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Utilizing a double-blind crossover design, the hormonal effects of high dose, 2 mg/kg, were compared to low dose, 0.4 mg (approx. 5 micrograms/kg), naloxone administration in physically healthy humans. A significant naloxone dose effect on plasma cortisol levels was found (p less than 0.001), but no significant effect on plasma or serum levels of prolactin, follicle stimulating hormone, luteinizing hormone, norepinephrine or epinephrine. These results confirm involvement of the endogenous opioid system (EOS) in the tonic regulation of the hypothalamicpituitary-adrenal axis, but fail to find evidence of EOS involvement in the regulation of adrenal medullary function or the gonadotrophic axis in man. The results are however consistent with a continuing action of naloxone as an EOS antagonist even at high doses in man.
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