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Psychoneuroendocrinology. 2012 Dec;37(12):1922-8. doi: 10.1016/j.psyneuen.2012.04.006. Epub 2012 May 8.

Naltrexone effects on cortisol secretion in women and men in relation to a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project.

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Behavioral Sciences Laboratories, VA Medical Center, Oklahoma City, OK 73104, USA.


Naltrexone evokes a cortisol response through its blockade of central opioid receptors on the hypothalamic-pituitary-adrenocortical axis (HPA). The magnitude of this cortisol response may be useful as a probe for central opioid activity in different groups of subjects. Accordingly, the present study examined the effect of opioid blockade on the HPA in 70 women and 58 men with (N=41) and without (N=87) a family history of alcoholism, using a randomized, placebo-controlled, double blind administration of oral naltrexone (50mg). Saliva cortisol was sampled at baseline prior to placebo or naltrexone and again every 30 min over the next 180 min. Women had significantly larger cortisol responses to naltrexone than did the men, F=6.88, p<0.0001. There were no significant differences in cortisol response between groups differing in family history of alcoholism, F=0.65, p>0.69. The present results confirm that women have much greater central opioid restraint on the HPA than men do and that this endogenous restraint is unmasked by opioid blockade. However the results provide no evidence of a differential central opioid tonus in persons with a family history of alcoholism at this dose of naltrexone. The cortisol response to naltrexone may be a useful probe for central opioid activity in women and to a lesser degree in men.

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