Tolerance develops to the disruptive effects of delta 9-tetrahydrocannabinol on primate menstrual cycle

Long-term exposure of sexually mature female rhesus monkeys (Macaca mulata) to thrice weekly injections of delta 9-tetrahydrocannabinol resulted in a disruption of menstrual cycles that lasted for several months. This period was marked by an absence of ovulation and decreased basal concentrations of gonadotropin and sex steroids in the plasma. After this period, normal cycles and hormone concentrations were reestablished. These studies demonstrate that in rhesus monkeys subjected to long-term treatment with delta 9-tetrahydrocannabinol tolerance develops to the disruptive effects of the drug on the menstrual cycle.