Study of the pharmacology of hashish

Sections

Summary

Details

Author: G. Joachimoglu , C. Miras
Pages: 7 to 8
Creation Date: 1963/01/01

Study of the pharmacology of hashish

Prof. G. Joachimoglu
Priv. Doz. C. Miras

There is no plausible explanation for the fact that the six plants which contain caffeine ( Coffea arabica, Camelia thea, Cola acuminate, Paulinia sorbilis, Ilex paraguayensis, Theobroma cacao) were discovered by different peoples having no knowledge of chemistry and pharmacology. The natives of central Africa used cola nuts and the natives of South America the leaves of the Ilex paraguayensis (Paraguay tea) at a time when no communication existed between Africa and America.

Different peoples have also shown us the most effective way to prepare beverages out of the natural drugs. Coffee beans are roasted, thus releasing volatile, aromatic compounds which are not contained in the plant. These give coffee its agreeable smell and flavour. Roasting is used only in the case of coffee beans. This process is not employed for any of the other drugs containing caffeine.

It therefore appears that different peoples, possessing no knowledge of chemistry and pharmacology, not only discovered those plants in the vegetable kingdom which contain caffeine, but also developed processes for preparing beverages which are pleasant to drink.

Opium is either taken orally, or smoked. Once the alkaloid morphine had been isolated from opium, some opium eaters and smokers became morphine addicts.

Tobacco leaves are rarely taken orally. They are mostly smoked. A tobacco smoker absorbs not the active constituents of the tobacco, but the substances contained in the smoke.

For the above reasons, it appeared to us worth while to ascertain by experiment whether hashish smoke contains any pharmacologically active constituents and to determine the comparative effectiveness of hashish smoke and natural hashish.

We have not found any study on the pharmacology or chemistry of hashish smoke in the literature of the subject.

In order to extract the solid constituents of hashish smoke, we used an apparatus which has been employed frequently in recent years for testing cigarette smoke. With this apparatus it is possible to simulate the burning of a hashish cigarette in the mouth of a hashish smoker.

The products of combustion are deposited in a glass tube in which the inhaled particles are electrostatically precipitated in the form of a sublimate. The sublimate can be brought into solution from the surface of the glass tube. It is possible to control the number and duration of the inhalations. 1

The next step was to decide how to test the pharmacological effectiveness of natural hashish and the hashish sublimate obtained from it. This called for the solution of two problems: how to prepare a solution of the active constituents of both substances, and how to test them on laboratory animals.

A paper which was published in this periodical 2 contains the following observation: "It may be possible to dissolve the active constituents of cannabis in a neutral oil and to inject the solution intraperitoneally. With oily solutions of camphor, the full effects of the camphor can be observed very quickly."

We followed this suggestion. For the preparation of the solutions, the substances (natural hashish and hashish sublimate) were treated with petroleum ether or ether containing no peroxides.

This solution was suspended in olive oil and the organic solvent (petroleum ether or ether) was removed in a vacuum. We thus obtained a solution as mentioned above, suitable for intraperitoneal injection in laboratory animals (rats and mice).

With these solutions we ascertained the LD 50 on mice for natural hashish and for hashish sublimate obtained from it.

We followed the method of Trevan & Gaddum 3 and used six groups of ten laboratory animals each for each test.

The experimental results of four hashish tests are shown in table I.

1

1 The Ethel MK VII Smoking Machine may be obtained from Cigarette Components Ltd., Friendly House, 21-24 Chiswell St., London, E.C. 1. Instructions for the operation and maintenance of this apparatus are given in the operation and service manual supplied by the -above-mentioned firm.

2

2 G. Joachimoglu, Bulletin on Narcotics, vol. XI, No. 3, 1959, p. 6:

a

3 See J. Burn, Biological Standardization, Oxford Press, 1951.

TABLE I

 

LD 50 for mice (mg-g mouse)

Source and age of the hashish

A. - Natural hashish

B. - Hashish sublimate

(1) Pharmacological Institute
   
Less than 20 years
2.5 10.5
(2) Pharmacognostical Institute
   
Less than 10 years
3.5 17
(3) Laboratory for Forensic Medicine
   
Less than 40 years
0.3 1
(4) Police museum
   
( a) Less than 2 years
0.94 3.2
( b) Less than 20 years
1.35 5.1

It will be seen from the table that the different samples of hashish revealed a considerable range of effectiveness. Age is of no particular importance, since the hashish used in test 3 (Laboratory for Forensic Medicine) proved to be the most effective of all those tested. It will also be observed from the table that the sublimates used in the tests proved three to five times weaker than the natural hashish from which they were obtained. We are unable to explain this decrease in effectiveness. It may be that some of the pharmacologically active constituents are destroyed when the hashish is smoked. The possibility cannot be excluded, however, that when the hashish is smoked, substances are created which are not contained in the drug itself, as occurs when tobacco leaves are smoked. This problem can be solved only by a detailed chemical analysis of hashish sublimate.

In studying animals intoxicated with hashish, it is possible to distinguish between a stage of excitement 4 and a stage of paralysis. Slight degrees of paralysis of the central nervous system can be determined by various tests. If the animals are placed on a stick and the latter is rotated with the fingers, the control animals do not lose their balance, whereas animals which have been given hashish fall off. The control animals can swim in water. After being injected with hashish, the animals cannot keep themselves above water. As soon as they sink and swallow water, they try with ataxic movements to reach the surface.

The effect on the central nervous system is also manifested by low motility and an ataxic gait.

Symptoms of cannabis-induced excitement in human beings were described as early as Herodotus. (See G. Joachimoglu, Heffter's Handbuch der Pharmakologie, vol. 2, 1924, p. 1114.)

In a second series of experiments, we tested a sample of hashish (4 ( a) of table I) on mice and rats, and ascertained the minimum dose producing pharmacological effects. The results are shown in table II.

Table II shows, in agreement with the results of table I, that hashish sublimate has a weaker effect on both mice and rats. The minimum doses which produce pharmacological effects are also smaller in the case of natural hashish than in the case of hashish sublimate.

We have tested the corneal reflex in rabbits, using the calibrated hair test developed by Frey to test the sensitivity of the cornea. After the injection of hashish solutions, the sensitivity of the cornea decreases. Unfortunately, the results are not consistent, so that it is difficult to compare the effectiveness of hashish sublimate with natural hashish.

TABLE II

 

Minimum dose producing pharmacological effects (mg-g animal)

 

LD 50 (mg-g animal)

A. - Natural hashish

B. - Hashish sublimate

Laboratory animal

A. - Natural hashish

B. - Hashish sublimate

I

II

III

I

II

III

Mouse
0.94 3.2 0.3 0.3 0.18 0.54 0.9 0.54
Rat
0.8 3 0.54 0.54 0.5 2
2
2

I = Rotating stick test.

II = Swimming test.

III = Loss of motility, ataxic movements.

Summary

  1. The analysis of hashish sublimate obtained, by suitable means, from natural hashish is important for the study of cannabis, since the hashish smoker absorbs only the substances which are contained in the hashish smoke.

  2. In order to make a pharmacological comparison between natural hashish and hashish sublimate, it is desirable to dissolve their active constituents in oil. Laboratory animals can be injected intraperitoneally with the solutions thus obtained.

  3. Some standard preparation is absolutely necessary, in order to ensure uniformity of hashish preparations.

These experiments were carried out in the research laboratories of the University Clinic for Therapy. We extend our most sincere thanks to the Director of the Clinic, Professor V. Malamos, for his courtesy.