Hypersensitivity of the hypothalamic-pituitary-adrenal axis to naloxone in post-traumatic stress disorder

Naloxone, which increases endogenous corticotropin-releasing hormone (CRH) release by blocking an inhibitory opioidergic tone on the hypothalamic-pituitary-adrenal (HPA) axis, was administered in a dose-response protocol to seven healthy volunteers and 13 patients with treated posttraumatic stress disorder (PTSD). Six of the PTSD patients showed an increased hormonal response to the lowest naloxone dose (6 micrograms/kg) compared to both the control subjects and the other PTSD patients. This difference persisted on detailed subgroup analysis, although it was less marked at the highest naloxone dose (125 micrograms/kg). The responses of the other seven PTSD patients were indistinguishable from those of the control group. The greater responses of the six PTSD patients could not be explained on the basis of associated psychiatric illnesses or psychotropic drug therapy, and did not correlate with standard psychological testing or severity of PTSD. The results of this preliminary study therefore suggest that a hypersensitivity of the HPA axis to endogenous CRH stimulation may occur in PTSD.