Abstract

1. The acute toxicity of the highly marihuana-active natural charas tetrahydrocannabinol (acetate), its somewhat less active synthetic homolog, parahexyl, the feebly active hemp component cannabinol, and the inactive hemp component cannabidiol was studied in mice, rabbits, guinea pigs, cats and dogs.

2. The L.D.₅₀ of all four substances was very high as compared with the dose causing specific symptoms, namely, over 10.0 gm./kg. in mice by mouth and still higher subcutaneously, and between 100 and 230 mg./kg. by vein in mice, rabbits and dogs.

3. The ataxia activity varies widely in different species of animals. Corneal areflexia is elicited only in rabbits. The only sign of marihuana action common to all species of animals is a cataleptic effect. The only consistent circulatory effect in dogs was a moderate decrease in pulse rate. Excessive oral doses in mice produce diarrhea.

4. Hypnotic action is completely absent in all four substances in all species.

5. Lethal effects and specific pharmacologic activity are not correlated. The four substances vary greatly in ataxia potency, but little in lethal dose. Dogs die from pulmonary edema after intravenous administration. One dog succumbed from intestinal hemorrhage following parahexyl given by mouth.