Cannabinoid-induced hormone changes in monkeys and rats.

Previous findings at various laboratories indicated that cannabinoids distribute to sexual behavior centers in the brain, and endocrine aberrations have consistently been observed in animals treated with cannabis constituents. Subacute and chronic studies were performed to monitor hormone changes in rats and monkeys exposed to marihuana smoke or pure cannabinoids. In oral studies, young Fischer rats of both sexes were given delta 9-tetrahydrocannabinol (delta 9-THC) doses of 2, 10, or 50 mg/kg for 14--180 d and pregnant rats received 1, 5 or 10 mg/kg during gestation and lactation. Other male rats were exposed to marihuana smoke at delta 9-THC doses of 2 or 4 mg/kg for 14 d. Rhesus monkeys of either sex were given oral cannabidiol doses of 30, 100, and 300 mg/kg for 90 d. Serum pituitary, steroid, and thyroid hormone levels were determined by radioimmunoassay. Marihuana smoke (and oral delta 9-THC) depressed testosterone 20--30% and triiodothyronine 17--29%. In pregnant rats, small doses of delta 9-THC suppressed luteinizing hormone, but larger doses elevated both follicle-stimulating hormone and estrogens (approximately 50--100%) without affecting progesterone levels. Prolonged oral administration of delta 9-THC to young rats tended to increase gonadotropins, to which tolerance developed in males. Cannabidiol-treated monkeys responded with slight elevations in luteinizing hormone and follicle-stimulating hormone in males, whereas steroid hormones were essentially unchanged for both sexes. Hormone imbalance may explain cannabinoid-induced embryotoxicity and impaired gonadal function.