Endocrine effects of marijuana in the male: preclinical studies

Marijuana affects a variety of hormones that are regulated by hypothalamic function and it appears that the psychoactive ingredient, THC, is the major compound responsible for this action. It is probable that THC affects these hormones through its ability to alter various neural transmitters in the hypothalamus or neural transmitters in the CNS which impinge on the hypothalamus. The dopaminergic and serotonergic fibers seem to be particularly important. The two gonadotropins, LH and FSH, secreted by the pituitary gland are of major importance to reproduction in the male. Both gonadotropins appear to respond to a single releasing factor from the hypothalamus, GnRH, which is sensitive to catecholamine neurotransmitters. The THC-induced block of GnRH release results in lowered LH and FSH which is responsible for reduced testosterone production by the Leydig cells of the testis. Other hormones that might have a synergistic or antagonistic effect upon reproduction in the male are the adrenal cortical hormones, prolactin, thyroid hormones, and growth hormones. THC appears to depress prolactin, thyroid gland function, and growth hormone while elevating adrenal cortical steroids. Chronic exposure of laboratory animals, such as rats, mice, and monkeys to marijuana and to the various cannabinoids in marijuana has altered the function of several of the accessory reproductive organs. Reports of reduced prostate and seminal vesicle weights, as well as altered testicular function, have been partially explained by the effect of marijuana in lowering serum testosterone needed for proper function and support. Although some of the change in organ weight may be due to lowered testosterone production by the Leydig cells of the testis, some of the weight changes may be due to a direct action of THC, and perhaps some of the other nonpsychoactive cannabinoids in marijuana, on the tissue themselves. Also, of concern are the reports that acute cannabinoid treatments affects the quality and quantity of spermatozoa produced by the testis. The question is still unanswered as to whether or not the effects observed on spermatozoa are due to a direct action of the cannabinoids on spermatogenesis, or whether some of the observed effects may be due to altered hormone levels which are necessary for the support of spermatogenesis. Reduced testosterone and FSH may be important in producing the observed changes in sperm production by the seminiferous tubules. Many of the effects on the endocrine system caused by chronic treatment of animals with THC are completely reversible with time and there is reason to believe that tolerance develops to these effects with acute exposure to THC.(ABSTRACT TRUNCATED AT 400 WORDS)