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)

Table 1: Previous experience with marihuana of 40 subjects
Years of Use	Number of Steady Users	Number of Occasional Users
1-5	13	4
6-10	16	4
over 10	9	2
----	----	----
Total	38	10

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.

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