Alterations in the pharmacokinetics of 3H-delta9-tetrahydrocannabinol in mice by bacterial endotoxin

Mice were pretreated with either bacterial endotoxin (3 mg/kg, ip) or saline 3 hr prior to an ip injection of 100 mg of 3H-delta9-tetrahydrocannabinol (3H-delta9-THC) per kg, a combination that results in synergistic lethality. Five hours after the injection of 3H-delta9-THC, the endotoxin-pretreated mice contained a significantly greater amount of radioactivity in kidney, liver, heart, plasma, urine, and brain than those without pretreatment. However, the plasma and brain levels of the animals tested with both endotoxin and 3H-delta9-THC (100 mg/kg) were significantly less than those in mice treated only with 200 mg of 3H-delta9-THC per kg, a sublethal dose. The percentage of radioactivity corresponding to unchanged 3H-delta9-THC in extracts of livers and brains was significantly greater in the endotoxin-pretreatment group than in controls. The brain level of 3H-delta9-THC in the endotoxin-pretreated mice was 50% higher than that in the saline-pretreated mice 5 hr after 3H-delta9-THC (100 mg/kg) administration. However, the brain levels of 3H-delta9-THC in the mice treated with endotoxin and 3H-delta9-THC (100 mg/kg) was one-third of that in brains of mice receiving the LD50 of 3H-delta9-THC (300 mg/kg).