On the metabolism of tritium-labelled Δ1-tetrahydrocannabinol in the rabbit☆

Abstract Δ1-Tetrahydrocannabinol- 3 H is almost completely metabolized to more polar metabolites after intravenous (i.v.) injection in the rabbit. About 35 per cent of the dose is excreted in the urine during the first 24 hr as compared to only 10 per cent in the faeces. A considerable amount (4–10 per cent) of the radioactivity excreted in the 24-hr urine is extractable with ether and upon acidification of the urine the extractable amount increases four times or more. At least three major metabolites of Δ1-THC- 3 H are excreted in the urine. The half-life of radioactivity in blood after i.v. injection of Δ1-tetrahydrocannabinol- 3 H ranged from 7 to 16 min. The compound is rapidly metabolized and 30 min after i.v. administration of †1-tetrahydrocannabinol- 3 H, only 3–4 per cent of the radioactivity in the blood is due to unchanged compound. The blood level of an ether-soluble metabolite reaches its maximum 0.5–2 hr after injection. Thus, the formation of a pharmacologically active metabolite cannot be excluded at present. The distribution of radioactivity in tissues largely reflect the elimination of Δ1-tetrahydrocannabinol- 3 H through liver and kidneys. Brain and spinal cord show the lowest activity levels of all the investigated tissues. Three days after administration high levels of radioactivity still persist in body fat and spleen.