In vivo inhibition of enterocyte metabolism by delta 9-tetrahydrocannabinol

Mice were given 10 to 100 mg/kg by stomach tube of delta 9-tetrahydrocannabinol (THC) in a single dose or for 4 consecutive days. [3H]Thymidine or [3H]glucosamine was given 3 or 24 hr before sacrifice. Enterocytes were isolated, and the incorporation of radioactivity into the acid insoluble fraction was measured. THC significantly inhibits in a dose-related fashion (from 10 to 90%) in vivo enterocyte metabolism. This inhibition is found in all enterocytes whatever their position in the intestinal tract; it is also independent of the state of differentiation of enterocytes. After a single ingestion of THC, crypt cells which synthesize DNA incorporate 37 to 45% less thymidine, and villus cells, which synthesize important amounts of glycoproteins, incorporate 15 to 39% less glucosamine. After 4 days of THC administration, the inhibition of thymidine incorporation is even more significant (up to 88%).