A series of biological studies are proposed to further explore neural and pituitary mechanisms underlying marijuana-induced suppression of gonadotropin and prolactin secretion in women. The effects of pyrolized marijuana leaf as well as marijuana placebo on gonadotropin secretion will be determined following administration of synthetic luteinizing hormone releasing hormone (LHRH) and naloxone. The effects of marijuana and placebo on thyroid hormone releasing hormone (THRH) induced prolactin release from the pituitary will also be measured. Plasma levels of Delta9-THC and 11-NOR-Delta9-THC-9 carboxylic acid (9-carboxy THC) will be assessed in these studies and convariance with palsma hormone levels will be determined. The proposed provocative studies should help clarify the physiological processes which may be affected by THC or its metabolites on hypothalamic and/or pituitary function in women. A second goal of the proposed study is to determine if the latency of manijuana-induced changes in prolactin and gonadotropin secretion during different phases of the menstral cycle with levels of Delta9THC in palsma and of 9-carboxy THC following acute inhalation of pyrolized marijuana leaf. We propose to measure Delta9-THC and 9-carboxy THC in multiple plasma samples which have been obtained from women following acute and chronic marijuana smoking. These samples (N = 1350) are aliquots of blood plasma samples which have already been analyzed for determination of levels of pituitary gonadotropins and gonadal steroid hormones and are currently stored in ultracold freezers (-70 degrees C). We propose to determine the presence, if any, of THC and THC metabolite dose-effect relationships with indices of menstrual cycle function (including luteal phase duration abnormalities), marijuana dependence and abstinence, marijuana-related abnormalities in cardiac rate and pulmonary function, marijuana-induced changes in mood states, and concordance of marijuana and alcohol use by women. Data for all of these indices have been obtained from a cohort of 105 female subjects during the first phase of this competing renewal application.
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