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.
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.
Authors: Megan M Moran-Santa Maria; Aimee L McRae-Clark; Sudie E Back; Stacia M DeSantis; Nathaniel L Baker; Eve G Spratt; Annie N Simpson; Kathleen T Brady Journal: Psychoneuroendocrinology Date: 2010-05-31 Impact factor: 4.905
Authors: Tara M Chaplin; Kwangik Hong; Helen C Fox; Kristen M Siedlarz; Keri Bergquist; Rajita Sinha Journal: Hum Psychopharmacol Date: 2010-07 Impact factor: 1.672
Authors: Edgar Toschi-Dias; Ivani C Trombetta; Valdo José Dias da Silva; Cristiane Maki-Nunes; Maria Janieire N N Alves; Luciana F Angelo; Felipe X Cepeda; Daniel G Martinez; Carlos Eduardo Negrão; Maria Urbana P B Rondon Journal: Eur J Appl Physiol Date: 2012-08-24 Impact factor: 3.078
Authors: Kathleen T Brady; Aimee L McRae; Megan M Moran-Santa Maria; Stacia M DeSantis; Annie N Simpson; Angela E Waldrop; Sudie E Back; Mary Jeanne Kreek Journal: Arch Gen Psychiatry Date: 2009-04