The widespread publicity describing the dangerous effects of marihuana usage in New Orleans and other Southern cities, especially among school children, had its repercussion in the city of New York, and some anxiety was experienced as to the possibility that similar conditions were present or might develop here. Because of this, Mayor LaGuardia asked The New York Academy of Medicine for an opinion as to the advisability of studying the whole marihuana problem. The Academy recommended that such a study be made and outlined its scope in general terms. Following this, the Mayor appointed a committee empowered to make the study. This committee consisted of two internists, three psychiatrists, two pharmacologists, and one public health expert, and the Commissioners of Correction, of Health, and of Hospitals, and the Director of the Division of Psychiatry of the Department of Hospitals, ex officio.

The Committee formulated a plan for the study, and the expenses were arranged for through grants by the New York Foundation, the Friedsam Foundation and the Commonwealth Fund. The study was begun in April 1940.

The first phase of the study concerned the extent of marihuana smoking in New York City, its incidence among school children, its relation to crime, and its effects on individuals using it. For obtaining this information, the Commissioner of Police assigned to the Committee six police officers, four men and two women, Who served as "plain clothes" investigators. These investigators circulated in the districts in which marihuana appeared to be most widely used, particularly Harlem, associated with marihuana users, and found out as much as possible about sources of supply, means of distribution, and effects of marihuana on users. Included in this survey were a careful watch on school children in both grade and high schools and interviews with school principals.

As a result of this investigation the Committee came to the conclusion that marihuana distribution and usage is found mainly in Harlem, the population of which is predominantly Negro and Latin-American, and to a less extent in the Broadway area extending from 42nd to 59th Streets. The local supply comes from individual peddlers and from "tea-pads," which are establishments for marihuana smoking. There are no figures available as to the number of marihuana users in New York City, but a conservative estimate is that there are some 500 peddlers and 500 "tea-pads" in Harlem.

The marihuana users with whom contact was made in this study were persons without steady employment. The majority fall in the age group of 20 to 30 years. Idle and lacking initiative, they suffer boredom and seek distraction. Smoking is indulged in for the sake of conviviality and sociability and because it affords a temporary feeling of adequacy in meeting disturbing situations.

The confirmed user smokes from 6 to 10 cigarettes a day. The effects are easily recognized by the smoker, the desirable stage being what is known as "high." When this is reached, the smoking is stopped. If a "too high" state is reached, the taking of beverages such as beer or sweet soda pop, or a cold bath are considered effective countermeasures.

In most instances, the behavior of the smoker is of a friendly, sociable character. Aggressiveness and belligerency are not commonly seen, and those showing such traits are not allowed to remain in "tea-pads."

The marihuana user does not come from the hardened criminal class and there was found no direct relationship between the commission of crimes of violence and marihuana. "Tea-pads" have no direct association with houses of prostitution, and marihuana itself has no specific stimulant effect in regard to sexual desires.

There is no organized traffic in marihuana among New York City school children, and any smoking that occurs in this group is limited to isolated instances.

Smoking marihuana can be stopped abruptly with no resulting mental or physical distress comparable to that of morphine withdrawal in morphine addicts.

The second division of the study was the clinical one, the purpose of which was to ascertain the effects of marihuana on the individual user. There were two phases of this work, the general medical study and the psychological study. Wards in the municipal hospital on Welfare Island (now known as Goldwater Memorial Hospital) were made available by the Commissioner of Hospitals. The subjects for the study were drawn from the prison population at the Penitentiary on Riker's Island, as arranged by the Commissioner of Correction. They were under sentence for terms varying from three months to three years, most of them for what would be called minor criminal offenses. They volunteered for the study, the purpose and procedure of which had been fully explained to them. They were kept in the hospital in groups of 6 to 10, for a period of study of approximately a month. The subjects afforded the sample especially desired, for over half of them were marihuana smokers and the others of the class from which marihuana smokers come. The personnel conducting the study consisted of a physician in charge, with an assistant physician, three psychologists, and a secretary. The subjects were under the constant supervision of the medical staff, nurses and attendants.

In studying the effects of marihuana on the 77 subjects selected for the study, the drug was given either in the form of an extract taken by mouth, or was smoked in cigarettes. The dose given to produce definite systemic reactions ranged from a minimal one to 1 cc. to a maximum of 22 cc. of the extract, and from 1 to 10 cigarettes. The effects of smoking appeared immediately and usually passed off in from one to three or four hours. Those from the extract came on more gradually and persisted for a longer time, in some instances for twenty-four hours or more. As the dose for any individual was increased, the effects usually were more marked and of longer duration, but the effect of any given dose varied with the individual subjects.

Although some of the subjects became restless and talkative under marihuana influence, a mental state characterized by a sense of well-being, relaxation and unawareness of surroundings, followed by drowiness, was present in most instances when the subject was left undisturbed. Generally, there was observed a difficulty in focusing and sustaining mental attention. In company, the subjects were lively and given to talkativeness, fits of laughter and good-natured joking. The pleasurable effects, classed as euphoric, were frequently interrupted or replaced by a state of apprehension of varying degree.

In a limited number of the subjects there were alterations in behavior giving rise to antisocial expression. This was shown by unconventional acts not permitted in public, anxiety reactions, opposition and antagonism, and eroticism. Effects such as these would be considered conducive to acts of violence. However, any tendency toward violence was expressed verbally and not by physical actions, and in no case was restraint by force needed.

In addition to its effect on mental states, physical symptoms resulting from the administration of marihuana were recorded. Of these, tremor, ataxia, dizziness, a sensation of floating in space, dilation of the pupils, dryness of the throat, nausea and vomiting, an urge to urinate, hunger, and a desire for sweets were the most striking. Tremor and ataxia and dizziness were of the greatest frequency. These symptoms may be disturbing to the subject, and if marked enough, cause anxiety and interrupt the euphoric state.

On some occasions, instead of the marihuana concentrate, preparations supplied by Dr. Roger Adams were given. These were tetrahydrocannabinol, made from cannabidiol, corresponding to a principle found in the plant, a synthetic tetrahydrocannabinol, an isomer of the natural one, and a synthetic hexyl-hydrocannabinol. They all produced effects similar in character to those from the concentrate. Their relative potency could be determined only approximately. The rough estimate was that 1 cc. of the concentrate had as its equivalent 15 mg. of the natural tetrahydrocannabinol, 60 mg. of the hexylhydrocannabinol, and 120 mg. of the synthetic tetrahydrocannabinol.

In the total group studied, what are known as psychotic episodes occurred in 9 of the subjects. In 6 instances, they were of short duration, persisting for from three to ten hours, and were characterized by mental confusion and excitement of a delirious nature with periods of laughter and of anxiety. These effects correspond to those often reported in marihuana literature and are examples of acute marihuana intoxication, which in many ways is similar to acute alcoholic intoxication. In the other 3 cases, one subject had a mild psychotic reaction after smoking one cigarette. Later, a typical psychotic state came on four hours after the subject had taken tetrahydrocannabinol and persisted for six days. This subject subsequently was found to have a history of epileptic attacks so that the psychotic episode was probably related to epilepsy. The second subject had previously been a drug addict. She was given marihuana on several occasions, at times showing only euphoric effects and other times confusion and worriment. She left the hospital depressed and moody, and a week later was committed to a state hospital with the diagnosis of psychosis. After six months, she was discharged as cured. The third subject showed no unusual effects of marihuana which was given on several occasions during his stay at the hospital. Some days after his return to the penitentiary he developed a psychotic state diagnosed "Psychosis with psychopathic personality." This was considered an example of what is known as "prison psychosis," a condition which has been noted in persons emotionally unstable subjected to the depressing atmosphere of prison incarceration. The precise role of marihuana in the psychotic states in the three unstable subjects is not clear. In the case of the second and third subject, the fact that they were sent back to prison to complete their sentences must be considered an important if not the main factor in bringing on the psychosis.

In the clinical study of the effect of marihuana on functions of various organs of the body, there were found an increase in pulse rate and blood pressure and an increase in blood sugar and metabolic rate. No changes were found in the circulation rate and vital capacity. Tests on renal and liver function were negative. No changes were found in blood counts and hemoglobin, or blood nitrogen, calcium and phosphorus concentrations. The electrocardiogram showed no abnormalties which could be attributed to direct action on the heart, and from a few observations made, marihuana appeared to be without effect on gastric motility and secretion. The positive results found, as well as the occurrence of nausea and vomiting, an increase in the frequency of urination, and the sensation of hunger and an increase in appetite, may be considered results of central nervous excitation, producing peripheral effects through the autonomic nervous system.

The psychological study, planned and carried out by experienced psychologists, was concomitant with the general medical one and was devoted to determining the effects of marihuana on psychomotor responses and certain special abilities, on intellectual functioning, and on emotional reactions and personality structure.

For psYthomotor effects, procedures were followed which gave records affording quantitative measurement. Static equilibrium and hand steadiness were the functions most strongly affected by marihuana. The body swaying was general in direction and not greater in one axis than in others. These effects came on during the first hour after the extract was given, reached a peak in about four hours, and persisted for some eight hours. After smoking, the effects came on much sooner—within a few minutes—and were of shorter duration, about three hours. Complex hand and foot reactions showed impairment, but simple reaction time, the strength of grip, speed of tapping, auditory acuity and musical ability, and estimation of short time intervals and small linear distances were unchanged. The findings in the women correspond to those in the male subjects. In both groups there was marked individual variability, irrespective of dosage.

It was found that marihuana in an effective dose impairs intellectual functioning in general. Included under this heading are adverse effects on speed and accuracy in performance, on the application of acquired knowledge, on carrying out routine tasks, on memory, and on capacity for learning.

Marihuana does not change the basic personality structure of the individual. It lessens inhibition and this brings out what is latent in his thoughts and emotions but it does not evoke responses which would otherwise be totally alien to him. It induces a feeling of self-confidence, but this expressed in thought rather than in performance. There is, in fact, evidence of a diminution in physical activity. While suggestibility may be increased by small doses, larger ones tend to induce a negativistic attitude.

From the study as a whole, it is concluded that marihuana is not a drug of addiction, comparable to morphine, and that if tolerance is acquired, this is of a very limited degree. Furthermore, those who have been smoking marihuana for a period of years showed no mental or physical deterioration which may be attributed to the drug.

The lessening of inhibitions and repression, the euphoric state, the feeling of adequacy, the freer expression of thoughts and ideas, and the increase in appetite for food brought about by marihuana suggest therapeutic possibilities. From limited observations on addicts undergoing morphine withdrawal and on certain types of psychopathic disturbances, the impression was gained that marihuana had beneficial effects, but much more extensive and controlled study is required for definite conclusions to be drawn concerning therapeutic usage. It should be borne in mind that the effects of marihuana, more than in the case of other drugs, are quite variable ih different individuals and in the same one at different times.

The chapter on the pharmacology of marihuana, prepared by Dr. Loewe, reviews the results of collaborative work of three laboratories (The Pharmacological Laboratory at the Cornell Medical College, the William Albert Noyes Laboratory at the University of Illinois, and the Laboratory of the Bureau of Narcotics at Washington, D. C.) which led to the discovery of the active principles, the elucidation of their origin, and the assembling of data on the relationship between chemical structure and biological activity. The chapter is introduced by a survey of the geographical distribution and botanical relationships of plants with marihuana activity.

The principles involved in bioassay are discussed and a method for marihuana assay described. The synthetic tetrahydrocannabinol of Adams was taken as the standard of reference and the characteristic reaction of ataxia in dogs measured quantitatively for the degree of activity. By this method the potency of samples and preparations of marihuana and of natural and synthetic principles has been determined and relationships between chemical structure and pharmacological activity elucidated.

The main components which have been isolated from marihuana oil containing the active principles are cannabidiol, cannabinol and isomeric tetrahydrocannabinols. The first two, but not the last, have been obtained as crystalline substances. The chemical structure and synthesis of these compounds have been described by Adams.

The typical effects of marihuana on man are ascribed to actions on the central nervous system. In dogs, the characteristic effect is ataxia. A delayed increase in pulse rate, a decrease in respiratory rate and blood pressure, and retching and vomiting were also observed. These effects are produced by tetrahydrocannabinol but not by cannabinol or cannabidiol. A derivative of the latter, tetrahydrocannabidiol, after a latent period of from thirty to seventy minutes following intravenous injection, had a specific convulsant action on the dog.

In rabbits a characteristic effect of marihuana extracts is corneal areflexia. This is also not produced by cannabidiol or cannabinol but does occur after tetrahydrocannabinol. However, impure oil mixtures have this action to a greater extent, from which it is suggested that a third unknown principle is present in the plant.

Cannabidiol has a synergistic hypnotic action with pernoston in mice. Neither cannabinol nor the synthetic tetrahydrocannabidiols had this effect.

The ataxia action of marihuana was considerably increased by a central stimulant, benzedrine.

No evidence was found of an acquired tolerance for the drug.

In examination of the data presented in the detailed clinical study it is seen that the effects reported were in the main those produced by the extract of marihuana taken by mouth. With the extract, the absorption is gradual and the action persists as long as the active principles are circulating throughout the body. The doses given were fixed ones and once taken the effects were beyond the subjects' control. Giving the extract thus afforded a longer period for study and insured greater accuracy in dosage. In New York, as far as is known, marihuana is rarely if ever taken in this form but is smoked in cigarettes. However, it is shown in the study that the effects from smoking correspond in kind to those from the extract. The difference is that, in smoking, the effects come on promptly and are of much shorter duration. How marked the reaction becomes depends on the number of cigarettes smoked and this is entirely under the subjects' control. The sensations desired are pleasurable ones—a feeling of contentment, inner satisfaction, free play of imagination. Once this stage is reached, the experienced user realizes that with further smoking the pleasurable sensations will be changed to unpleasant ones and so takes care to avoid this.