208 REPORT OF THE INDIAN HEMP DRUGS COMMISSION, 1893-94. [APP.

                                  D.—PHYSIOLOGICAL INVESTIGATION.

As directed in your letter above quoted, the first object of the physiological investiga-
tion was to ascertain the smallest dose of the alcoholic extract of the standard ganja which
could be relied on to produce definite physiological effects. This having been learnt, the next
part of the enquiry was to test the other samples by means of the knowledge thus acquired.
Definite physiological action is understood to mean the production of such effects as are
capable of clear recognition and definite description. In an investigation of this kind the drug
must necessarily be administered to many animals of different weights; consequently if the
results produced are to be of any comparative value, the doses given must always bear a
proportion to the animal's weight.

It became evident, as the enquiry proceeded, that the same proportional dose could not
be relied on to produce absolutely similar symptoms in different animals even of the same
species. In different animals, even of the same species, the symptoms varied, not only in
character, but also in degree. Further, the occurrence of symptoms of one kind either mask-
ed the occurrence or prevented the development of those of another.

Accordingly, the object aimed at was the discovery of the smallest proportional dose
constantly attended by some definite physiological effect as opposed to marked physiological
effect, and without desiring to produce effects of a constant type in every instance. The
first duty was evidently to obtain by experiment some definite conception of the physiological
action of the drug in small doses that may be termed minimal, and the need for this will
become more apparent when the somewhat varying character of its action is described.
The account of the physiological investigation is therefore naturally divided into-

1.  The description of the physiological action of the drug as tested by means of the-
alcoholic extract of the standard ganja in minimal doses.

2.  Adoption of a certain quantity of this substance proportional to the body weight
as a standard minimum dose.

3.  The physiological testing of the other samples of ganja as compared with the
standard ganja.

Twenty-three administrations of the standard alcoholic extract were made before satis-
factory minimum dose could be arrived at. One hundred and sixty-one administrations of the
extract of the other hemp drugs were required in the work of testing their relative physiologi-
cal properties. The animals utilised throughout were cats.

The weights of the cats and of the required doses of the extracts were taken according to
the Avoirdupois scale. The method of administration was as follows:-

The animal was first carefully weighed in a bag of known weight, and then the required
dose calculated from its body weight. The dose of the alcoholic extract was weighed out in
a tared capsule, dissolved in a little alcohol and made into an emulsion with starch, the spirit
being subsequently driven off by heating the emulsion thus formed on the water-bath. The
emulsion was introduced into the stomach by means of a syringe and a small œsophageal tube.

Control experiments were made to test whether any portion of the effect produced might
be due to alcohol retained in the emulsion. It will be seen from the record of the experiments
that the amount of alcohol used produced no result when administered to cats.

A limited number only of cats was obtainable, that is, of cats suitable for experiments
of the kind required; for it was important that they should be fairly tame and docile, well
nourished and, if females, not pregnant: pregnancy would interfere with the correct body
weight. The same animals were in consequence repeatedly utilised, a sufficient interval
being allowed to elapse between consecutive doses.

1. PHYSIOLOGICAL ACTION OF THE DRUG AS TESTED BY MEANS OF THE ALCOHOLIC EXTRACT
OF THE STANDARD GANJA IN MINIMAL* DOSES.

It will be better to describe, first, the nature of the effects produced by the drug, and then
give in detail the experiments upon which this account is based. The symptoms observed
roughly resolve themselves into three types, and subject to variation induced by idiosyncrasy,
it may be said that the smallest dose of the drug capable of producing any appreciable effect
will produce symptoms belonging to the first two types, or the dose being increased will
induce symptoms of the first and third type, with a passing manifestation of those of the
second. I have given the three types the following definition:—

(a) Symptoms of distress.

(b) Phenomena indicating disturbance of the sensory-motor mechanism.

(c) Soporific or narcotic effects.

* Note.— The term minimal doses as opposed to the minimum dose is adopted in order to indicate that all the doses
given were small, the largest being 1/65,000 of the body weight. The investigation is consequently restricted to the
observation of the phenomena induced by such doses, and not by larger doses.