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[Review and update: marijuana and reproduction].


 Longterm use of marijuana has been found to cause physiological changes that can alter individual reproductive potential. The effects of marijuana depend on the dose and can include death from depression of the respiratory system. Longterm effects are however particularly hard to assess. Marijuana is absorbed rapidly and eliminated very slowly. The active principle, delta-9-tetrahidrocannabinol (delta-9-THC), is highly liposoluble and fixes to the serum proteins, passing to the lungs and liver for metabolization and to the kidneys and liver for excretion. As with estrogens, there is an enterohepatic circuit for reabsorption and elimination. 90% is eliminated in the feces, 65% within 48 hours. Because of the enterohepatic circuit and liposolubility, elimination requires 1 week for completion. The other important biotransformation of the active principle is hydroxilation; the hydroxilated derivatives are responsible for the psychoactivity of cannabis. Cannabis affects both neuroendocrine function and the germ cells. Studies on experimental animals have indicated that THC can cause a decline in the pituitary hormones follicle stimulating hormone, luteinizing hormone, and prolactin, and in the steroids progesterone, estrogen, and androgens. Human studies have shown that chronic users have decreased levels of serum testosterone. Because steroidogenesis can be restimulated with human chorionic gonadotropin, it appears that THC does not directly affect steroid production by the corpus luteum, but that its action is mediated by the hypothalamus. Because of its potent antigonadotropic action, THC is under study as an anovulatory agent. The same animal studies have shown that ovulation returns to normal 6 months after termination of use. High rates of anovulation and luteal insufficiency have been observed in women smoking marijuana at least 3 times weekly. THC accumulates in the milk. Animal studies have shown that THC depresses the enzymes necessary for lactation and causes a diminution in the volume of the mammary glands. In recent studies, significant amounts of the drug have been detected in both mothers' milk and the blood of newborns. Animal studies indicate that THC crosses the placenta, achieving concentrations in the fetus as high as those in the mother. Animal studies also demonstrated increasing frequency of abortions, intrauterine death, and declines in fetal weight. The effects were probably due to an alteration in placental function. A human study likewise showed that marijuana use during pregnancy was significantly related to poor fetal development, low birth weight, diminished size, and decreased cephalic circumference. Congenital malformations have been observed in experimental animals exposed to THC. Declines in sperm volume and count and abnormal sperm motility have been observed in chronic marijuana users. In vitro studies show that THC produces a marked degeneration of human sperm.
