Abstract
Background
Preclinical data indicate a crucial role of stress in the acute effects of drugs of
abuse, maintenance of self-administration, and susceptibility to relapse. Stress system
activation may serve as a marker for a neurochemical dysfunction with prognostic significance
in patients with addiction.
Methods
We tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to ovine
corticotropin-releasing hormone (oCRH) to assess the reactivity of the hypthalamic–pituitary–adrenal
(HPA) axis in seven nonsubstance-abusing subjects, 31 polysubstance-abusing subjects
without depressive symptoms, and seven subjects with substance abuse and depressive
symptoms. No subject met diagnostic criteria for depression or other severe psychiatric
disease.
Results
Compared with normal control subjects, substance abusers showed significantly lower
ACTH and cortisol responses over the course of oCRH stimulation (p < .0001). Substance abusers with depressive symptoms showed similarly blunted responses.
Conclusions
Polysubstance abusers with no past or current diagnosis of other Axis I disorders
show blunted ACTH and cortisol responses to oCRH administration. The finding of an
activated HPA axis in this population suggests an overlapping role of central CRH
and HPA axis activation in affective disorders and substance abuse, which is likely
to constitute an endocrine milieu necessary for the maintenance of addictive behavior.
These data support the role of future therapeutic trials with nonpeptide CRH receptor
1 antagonists in these patients.
Keywords
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Article info
Publication history
Accepted:
January 10,
2003
Received in revised form:
September 30,
2002
Received:
April 11,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
