Acute Toxicity of Δ⁹-Tetrahydrocannabinol in Rats and Mice¹

Summary

Crude Thailand marihuana was extracted by the method of Turk. Initial purity of the Δ⁹-THC after extraction was 99+% as determined by nuclear magnetic resonance, mass spectroscopy, and gas-liquid chromatography.
Purity of the compound prior to administration was unchanged as determined by gas-liquid chromatography. Using 10% Tween 80
as a suspension vehicle, LD₅₀ values were determined in rats and mice. Values obtained were: rat, iv, 28.6 mg/kg: ip, 372.9 m.g/kg; ig, 666.1 mg/kg; mouse,
iv, 42.47 mg/kg; ip, 454.5 mg/kg; ig, 481.9 mg/kg. Toxic signs preceding death in both animal species included ataxia, hyper-excitability,
depression, loss of righting reflex and dyspnea progressing to apnea. Following intravenous administration in rats or mice,
death occurred within 15 min whereas following intraperitoneal or intragastric administration, death resulted between 10 and
36 hr. Tremor, diarrhea, and lacrimation were observed as additional toxic signs following ig and ip administration of Δ⁹-THC in rats. Diarrhea was an additional toxic sign observed following ig and ip injections in mice and a Straub-tail was
noted only after iv administration in mice.