STATEMENT OF DR. S. LOEWE

PHARMACOLOGIST
CORNELL UNIVERSITY MEDICAL COLLEGE

DR. LOEWE: The bio-assay, in my opinion, is the point where the pharmacologist has to enter this manifold picture at which we arrive in this conference for a very significant reason.

The reason is that all the manifold aspects of Marihuana are focused around and makes the existence of an active principle in this drug, active principles which are chemically not known, and as long as an active principle is not chemically known, it can only be determined from its
action, that is, biologically, which can only be by bio-assay.

Dr. Munch has thoroughly depicted the many aspects of the pharmacological action of Marihuana. That is what we can call the pharmacological spectrum of this drug, But it must be emphasized, that the spectrum of the drug as such and not on one certain active principle
necessarily, for nobody knows the active principle, and nobody ever knows whether there is only one active principle or more than one active principle.

It can be assumed from the beginning that there is more than one active principle but this must not necessarily concern the Marihuana interests, because the problem is narrowed to that active principle among possibly many active principles which produces the narcotic or "dope" action in humans.

Even with respect to this point, of course, we are not one hundred percent sure that this is the action of one principle or more than one.

Quantitative bio-assay of the active principle of Marihuana, of course, tends or aims to determine that one active principle or a complex of active principles, which is interesting from the human point of view, the narcotic principle. May I mention right here that as long as we do not know how many active principles there are, we have to assume primarily that every action is carried by a separate active principle, and with this assumption, may I speak for the definite ataxia principle, which is the principle which can be bio-assayed in the drug which produces the main action stored in the dog. There is another action in the drug, which I may call the depressant action, the cataleptic action, and then there is the anesthetic principle which can be studied in the rabbit, using the depression of the corneal reflex. The depressant action in the mouse, manifested by prolonging the hypnotic action, is an action which I have observed and used to bio-assay this one active principle.

Now, bio-assay has to start, therefore, with this, which one of these actions is preferable for the Marihuana problem for studying the narcotic principle, important for humans?

We have much evidence that the ataxia action is fairly well related to the narcotic action.

In detail, there is not much to say. Walton has elaborated the previous effects and experiences of the bio-assay of the drug in a fairly good manner. There are details, and certainly it is necessary to bio-assay a large number of animals due to the individual natures and non-
susceptibility which complicates the actions, and action can only be compared in one and the same animal, and only for comparison in a single animal, and the consequence is that a large group of animals has to be used.

The mode of administration has been emphasized by Dr. Munch. I would prefer and do prefer, for bio-assay, intravenous administration because the Marihuana action has a very long period of latency without the means of elimination from the system, so that the results seem to be
fairly well comparable.

Now, I am of the opinion, just like Dr. Munch has emphasized, that the bio-assay method of the drug is not definitely eliminated. I have the impression that the method will result in fairly good accuracy, but it is an accuracy of plus or minus 15 or 20%, and which will suffice, I suppose, for the period in which bio-assay is necessary.

It is the unfortunate situation of the pharmacologist that in certain periods of development of active principles he is available for the purpose, and in a certain sense he is the man charged with the entire problem. But, his unfortunate situation is that just when he has developed this method and applied it, it is always finally inherent that he is out of the picture for, as soon as the chemist comes into the picture, and the bio-assay is not any more necessary, the pharmacologist can be dropped. If I may mention this at random, all of these points of view are true also as to the chemical test. Before the chemist has developed the active principle, the chemical method of
identification of much or great importance to the country, and they may be of much or less importance for identifying the active principles than are the bio-assay methods, but only after the discovery of the active principle and its chemical properties, the problem of the chemical test, the importance of the Beam test can become clear.
I know of another example where a greater activity of a certain drug was found, and the drug was not white but yellow, and this, of course, introduced many beliefs that yellow colors and opticals would be an easy expedient for getting a quantitative activity. So, there was developed a number of tests for this drug, going into this problem, but finally it turned out what general color of the narcotic or commodity was and the reason for the high activity of the drug.

COMMISSIONER ANSLINGER: Well, Doctor, we are going to have the chemists confer among themselves, and they will then give us some of their views. I think we can reserve the general discussion for the afternoon.

We will now hear from Dr. Walter Bromberg, Senior Psychiatrist of the Department of Hospitals, City of New York.