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(1) Δ1-Tetrahydrocannabinol (Δ1-THC), the major psychoactive ingredient of cannabis, prevents ovulation when administered at 14:00 hr to pro-oestrous rats ( ed 50 = 0.98 mg/kg) . Δ6-Tetrahydrocannabinol (Δ6-THC), a psychoactive isomer of Δ1-THC, was a less potent inhibitor of ovulation ( ed 50 = 3.76 mg/kg) . However, the potent psychoactive 5′-(1″,2″ dimethylheptyl) (DMH) homologue of Δ6-THC (Δ6-THC-DMH) had a 60-fold higher ovulation-blocking potency ( ed 50 = 0.064 mg/kg) than the parent compound and about 15 times higher potency than Δ1-THC. Moreover, the action of Δ6-THC-DMH was more prolonged than that of Δ1-THC, being expressed even when the compound was administered at 08:00 hr on the day of pro-oestrus, i.e. 6 hr before the critical period for neural triggering of ovulation. (2) (+) Cannabidiol [(+)CBD] was only weakly active as an ovulation blocker and 5,6-dihydro-7-hydroxy-2-isopropyl-5-methyl-9-pentyl-2,6-methano-2H-1-benzoxocin-4(3H)-one (C5 methyl equatorial) (compound 2a) and 5,6-dihydro-7-hydroxy-2-isopropyl-5-methyl-9-pentyl-2,6-methano-2H-1-benzoxocin-4(3H)-one (C5 methyl axial) (compound 3a) were inactive, but substitution of a DMH side chain for the amyl side chain of these three compounds resulted in significant enhancement of ovulation-inhibiting activity. (−)CBD and its DMH homologue did not affect ovulation in pro-oestrous rats. (3) (+) CBD-DMH (which showed ovulation inhibiting activity in the rat) has been found to be devoid of psychotropic activity when tested in rhesus monkeys (10 mg/kg). Apparently a separation between psychotropic and hormonal activity in the cannabinoids is possible.

Poor surgical results are obtained when operating on large prolactinomas, especially when an extrasellar growth is demonstrated. Several groups have reported tumor regression following bromocriptine treatment. A case report is presented of a young hyperprolactinemic man with a large pituitary adenoma with suprasellar extension, normal visual fields, decreased libido, impotence, hypogonadism and azoospermia. This man was treated with high doses of bromocriptine for a period of 5 months. A significant improvement of potency libido and sperm concentration associated with radiological evidence of a marked reduction of tumor size was noted following suppressive treatment with this ergot alkaloid.

delta 1-Tetrahydrocannabinol (delta 1-TCH), the major psychoactive constituent of marihuana, was found to suppress the preovulatory surge of gonadotropins and thereby to prevent ovulation in rats, rabbits and rhesus monkeys. These studies suggested that the drug acts primarily on the hypothalamus to suppress luteinizing hormone releasing hormone (LHRH) secretion. The aim of the present study was to examine the direct effect of delta 1-THC, the psychoactive constituent of marihuana and cannabidiol (CBD), one of its nonpsychoactive constituents, on preovulatory rat follicles in vitro. Both cannabinoids inhibited follicular steroidogenesis in a dose-dependent manner. Basal accumulation of progesterone (P), testosterone (T) and estradiol-17 beta (E2) was reduced up to 60% by the highest doses examined (100-200 microM). The luteinizing hormone (LH)-stimulated increase in P and T was inhibited by 75-88% by the highest doses of both cannabinoids (50-200 microM), while E2, accumulation was inhibited by only 40%. It appears that the inhibitory action of cannabinoids is exerted beyond LH binding and activation of adenylate cyclase and prior to pregnenolone formation in the gonadal steroidogenic pathway. In addition to this anti-steroidogenic effect, both cannabinoids induced resumption of meiosis in follicle-enclosed oocytes cultured in hormone-free medium; 200 microM delta 1-THC resulted in 80% maturation and CBD in 75%. It seems that the action of cannabinoids on rat follicles in vitro is unrelated to their psychotropic activity.