Factors affecting the response of the female rat reproductive system to cannabinoids

Chronic oral administration of either crude marihuana extract (CME) or Δ 9-tetrahydrocannabinol (THC) to female Fischer rats for 64–72 days, at a dose approximating heavy usage by humans, reduces food intake by about 8%. Pair-feeding studies demonstrate that this decreased food intake accounts for previously described decreases in uterine and ovarian weights, which are much more affected by food restriction than is body weight. THC-treated rats lost weight initially which was not regained. Pair-fed rats gained only about one-half of the weight of the untreated control or vehicle-treated control rats over a 64-day period. Although long-term cannabinoid administration leads to tolerance and the resumption of the estrous cycle, the onset of estrus is often delayed when cannabinoid is administered 5–6 hr before the proestrus luteinizing hormone (LH) surge. Our results indicate that although chronic exposure to cannabinoids can continue to affect the rat estrous cycle, they do not have a direct effect of growth of the reproductive organs. The results reemphasize the need for adequate nutritional controls in marihuana and other toxicological research.