Naloxone-induced cortisol predicts mu opioid receptor binding potential in specific brain regions of healthy subjects

Gary S. Wand, Elise M. Weerts, Hiroto Kuwabara, J. James Frost, Xiaoqiang Xu, Mary E. McCaul

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Investigators have administered the opioid receptor antagonist, naloxone, to interrogate the hypothalamic-pituitary-adrenal (HPA) axis response under the assumption that this technique provides a measure of endogenous opioid activity. However it has never been tested whether provocation of the HPA axis with naloxone provides a surrogate marker for direct measurement of endogenous opioid activity using PET imaging as the gold standard. To test this hypothesis, eighteen healthy subjects underwent a PET scan with the mu-opioid receptor (MOR) selective ligand [ 11C]carfentanil (CFN). The following day ACTH and cortisol responses were assessed using a technique which allows administration of 5 incremental doses of naloxone (0, 25, 50, 100 and 250μg/kg) in a single session. Relationships between ACTH and cortisol responses and [ 11C]CFN binding potential (BP ND) were examined in 5 brain regions involved in the regulation of the HPA axis and/or regions with high concentrations of MOR. All subjects mounted graded ACTH and cortisol responses to naloxone administrations. There were significant negative relationships between cortisol response to naloxone and [ 11C]CFN BP ND in ventral striatum, putamen and caudate. When sex and smoking were added as covariates to the model, these correlations were strengthened and there was a significant correlation with the hypothalamus. There were no significant correlations between ACTH and any volumes of interest. The opioid receptor antagonist naloxone is not merely a non-specific pharmacologic activator of the HPA axis; it provides information about individual differences in opioid receptor availability.

Original languageEnglish (US)
Pages (from-to)1453-1459
Number of pages7
Issue number10
StatePublished - Nov 2011


  • Beta-endorphin
  • Cortisol
  • HPA axis
  • Mu Opioid receptors
  • Naloxone
  • PET imaging

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry


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