Effects of delta 9-tetrahydrocannabinol during the follicular phase of the rhesus monkey (Macaca mulatta).

It is well documented in the literature that delta 9-tetrahydrocannabinol (THC) decreases serum concentrations of pituitary gonadotropins in several species. To study its effects in the menstrual cycle of regularly cycling rhesus monkeys, 2.5 mg/kg THC were administered to five animals from days 1-18 of the cycle [ovulation day in our colony, 15 +/- 1 day (mean +/- SD)]. Controls received vehicle (Tween 80 and saline) in an identical protocol. Animals were bled daily or every other day, and serum total estrogens, LH, PRL, and progesterone were determined by RIA. Serial laparoscopies were performed to visualize ovulation. Whereas animals treated with vehicle presented normal cycle lengths (26, 26, 29, 30, and 34 days), those treated with THC presented abnormal lengths (145, 76, 22, 94, and 59 days). All vehicle-treated cycles were ovulatory, while four of five THC cycles were anovulatory (P < 0.02). Five THC-treated animals were anovulatory in the posttreatment cycle. To determine the site of action of THC-induced anovulation, five animals received THC, human menopausal gonadotropin, and hCG simultaneously. All ovulated normally, as determined by laparoscopic visualization of stigma. Normal luteal phases were evidenced by normal luteal phase lengths and serum progesterone concentrations. These findings are of clinical relevance, since they were achieved with doses of THC that produce blood concentrations similar to those found in heavy marijuana users.