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DR. MUNCH: So far as the external effects are concerned of the fluid extract of Cannabis, the effects are hyperesthesia, fomication, and cold extremities. These cause increase in intensity. It is not local.

So far as the gastro-intestinal tract is concerned, there is no effect upon the taste. There is a tendency towards an increase in thirst and appetite, and large doses will cause nausea, emesis, vomiting, and the drugs produced diarrhea or constipation.

So far as the effect on the brain, I am only going into that to this extent, to say that in connection with USPVIII which was thirty years ago we were interested in knowing whether the American grown plant could be used as well as that which had been imported from India. The study made by the American Drug Manufacturers Association and by others at that time led the USP official Committee to the stand that either the Indian or the American grown material would be comparable for medicinal purposes so long as it was tested and found to have a certain physiological effect, and from a number of bio-tests that were made in which the material was administered to dogs, there were three different effects produced, one
effect being to cause the dog to sway from side to side, and back and forth, and finally not to be able to stand erect at all. It was then that satisfactory material was produced which would produce such a response.

When it became necessary to prepare revised standards for world use of the Cannabis, we standardized the standards. First, we obtained material from various manufacturers in this country representing the ordinary strength or potency of the product and then many of these
manufacturers told me of the material of ten or twenty or thirty years before, and they gave me the products or materials which were of the same commercial strength as they have always been marketing.

Then through various means, we obtained drugs and standardized those products, that is thirteen different products of this series of drugs. Those products were then mixed, and constituted the USP fluid extract of Cannabis, which was officially recognized in USP X.

Then as to the method of bio-assay. Contrary to much of the published literature we find that dogs vary as greatly in their response as do humans. On. some 500 dogs I have used, fully one-half were very insensitive, and were discarded immediately. The nervous type or short-haired dog is usually a satisfactory animal but not necessarily the best.

Going back to the pharmacological action, so far as the causes, and effect on circulation, a small dose causes rapid beating of the heart which may be followed by less than normal. The blood pressure is usually unchanged, or there is a slight fall.

So far as the blood is concerned, there is a definite increase in the hypoglycemiacal content. At the same time, there is a definite increase in the blood sugar. Enormous doses have produced death by cardiac failure, but the doses were 100 to 200 times doses, which produced a tremendous physiological effect.

If smoked, there is a tendency to choking or coughing, and all doses tend to decrease the respiratory needs. So far as the muscles are concerned, the muscles show a definite confusion, and with very large doses there are shown flexor spasms. But not with a therapeutic dose.

So far as the pupils of the eyes themselves, there is a very definite contraction of the conjunctiva, and usually but not always a dilation of the pupil.

So far as the effect on the glands, there is probably a double diuretical effect. There is a question, and the production of the diuretic effect is unsettled.

It has been reported there is a sexually stimulating effect. Some say it does and some say it does not exist.

So far as antidotes are concerned the thought is, if it has been swallowed, the administration of an emetic, caffeine or acid drinks in general.

So far as the habituation is concerned, it has been claimed and denied, and so far as elimination is concerned, I have not been able to detect it in the urine. So, I do not believe the active principle is eliminated by urine.

In the general pharmacopoeia developed by O'Shaunessy in 1843, which reached its peak ten or fifteen years later, it was clinically recommended for all sorts of diseases and later found worthless.

There is a definite decrease in the central Indian drug which stimulated further work done by Casparis and others, after which it appears to have gone into innocuous desuetude until it began to be criminally exploited, which led to the present burst of study.

Pharmacology is right I think, when it is said it does not have the same effect, or one effect on the brain, and I may be sticking my head out when I make a suggested answer that the cause of the awful intoxication is largely due to the difference in the rate of absorption, whether the material is smoked or given by solution or in capsules and taken into the stomach, or given rectally, and also the susceptibility on the brain, because in many instances we have given the same material to humans or dogs. Some of the animals it has shown no effect upon, others it has shown an enormous effect with the same dose. So far as animals are concerned, we have made a comparative study and find that dogs and rabbits have proven most suitable for quantitative assays but none can be relied on for qualitative accuracy, that is 10 to 12%. That is a complete
change from what I said in my book,1 but it is possible, by running from 14 to 20 bio-assay, to obtain results accurate within plus or minus 11 to 20%. But, it never has been done commercially and can only be done in connection with research.

Through what channels does the active principle find its way into the nerve centers? I should say through the blood. So far as the effect on the blood pressure, I have attempted to cover those reflex changes. It has been stated and denied that there are significant lesions in the brain of humans. Dogs I have used for some years, in some instances showed certain types of brain changes. Whether those are connected with Cannabis, I do not know. I am trying to complete
that now and perhaps within the next five years I can answer the question.
Regarding the other questions, I would rather refer those to Dr. Bromberg.

COMMISSIONER ANSLINGER: Before we enter into a general discussion, I would like to call on Dr. Loewe of Cornell University to give us a statement on the bio-assay method.


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