Samuel Allentuck, MD

The functions of the body organs and systems were studied in the manner common to hospital practice according to the methods and with the equipment in use at Welfare Hospital. The study was designed to show not only the effects of varying doses of marihuana but also whether subjects who had long been users of the drug gave evidence of organic damage. The tests were made before the drug was administered, during its action, and often in the after period.

The heart and circulation, blood composition, kidney, liver and gastro-intestinal function, and basal metabolism received special consideration. The results of the study follow

The Circulation

Pulse Rate
Coincident with the onset of marijuana symptoms, there usually occurred a rise in pulse rate. The peak was reached in one and one-half to three and one-half hours. The maximum increase was from thirty to forty beats per minute in most instances but in some it was from fifty to sixty beats. The decline after the peak was at times sharp, at other times gradual. The rise and its extent appeared to be dependent upon the mental state induced by the drug, that is, it was greater in states of euphoria and talkativeness, laughter, and body movement. As these symptoms subsided the pulse rate fell correspondingly.

Blood Pressure
Blood pressure changes were variable. In general, there was a rise in blood pressure coincident with the increase in pulse rate. There was no consistency in this, however. Thus, in one instance, with an increase of thirty beats per minute in pulse rate, the blood pressure rose 20 mm. Hg.; in another, with a rise in pulse rate of fifty beats per minute, the blood pressure remained unchanged. The diastolic pressure in general followed the systolic. There was no consistent relationship between the degree of change and the size of dosage.

Circulation Time
In a number of instances, ether and saccharin were injected into the antecubital vein and the time intervals required for the recognition of ether in the expired air and of the taste of saccharin were measured. The measurements made before and during marijuana action showed no differences and it was concluded that marijuana has no effect on the arm to lung and arm to tongue circulation time.

Electrocardiograms
Electrocardiographic records were made of all subjects before the administration of marijuana and during the drug action. The dose ranged from 1 cc. upwards, going as high as 17 cc. for one subject. In a number of instances a preliminary dose was given in the morning and a second, usually much larger, later, the record being taken after the second dosage. The readings and interpretations were made by Dr. Robert C. Batterman.

In eleven of the subjects abnormal electrocardiograms were noted. A description of these follows:

A.B. Control    P split in leads 2 and 3.
Marijuana    same
T.E.    Control    P split in leads 2 and 3. Left axis deviation.
Marijuana    same throughout
C.H. Control    T diphasic in leads 1 and 2.
Marijuana T diphasic in leads 2, 3 and 4.
J.H.    Control    Normal PR interval .19
A.B. Control    P split in leads 2 and 3.
Marijuana    same
T.E.    Control    P split in leads 2 and 3. Left axis deviation.
Marijuana    same throughout
C.H. Control    T diphasic in leads 1 and 2.
Marijuana T diphasic in leads 2, 3 and 4.
J.H. Control    Normal PR interval .18
Marijuana P split in leads 1, 2 and 3. PR interval .22
W.J. Control    Elevated ST segment, lead 1 and 4. P split
in leads 1, 2 and 3. T diphasic in 3. P diphasic in lead 4.
Marijuana LA deviation. P split in leads 1, 2 and 3.
T inverted in lead 3.
J.P.    Control    P split in leads 1, 2 and 3. Diphasic in lead
4. T split in 2, diphasic in 3.
Marijuana P split in 2.
J.R.    Control    RA deviation, P split in lead 1.
Marijuana RA deviation, P split in leads 1 and 2.
C.S.    Control    Deep Q in lead 3. Inverted T in lead 3.
Depressed ST segment lead 2.
Marijuana    same throughout
L.V. Control    Ventricular rate 120. RA deviation. P split
in leads 1, 2, 3, and 4. PR interval .20 Marijuana Ventricular rate 120. No deviation. P split in leads 1, 2, 3, and 4. PR interval .24.
B.W. Control    Normal
Marijuana Sinus tachycardia. T inverted in leads 3 and 4.
H.W. Control    T split in leads 1, 2 and 3. P inverted in
lead 3. Wassermann positive.
Marijuana    same throughout

In nine of the subjects, seven users and two non-users, abnormal electrocardiograms were noted in both the readings taken before and those taken after the administration of marijuana. In four of these the tracings resemble the pattern of those seen in patients with rheumatic heart disease, but it is impossible to state what underlying pathological conditions were present in the group as a whole. In two users the control records were normal, the marijuana ones abnormal.
In six subjects not included in the list given, a sinus tachycardia, and in two a sinus bradycardia were seen after the ingestion of marijuana.
In all the remaining subjects no abnormalities were seen before or during marijuana action.

Hematology

Blood morphology and certain chemical constituents of the blood were studied before and during marijuana action, on sixty-one subjects, the dosage ranging from 2 to 21 cc. Before the administration of marijuana the hemoglobin reading was between 80 and 90 percent in thirty-six subjects and over 90 percent in twenty-two; during marijuana action it was from 80 to 90 in nineteen subjects and over 90 percent in thirty-nine. Three showed a low hemoglobin percentage before, 65, 70 and 77 percent, but a rise to 79, 90, and 95 percent during the drug action.

The blood counts showed the usual individual variations but the average counts for the sixty-one subjects were: before the administration of the drug, red blood cells 4,800,000 and white blood cells 8,900; during the drug action, 4,900,000 and 9,500 respectively.

The urea nitrogen, calcium and phosphorus blood concentration figures are given in Table 4.

From these blood studies it is seen that marijuana in the range of dosage stated produced no appreciable change in hemoglobin or cell count or in blood urea, calcium, and phosphorus. The blood examinations were made at varying periods during the subjects' stay at the hospital and in all instances marijuana had been given previously on a number of occasions. Thus, one subject had been given a total of 85 cc., another 143 cc., and a third 169 cc. The results show, therefore, that in addition to the lack of effect from a single dose, there was no cumulative effect from previous doses.

Blood sugar determinations were made on sixty-two subjects, forty-two users and twenty non-users. The blood samples for all tests were taken in the morning before breakfast. In the case of the tests made during marijuana action, the drug was administered two or three hours before the samples were taken.

The incidence of rise, fall, or no change in the blood sugar after the ingestion of marijuana is shown in Table 5, and the blood sugar changes in relation to dosage are shown in Figure 1.

For thirty-eight subjects twenty-seven users and eleven non-users, the differences between the control and marijuana figures were within plus and minus 10 mg. percent. In five, four users and one non-user, there was a rise of from 11 to 14 mg. percent, in fourteen a rise of 15 mg. percent or more, and in five a fall of 15 mg. percent or more. The blood sugar figures for subjects showing a rise or fall of 15 mg. percent or more are given in Table 6.

            
From these tables it is seen that while there was a trend toward a rise in blood sugar levels during marijuana action, for the majority of the subjects there was no significant change from the control levels. In the instances where a rise or fall of 15 mg. percent or more occurred, a level of over 100 mg. percent was noted in only five subjects under marijuana; in the fourteen others the range kept between 70 and 100 mg. percent, which may be considered normal limits. Throughout there was no distinction between users and non-users in regard to blood sugar levels.

The Kidney

Routine examinations of twenty-four-hour urine specimens were made on all subjects for periods before and following marijuana administration. In no instance were albumin, sugar, casts, blood cells or other abnormal elements found.

Thirty-six subjects were given 1,000 cc. of water and the urine was collected for three one-hour periods. The procedure was repeated after the administration of marijuana in doses varying from 2 to 13 cc. An analysis of the figures obtained gave no evidence of a diuretic or antidiuretic effect from marijuana.

It was observed that an urge to urinate was a not infrequent occurrence during marijuana action. Since this was not accompanied by any appreciable increase in the amount of urine output, it is probable that it was a psychological reaction.

The phenolsulfonphthalein test for kidney function was carried out on forty-nine subjects before and during marijuana action. The dose ranged from 4 to 17 cc. The results are shown in Table 7.

There was a decrease of 2.5 percent in the total amount excreted by the forty-nine subjects after the administration of marijuana as compared with the amount excreted under normal conditions. This difference is well within the limits of technical error.
The results of the examinations showed therefore that the administration of marijuana brought about no structural or functional change in the kidney as determined by the techniques employed.

The Liver

No clinical evidence of liver damage was observed in any of the subjects before or after marijuana had been administered. The bromsulfalein test was given to a number of the subjects. The dye was injected in amounts of between 2 and 3 mg. for each kilogram of weight and the blood examined after thirty minutes. In twenty instances where marijuana was given in dosages ranging from 2 to 10 cc. and in one instance where 20 cc. was administered, the dye was absent from the blood after the thirty-minute interval.

The Gastro-Intestinal Tract

As has been stated, a characteristic effect of marijuana is a sensation of hunger and an increased appetite. Disagreeable effects which may occur are nausea and vomiting. The frequency with which the symptoms were noted is given in Table 8.

         
As shown in the table, after the ingestion or smoking of marijuana more than half the subjects experienced hunger and increased appetites. A desire for sweets was especially strong, and users believe that the taking of candy or sweetened drinks lessens the "too high" effect which may follow marijuana smoking. The tendency toward a rise in blood sugar after the ingestion of marijuana indicates some need of the tissues for more sugar, but there is no explanation of the mechanisms involved.

While nausea and vomiting might be attributed to irritant effects of marijuana, on the other hand these symptoms occurred after smoking and in one instance after an intramuscular injection of tetrahydrocannabinol. The action here is presumably a central one.

The effects of marijuana on gastric motility and secretion were studied by Dr. Louis Gitzelter. A Miller-Abbott balloon attached to a Levine tube was passed into the stomach through one nostril and a Levine tube alone through the other nostril. The balloon was inflated with air to a pressure of approximately 10 mm. of water and connected with a tambour which registered gastric contractions on a kymograph. The other Levine tube was used to withdraw gastric contents at stated periods.

With the subjects in a fasting state, control records of gastric motility and measurements and analysis of gastric secretion were made throughout a period of an hour or more. The procedure was repeated on subsequent days following the administration of marijuana (6, 8, 6, 15, and 15 cc.) and at a time when the subjects were in a "high" state. A comparison of the two sets of findings gave no evidence that marijuana had any effect on motility or brought about any change in gastric secretion.

Roentgenograms, which were taken of the stomach of one of the subjects after a barium test meal, showed the emptying time of the stomach to be three hours both before and after the administration of marijuana. In another subject there was considerable delay in the emptying time during the marijuana action.

The Brain

Brain Metabolism

The effect of marijuana on the metabolic rate of the brain was investigated by studying the oxygen and carbon dioxide content of the arterial and venous blood drawn from the carotid artery and the internal jugular vein. The blood samples were obtained as simultaneously as possible, collected under mineral oil, and kept under anaerobic conditions until analyzed. Coagulation was prevented by the use of oxalate, and glycosis was inhibited by the addition of fluoride. The blood samples were analyzed for oxygen and carbon dioxide by the method of Van Slyke and Neil.

For analyses made when the subjects were under the influence of marijuana, the blood samples were collected two and a half or three hours after the drug was given, at a time when the subjects were in a state classed as "high."

The results presented in Table 9 show no consistent change in the metabolism of brain tissue as measured by blood oxygen and carbon dioxide concentration in four subjects showing clinical evidences of marijuana intoxication. Circumstances prevented an extension of the study.

Electroenchephalograms

Electroencephalographic records of fifteen subjects were made by Dr. Hans Strauss. There appeared to be a relationship between the typical euphoric reaction produced by marijuana and an associated increase in the alpha activity seen in the electroencephalogram. However, similar increase of alpha activity was observed in two subjects who received no marijuana. It is known that a high degree of alpha activity is suggestive of relaxation or perhaps the shutting off of any disturbing extraneous environmental stimuli and these findings merely suggest that marijuana is conducive to mental relaxation in some individuals.

Basal Metabolism

The basal metabolic rates of sixty-one subjects were determined before and during marijuana action. The Sanborn apparatus was used and the determinations were made in the morning before breakfast. The marijuana dosage ranged from 2 to as high as 20 cc. In the group of sixty-one subjects, forty-five were classed as users, sixteen as non-users. The accompanying table gives the data on forty-three subjects whose metabolic rates were within a range of +9 to -13 percent, both under normal conditions and while under the influence of marijuana. Of these, nineteen showed a rise in basal metabolic rate of 2 to 12 percent, twenty-three a fall of 2 to 13 percent, and in one the rate did not change.

The remaining eighteen subjects had a basal metabolic rate of plus or minus 15 percent or more either before or after marijuana was administered. Of these, there was a rise in fourteen and a fall in four following the ingestion of marijuana, but in only four of these subjects was the rise significant, the rates being +30, +32, +18, and +25, after doses of 20, 2, 8, and 6 cc. respectively. The figures for this group are shown in Table 11.   

         
The control figures are lower than those commonly reported. Of the sixty-one subjects, the rate in eleven was on the plus side, in thirty-eight on the minus side within a range of +9 and -15 percent, while for four it was O. In eight the rate was between -16 and -23 percent. It is possible that prison life is conducive to a lowering of metabolic processes but our study is too limited to allow any generalization.

From the figures shown, it may be concluded that in the majority of subjects, marijuana caused no appreciable change in metabolic rate, although in those having an initially low rate, there was usually a rise. What changes occurred had no relationship to marijuana dosage, and there was no distinction between users and non-users.

Vital Capacity

Along with the determination of the basal metabolic rate, the measurement of vital capacity was made on sixty-six subjects before and after marijuana was administered. There was a decrease in forty-one, an increase in eleven, and no change in fourteen. Such changes as occurred were insignificant. The average vital capacity during the control period was 3.6 liters (range 2.3-5.1); after marijuana 3.5 liters (range 2.1-4.9).

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SUMMARY

The most consistent effect of marihuana observed in this division of the study was an increase in pulse rate which began shortly after the taking of the drug, reached a peak in about two hours, and gradually disappeared. In-a few instances a temporary sinus tachycardia or sinus bradycardia was noted, but except for these there were no abnormalities in rhythm. The increase in pulse rate was usually accompanied by a rise in blood pressure.

There was in general an increase in the blood sugar level and in the basal metabolic rate, quite marked in some subjects, but in the majority the levels reached did not exceed the high normal limits.

An increase in the frequency of urination was often observed.

There was, however, no appreciable increase in the total amount of urine passed during the drug action.

Hunger and an increase in appetite, particularly for sweets, was noted in the majority of the subjects, and the taking of candy or sweetened drinks brought down a "too high" effect of the drug.

Nausea and vomiting occurred in a number of instances, diarrhea only during psychotic episodes.

On the other hand, the blood showed no changes in cell count, hemoglobin per cent, or the urea nitrogen, calcium and phosphorus figures. The figures for the circulation rate and vital capacity and the results of the phenolsulfonphthalein test for kidney infection and the bromsulfalein test for liver function were not different from those of the control period. The electrocardiograms showed no abnormalties which could be attributed to a direct action on the heart. In the few observations on gastric motility and secretion no evidence of marihuana action on these functions was obtained.

The positive results observed, increase in pulse rate and blood pressure, increase in blood sugar and metabolic rate, urge to urinate, increased appetite, nausea and vomiting, and diarrhea, were not intensified by an increase in dosage, for they could occur in an equal degree after the administration of any of the effective doses within the range used. All the effects described are known to be expressions of forms of cerebral excitation, the impulses from this being transmitted through the autonomic system. The alterations in the functions of the organs studied come from the effects of the drug on the central nervous system and are proportional to these effects. A direct action on the organs themselves was not seen.