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LaGuardia Committee Report on Marihuana
A careful testing of the motor and sensory functions of the nervous system was included in the general physical examination of each subject. Of motor functions, reflex activity and muscular response and coordination were determined; of sensory functions, perception of touch, pain and temperature stimuli; of specialized functions, taste, hearing and vision. In the eye, the corneal and light reflexes were tested and a retinal examination was made. In this neurological examination no pathological conditions were found in any of the subjects.
In the psychiatric examination attention was paid to general intelligence and knowledge in relation to the subject's background, to relevancy of talk in conversation, to orientation as to time, place and situation, to memory of past and recent events, to ability in simple arithmetic, to judgment in reaching decisions, and to the presence of abnormal mental content shown by delusions, hallucinations, obsessions, and ideas of persecution. There was no evidence of disordered cerebral functioning in any of the group.
As would be expected, differences in grades of intelligence and in orderliness in thinking and reasoning were noticeable. The Bellevue Adult Intelligence Test was administered to a total of 60 male subjects, 40 marihuana users and 20 nonusers. The average I.Q. for the user group was 96.7, range 70 to 124, and for the non-user group the average I.Q. was 104.5, range 93 to 114. Both groups may therefore be classified as of average intelligence.
When analyzed according to racial distribution the two groups were even better equated intellectually than the total results indicate. For the 28 white subjects examined (13 users and 15 non-users) the average I.Q. for the users was 106.1 range 77 to 124, and for the non-users the average I.Q. was 106.3, range 96 to 114. There were 24 Negro subjects, 19 users and 5 non-users. The average I.Q. for the users was 92.6, range 70 to 112, while for the non-users the average I.Q. was 98.8, range 93 to 101. Although 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. In any event, the disparity in results would not be considered significant.. The average I.Q. of the 2 Puerto Rican users was 91.0, range 72 to 100.
Reports on mental deterioration due to toxic, organic or psychotic factors as given in the literature reveal that in such cases the individual scores on the Bellevue Adult Intelligence Test show marked irregularity, depending upon the functions involved in the deteriorative process. As a group, the marihuana users tested in this study showed very even functioning, and what little irregularity occurred can be explained on the basis of language and racial factors.
The physical and psychiatric examinations were of a qualitative rather than a quantitative nature. In the special examinations and tests of organ and system function, quantitative measurements were obtained for 17 marihuana users. These subjects were selected for the reason that they had smoked marihuana for the longest period of time. The figures for years of usage and number of cigarettes smoked daily were taken from each subject's statement.
Marihuana users accustomed to daily smoking for a period of from two and a half to sixteen years showed no abnormal system functioning which would differentiate them from the non-users.
There is definite evidence in this study that the marihuana users were not inferior in intelligence to the general population and that they had suffered no mental or physical deterioration as a result of their use of the drug. Addiction and Tolerance
A drug addiction is characterized by a compelling urge to use the drug for the prevention or relief of distressing mental and physical disturbances which occur when the necessary dose is delayed or omitted. A drug habit is also characterized by an urge to use the drug, but this is not compelling. The abstinence symptoms, which are expressions of nervous states, are not particularly distressing and do not occur as long as the person's attention is placed on other matters.
Drug tolerance in the narrower sense used here means that larger doses than those originally used are required to bring about the effects desired by the subject. In the case of morphine, tolerance develops because of addiction, but in other instances tolerance may be present without addiction and addiction without tolerance. When both are present the matter takes on greater importance because of the extremes to which the addict goes to obtain the drug constantly and in increasing quantities.
As our group of subjects included 48 users of marihuana, opportunity was afforded for some conclusions concerning marihuana addiction and tolerance. Practically all of our group of users stated that they could and often did voluntarily stop the smoking for a time without any undue disturbance from the deprivation. In the sociologic study reported by Dr. Schoenfeld it was found that smokers had no compelling urge for marihuana. If "reefers" were not readily available there was no special effort made to obtain them from known sources of supply. Dr. Walter Bromberg, Psychiatrist-in-Charge, Psychiatric Clinic, Court of General Sessions in New York, states: "The fact that offenders brought up on marihuana charges do not request medical treatment on their incarceration (with its cessation of drug supply) argues for the absence of with drawal symptoms.''(1) From interviews with several hundred marihuana users he concludes that true addiction was absent.
(1) Bromberg, W. "Marihuana: a psychiatric study." J.A.MA. 113:4, 1939.=20
The evidence submitted here warrants the conclusion that as far as New York City is concerned true addiction to marihuana does not occur.
The evidence concerning acquired tolerance is less clear-cut Tolerance develops during the periods when the drug is being taken and accounts for the necessity of increasing the dosage to bring about the desired effects. How long the tolerance persists after the drug administration is stopped has not been definitely established in any instance.
The statements of marihuana usage and time since stoppage given by eight of our subjects are summarized in Table 26. (TABLE 26)
On one or more of the numerous occasions on which marihuana was administered each of these subjects received what was considered a minimal effective dose. One (J.B.) was given 1 cc., another (A.B.) 3 cc., the others 2 cc. In all instances the customary physical effects, conjunctival injection, dilated and sluggishly reacting pupils, tremors and ataxia, were observed. With these doses the subjects also experienced the sensation described as "high." The only conclusion warranted here is that if acquired tolerance does occur it persists for a limited period only.
Further evidence, though indirect, was brought out by Dr. Shoenfeld's investigation and by personal interviews with our 48 users. There is agreement in the statements that among users the smoking of one or two cigarettes is sufficient to bring on the effect known as "high." When this state is reached the user will not continue smoking for fear of becoming "too high." When the desired effects have passed off and the smoker has "come down," smoking one cigarette brings the "high" effect on again. This could not be the case had a steadily increasing tolerance developed.
The evidence available then=AD-the absence of any compelling urge to use the drug, the absence of any distressing abstinence symptoms, the statements that no increase in dosage is required to repeat the desired effect in users-=ADjustifies the conclusion that neither true addiction nor tolerance is found in marihuana users. The continuation and the frequency of usage of marihuana, as in the case of many other habit-forming substances, depend on the easily controlled desires for its pleasurable effects. Possible Therapeutic Applications
If a drug has well-marked pharmacological actions and low toxicity, as appears to be the case with marihuana, a consideration of special interest is its possible therapeutic application. In the older clinical literature marihuana was recommended for use in a wide variety of disorders, but in recent years it has almost disappeared from the materia medica and it was dropped from the United States Pharmacopeia twenty years ago.
In view of the laboratory and clinical findings obtained in this study the question of the therapeutic possibilities of the drug was considered. Marihuana possesses two qualities which suggest that it might have useful actions in man. The first is the typical euphoria- producing action which might be applicable in the treatment of various types of mental depression- the second is the rather unique property which results in the stimulation of appetite. In the light of this evidence and in view of the fact that there is a lack of any substantial indication of dependence on the drug, it was reasoned that marihuana might be useful in alleviating the withdrawal symptoms in drug addicts.
At the Riker's Island Penitentiary observations were made on 56 inmates who were addicted to morphine or heroin. Two groups were selected, the addicts in each being matched with those in the other group as to age, physical condition, duration and intensity of habit, and number of previous attempts at cure. The subjects in one group received no treatment or were given Magendie's solution according to the usual hospital regimen while those in the other group were treated with 15 mg. of tetrahydrocannabinol three times daily with or without placebo (subcutaneous water injection). An attempt was made to evaluate the severity of the withdrawal signs and symptoms. The impression was gained that those who received tetrahydrocannabinol had less severe withdrawal symptoms and left the hospital at the end of the treatment period in better condition than those who received no treatment or who were treated with Magendie's solution. The ones in the former group maintained their appetite and in some cases actually gained weight during the withdrawal period.
Since psychological factors play a large part in the withdrawal symptoms of at least a certain proportion of morphine addicts, there are grounds for the assumption that a drug having the properties of marihuana might be of aid in alleviating mental distress during the withdrawal period. However, the studies here described were not sufficiently complete to establish the value of such treatment, and before conclusions can be drawn the problem must be investigated under completely controlled conditions. PHARMACOLOGICAL STUDY (1) S. Loewe, MD (2) (1) From the Department of Pharrnacology, CorneU University Medical College. (2) Part of the experimental work here reported was conducted in collaboration with W. Modell SUMMARY
1. This review of the pharmacology of marihuana is centered around the chemical and pharmacological identification of the active principles of hemp. Coordination of chemical and pharmacological investigations as a prerequisite to success in the search for unknown principles and of the analysis of the structure-activity relationship of these compounds is discussed.
2. In a survey of the sources of preparations with marihuana activity, hemp seeds are disclosed as a heretofore unknown source of active substances.
3. Varieties of hemp can be distinguished according to genotypic differences of the content of active principles which persist over generations independently of soil and climate.
4. The pharmacological actions of marihuana are analyzed with regard to their specificity and their usefulness as indicators of specific components.
5. Sixty-five substances from the new class of cannabinols and related classes are reviewed, among which are the essential components of the marihuana-active hemp oils. The discovery of this class, the synthesis of these representatives, and their structural elucidation led the way to the discovery of the active substances.
6. Quantitative assay procedures are described for the most important marihuana effects that are observed in the animal experiment. The assay of the ataxia effect in the dog and of the synergistic hypnotic effect in the mouse with refined procedures are shown to be reliable expedients for measuring these two marihuana actions, whereas the areflexia effect in rabbits failed to show the reproducibility required for quantitative purposes.
7. With the aid of these methods the natural tetrahydrocannabinols are shown to be active principles responsible for ataxia in dogs and psychic action in man. They are intermediate products between the two ineffective substances which compose the bulk of hemp oil: a labile excretion product of the plant, cannabidiol, and a stable end- product, cannabinol. The conversion of cannabidol into active tetrahydrocannabinol by a natural environmental influence has been paralleled by ultraviolet irradiation in vitro.
8. Numerous isomers, homologs and analogs of tetra- and hexahydrocannabinol are shown to possess the specific marihuana action. The potency varies enormously and is highest in natural, optically active=ADlaevogyrous=ADtetrahydrocannabinols.
9. The significance of many of the structural details of the tetrahydrocannabinol molecule for marihuana activity is elucidated by quantitative determinations of relative potency. Special attention was devoted to a study of the importance of variations in the length of the 3- alkyl side chain of tetrahydrocannabinols. In studying methyl to nonyl homologs of the original amyl derivative occurring in nature, it was found that the maximum potency is not at the amyl, but at the hexyl homolog, and in two out of four homologous series at the representatives with still longer side chains.
10. In addition to the ataxia and the psychic action, other pharmacological attributes of the tetrahydrocannabinols are a decrease in the respiratory and an increase in the pulse rates in the non-narcotized dog.
11. The synergistic hypnotic action of marihuana in the mouse is to be attributed to the otherwise inert cannabidiol.
12. The corneal areflexia action in the rabbit was much stronger in impure distillate oils than in pure tetrahydrocan nabinols, which leads to the conclusion that this action is either poorly reproducible or must be attributed to a different, as yet unknown, principle.
13. Only one among the numerous cannabinol derivatives, 7- methyltetrahydrocannabinol, was found to produce a motor stimulant=AD-convulsant=AD-action concomitant with ataxia action. A cannabidiol derivative, tetrahydrocannabidiol, was found to have specific convulsant action in the dog.
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