TOXICITY AND CARCINOGENICITY OF DELTA(9)-TETRAHYDROCANNABINOL IN FISCHER RATS AND B6C3F1 MICE

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) was studied for potential carcinogenicity in rodents because it is the principal psychoactive i ngredient in marihuana and it has potential medicinal uses. Delta(9)-T HC in corn oil was administered by gavage to groups of male and female Fischer rats and B6C3F1 mice at 0, 5, 15, 50, 150, or 500 mg/kg, 5 da ys a week for 13 weeks and for 13-week plus a 9-week recovery period, and to groups of rats at 0, 12.5, 25, or 50 mg/kg and mice at 0, 125, 250, or 500 mg/kg, 5 times a week for 2 years. In all studies, mean bo dy weights of dosed male and female rats and mice were lower than cont rols but feed consumptions were similar. Convulsions and hyperactivity were observed in dosed rats and mice; the onset and frequency were do se related. Serum FSH and LH levels in all dosed male rats and cortico sterone levels in 25 mg/kg female rats were significantly higher than controls at 15 months in the 2-year studies. Delta(9)-THC administrati on for 13 weeks induced testicular atrophy and uterine and ovarian hyp oplasia; the lesions persisted in a 9-week recovery period. In the 2-y ear studies, survival of dosed rats was higher than controls; that of mice was similar to controls. Incidences of testicular interstitial ce ll, pancreas and pituitary gland adenomas in male rats, mammary gland fibroadenoma and uterus stromal polyp in female rats, and hepatocellul ar adenoma/carcinoma in male and female mice were reduced in a dose-re lated manner. Decreased tumor incidences may be at least in part due t o reduced body weights of dosed animals. Incidences of thyroid gland f ollicular cell hyperplasia were increased in all dosed groups of male and female mice, and follicular cell adenomas were significantly incre ased in the 125 mg/kg group of males, but there was no evidence of a d ose-related trend in proliferative lesions of the thyroid. There was n o evidence that Delta(9)-THC was carcinogenic in rats or mice. (C) 199 6 Society of Toxicology