Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease.
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 hypothalamic-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.
Brain Imaging, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.
Carlo
C
Contoreggi
Ronald I
RI
Herning
Paul
P
Na
Philip W
PW
Gold
George
G
Chrousos
Paulo J
PJ
Negro
Warren
W
Better
Jean L
JL
Cadet
D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000187:drug effects; D000328:Adult; D016022:Case-Control Studies; D015897:Comorbidity; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D003863:Depression / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000503:physiopathology*; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone