Finn Sandberg

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

Abstract Δ1-Tetrahydrocannabinol-3H 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-3H are excreted in the urine. The half-life of radioactivity in blood after i.v. injection of Δ1-tetrahydrocannabinol-3H ranged from 7 to 16 min. The compound is rapidly metabolized and 30 min after i.v. administration of †1-tetrahydrocannabinol-3H, 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-3H 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.

Binding of δ1-tetrahydrocannabinol to human plasma proteins

Abstract The binding of tritium-labelled Δ1-tetrahydrocannabinol to human plasma proteins in vitro was studied with electrophoretic techniques. Δ1-Tetrahydrocannabinol was found to be associated to 80–95 per cent with lipoproteins.

Quantitation of Δ1‐tetrahydrocannabinol in plasma from cannabis smokers

A method to identify and accurately measure non‐labelled Δ1‐tetrahydrocannabinol (Δ1‐THC) in blood of cannabis smokers has been developed. It consists of the following steps: To a 5 ml plasma sample is added deuterated Δ1‐THC (Δ1‐THC‐d2) as internal standard. After extraction with light petroleum and evaporation, the Δ1‐THC containing fraction is separated by chromatography on Sephadex LH‐20 (1 times 40 cm) using light petroleum‐chloroform‐ethanol (10:10:1) as eluant. A fraction containing Δ1‐THC is collected and subjected to mass fragmentography (LKB 9000; 3% OV‐17/Gas‐Chrom Q; 230°). The mass spectrometer was adjusted to record the intensities of m/e 299 and 314 of Δ1‐THC and m/e 301 and 316 of Δ1‐THC‐d2. The standard curve was made by plotting peak height m/e 299/m/e 301. Peak levels of 19–26 ng ml−1 were reached within 10 min after smoking a cigarette containing 10 mg Δ1‐THC.

Elimination of tritium-labelled cannabinols in the rat with special reference to the development of tests for the identification of cannabis users

Abstract A method is described for the preparation of tritium-labelled Δ9-tetrahydrocannabinol and other cannabinols. Intravenously injected Δ9-tetrahydrocannabinol-H3 is eliminated very slowly by the rat; half of the administered dose still remained in the body after one week. About 80 per cent of the drug is excreted in metabolized form via faeces, the remainder being eliminated also as metabolites in the urine. During the first 24 hr 2–6 per cent of the injected activity appears in the urine, but less than 0.006 per cent of the dose, if any, is excreted unchanged. A considerable amount of the activity is readily extractable with ether and possibly an identification method for Cannabis-users may be based on the occurrence of this metabolite. Δ9-Tetrahydrocannabinol is apparently not excreted as a glucuronide.

Biliary excretion of Δ1-tetrahydrocannabinol and its metabolites in the rat☆

Abstract Δ1-Tetrahydrocannabinol (Δ1-THC) administered i.v. (1 mg/kg) to anaesthetized rats with cannulated bile ducts is rapidly eliminated as metabolites in the bile. 60–70 per cent in 6 hr. In comparison with the slow excretion via faeces an extensive enterohepatic circulation, which may be of toxicological importance, is indicated. Unchanged Δ1-THC and cannabinol are eliminated in low amounts (0.05 0.1 percent) in the bile. A few per cent consists of two or more mono-oxygenated metabolites. neither of which is identical with 7-hydroxy-Δ1-THC or 6-β-hydroxy-Δ1-THC. The main part of the non-conjugated metabolites is present as compounds more polar than 7-hydroxy-Δ1-THC and as carboxylic acids. These acids were more polar than Δ1-THC-7-oic acid which could not be identified in a free or conjugated form. In the rat about 60 per cent of the metabolites are eliminated as water-soluble conjugates. Hydrolysis with glucuronidase liberated aglycones which were mainly neutral whereas hydrolysis with alkali released neutral but also some acidic compounds. 7-Hydroxy-Δ1-THC was identified as an aglycone of glucuronic acid and furthermore, three mono-oxygenated cannabinoids were isolated after hydrolysis and partially characterized.