alcohol and other drugs, as well as endogenous elements, may be involved. The symptoms, except for the longer duration, resemble those observed in persons under marihuana intoxication, but often take on the characteristics seen in schizophrenic or manic- depressive psychosis.

A description of 11 cases admitted to Bellevue Hospital is given for illustration. The marihuana was taken in the form of cigarettes. In this group were 5 Negroes, 2 of whom were women, 1 Puerto Rican, and 5 whites, one of whom was a Mexican and another a boy of 16. Except for one of the whites, a homosexual, they were all of a low intellectual and social order. One of the Negroes was arrested for following women in Central Park. The others were admitted at their own request, or were sent in by the police or family. Three of the group had definite sexual stimulation but in none was there an outburst in the form of an attack on women. The Puerto Rican became confused and excited and began chasing people with an ice pick. Shortly after his discharge he was readmitted to the hospital, was diagnosed as definitely psychotic, and was transferred to a state hospital as a schizophrenic. The majority of the group, 8 in fact, had psychopathic personalities and 3 of these were transferred to state institutions for further care. The group as a whole is representative of those who come into the hands of the police because of abnormal conduct and who are the source of the sensational newspaper and magazine stories.

Bromberg's findings concerning the lack of a positive relationship between marihuana and crime are described in the sociological section of this study.

In marihuana literature, the action of the drug is usually described from retrospective observation of the effects on a single individual. Relationship to varying dosage, to the subject's personality and background, to environmental conditions when the drug was taken, is given little if any attention. It is the lack of information concerning these and other factors involved in marihuana reaction which has given rise to the present confusion regarding its effects.

The clinical study here described was designed to afford information not found in marihuana literature but necessary for any comprehensive view of marihuana action. For obtaining this information there were these requisites: an adequate number of subjects for the study, a clear understanding of the mental and physical make-up of each subject, a uniformity of environmental factors, accurately graded dosage of marihuana, and standardized methods of obtaining and recording marihuana effects. In addition to defining the usual and unusual effects of marihuana, as shown by subjective and objective symptoms and alterations in behavior and in physical reaction, the study was expected to answer questions which must arise in consideration of the problem as a whole. Of special importance are these: Do marihuana users show fundamental traits differentiating them from non-users? Do users present evidence of psychological or physical damage directly attributable to the drug? What are the pleasurable effects which account for the widespread usage of marihuana? To what extent does it lead to antisocial or dangerous behavior?

The sections covering the clinical study are under the following headings:

A. Medical Aspects

1. Symptoms and Behavior

2. Organic and Systemic Functions

B. Psychological Aspects

1. Psychophysical and Other Functions

2. Intellectual Functioning

3. Emotional Reactions and General Personality Structure

4. Family and Community Ideologies

C. Comparison Between Users and Non-Users from the Standpoint of Mental and Physical Deterioration

D. Addiction and Tolerance

E. Possible Therapeutic Applications

Organization for the Study

The clinical studies were carried out at the Welfare Hospital (1) a New York City hospital for chronic diseases on Welfare Island. The quarters assigned to the study consisted of a ward of eight beds for the group to be studied at any one period, an adjoining ward of two beds for the study of individuals of the group, three additional rooms with equipment for special examinations, and a diet kitchen for the preparation of the subjects' meals.

Four female nurses were employed and the subjects in the larger ward were under constant supervision. In addition to routine records, each nurse reported the behavior of the subjects while she was on duty. Guards were assigned from the Department of Correction and the New York City Police Force for the subjects drawn from the Riker's and Hart Island penitentiaries and the House of Detention for Women.

The facilities of the Third Medical Division laboratory were used for general clinical laboratory examinations and for more detailed study of organ functioning. For measurement of psychological reactions, special apparatus was provided. A description of equipment used for each division of the study is given under its proper section.

Subjects Selected for the Study

For the purpose of establishing a uniform plan of procedure to be followed throughout the study, a test group of 5 individuals who had had no previous experience with marihuana was selected. These were volunteers who were paid for their services. They were of a low socio-economic level, but classified as of better than average intelligence. Only one of the group came within the range of what is considered normal personality. They represented the type of person who would readily take to marihuana were the opportunity offered.

The main group, 72 subjects, was drawn from the inmates of the penitentiaries at Riker's and Hart Islands and the House of Detention for Women, all of which are under the supervision of the Department of Correction of New York City. There were two advantages in selecting subjects from this particular group; first, they could be kept under continuous observation throughout the period desired, and second, they constituted an excellent sample of the class in New York City from which the marihuana user comes. The subjects all volunteered for the study after having its purpose and the part they were to take in it fully explained to them.

Race, Sex and Age.

Of the group, 65 were males and 7 were females; 35 were white, 26 were Negroes, and 11 were Puerto Ricans. The ages ranged from 21 to 37 years except for one who was 45 and another who was 43. Of the women, 6 had been opium addicts for a number of years.

Previous Experience with Marihuana.

Forty-eight of the group, including 6 of the women, gave a history of marihuana smoking. The extent of the usage was variable- for some it was occasional, while others had indulged in the habit fairly steadily over a period of years. Of the 48 users, those who were sellers of marihuana were probably the most consistent smokers, as in carrying on the traffic they would endeavor to keep a stock on hand. But in any instance, the number of cigarettes smoked during any stated period would vary according to circumstance. Thus one user stated that he smoked from 2 to 6 marihuana cigarettes a day, another from 10 to 15 a day, another 3 or 4 a week, and another 5 or 6 a month. Those who smoked daily are here classified as steady users, those who smoked when opportunity was offered but not daily, as occasional users.

(TABLE 1)

The users had all been deprived of marihuana from the time of their arrest, the shortest period being two weeks, the longest, one year and ten months. They all stated that the habit had often been interrupted voluntarily and the enforced discontinuation of it had caused no discomfort.

Health Record.

The subjects were individually selected by Dr. Allentuck as suitable for the study. A physical and neurological examination at the hospital showed no evidence of disease. However, the Wassermann and Kline tests gave positive results for 6 subjects and the Kline test alone was positive for 2 and doubtful for 2. These figures are consistent with those of the population from which the group was selected. Of the 12,000 inmates of the Riker's Island Penitentiary in 1940 and the 8,000 in 1941, 10 per cent reacted positively to serological tests.

Intelligence Record.

Sixty subjects (40 users and 20 nonusers ) to whom the Bellevue Adult Intelligence Test was given had an average I.Q. of 99.3, range 70 to 124. The average I.Q. of the user group was 96.7, range 70 to 124, while that for the non-user group was 104.5, range 93 to 114.

When analyzed according to racial distribution, the two groups were even better equated intellectually than the total results indicate. Of the 28 white subjects examined, the average I.Q. of the 13 users was 106.1, range 77 to 124, and that of the 15 non-users was 106.3, range 96 to 114. The 19 Negro users had an average I.Q. of 92.6, range 70 to 112, and the 5 Negro non-users averaged 98.8, range 93 to 101. Although in the colored group the non-users averaged 6.2 points higher than the users, it must be taken into account that the number of Negro non-users tested was small. The average I.Q. of the 8 Puerto Rican users was 91.0, range 72 to 100; that is, they were very similar in mental ability to the Negro users. From the results obtained from the Bellevue Adult Intelligence Test, one may conclude that neither the users nor the nonusers were inferior in intelligence to the general population.

Marihuana Used

The marihuana that was used for oral administration was supplied by Dr. H. J. Wollner, Consulting Chemist of the United States Treasury Department. It was in the form of an alcohol fluid concentrate, the alcohol content ranging from 55 to 67.3 per cent and the content of solids from 22.9 to 33.6 Sm. per 100 cc.

According to the bio-assay made by Dr. S. Loewe of the Department of Pharmacology of the Cornell University Medical School, the strength of the fluid concentrate was found to be from 71 to 90 per cent of that of the U.S.P. fluid extract for cannabis marketed by Parke, Davis and Company. The fluid extract was not miscible with water and had a characteristic, disagreeable taste which made it easily recognized. For these reasons the concentrate was evaporated to a viscid consistency and made into pill form, with glycyrrhiza as the excipient. Each pill was equivalent to 1 cc. of the concentrate.

For controls, glycyrrhiza pills without marihuana were used. Several products prepared by Dr. Roger Adams in his investigation of the chemistry of marihuana were used. A comparison of their action with that of the concentrate will be found below. In addition to the concentrate, marihuana cigarettes were used. These were obtained from supplies confiscated by the New York City Police. Each contained approximately from .4 to .8 gm. of marihuana. As the quality of the marihuana varied and the amount of active principles taken in with the smoke was unknown, there was no exactness in dosage. In general, however, it appeared that smoking 2 cigarettes was equivalent to taking 1 pill.

The minimal dose of the concentrate which produced clearcut effects was 2 cc. During the repeated observations on each member of the group larger doses were given, commonly up to around 8 cc. and in one instance up to 22 cc. For smoking, from one to as many as eleven cigarettes were used.

The Active Principles.

Determination of relative potencies of drugs having similar action can be made on human beings to a limited extent only. The comparison is based on easily measurable effects on some organ or system on which the drug has a highly selective action, but the existing state of the system influences greatly the ensuing result.

Marihuana effects come mainly from action on the central nervous system. The type and degree of response of this system to stimuli of various origins vary in different individuals and in the same individual at different times. When marihuana is given the pre-existing state cannot be classified but it has influence in determining the response, and the same dose of marihuana does not produce identical effects in different subjects or in one subject at different times. In general, however, when the dose given is definitely effective the responses are of a fairly uniform character.

For this reason the relative potency of the active principles supplied by Dr. Roger Adams could be determined only approximately. The principles used were the natural tetrahydrocannabinol, the synthetic isomer, and the synthetic hexylhydrocannabinol. These all brought on effects similar to those of the marihuana concentrate. The estimate of their relative potency is as follows: 1 cc. of the concentrate, representing the extraction from 1 Gm, of marihuana, had as its equivalent 15 mg. of the natural tetrahydrocannabinol, 60 mg. of the synthetic hexylhydrocannabinol, and 120 mg. of the synthetic tetra compound. In explaining the differences in the estimated potencies, the rates of absorption must be taken into account since the action of marihuana depends on the amount of active principle absorbed and its concentration in the brain at a certain time.

The main conclusion is that the action of the marihuana concentrate is dependent on its tetrahydrocannabinol content and that the synthetic compounds retain the action of the natural principle.

Procedure

The procedure for examining the main group of subjects was adopted in the light of the experience gained from the preliminary study.

The subjects were brought to the hospital in groups of from six to ten, and they stayed there from four to six weeks. Each subject had his history taken and was given a physical neurological, and psychiatric examination on the day of admission.

Since it has been shown that pulse variation is the most constant index of marihuana action, the pulse rate was recorded every half hour during the day with the subjects at rest for five minutes before each reading.

During the following days, through careful observation by the Director, the general make-up of the subject, his personality, the character of his responsiveness, and his behavior in new surroundings were determined both before and while he was under the influence of marihuana. Additional information came through the nurses' reports.

In addition, each subject was given a series of tests before and after the administration of marihuana in order that the changes brought about by the drug might be measured. Included among these tests were psychological tests for mental functioning and emotional reactions, psychomotor tests for both simple and complex psychophysical functions, tests to determine such abilities as musical aptitude and the perception of time and space, and laboratory examinations to test the functioning of the various organs and systems of the body.