Corticotropin-releasing factor testing reveals a dose-dependent difference in methadone maintained vs control subjects

Abstract

Opiate addiction is associated with abnormalfunction of the stress-responsive hypothalamic-pituitary-adrenal(HPA) axis. In general, addiction and withdrawalare associated with abnormalHPAresponsivity as demonstrated by baseline, dexamethasone, and metyrapone testing. Following stabilization in methadone maintenance treatment, normalization of HPA axis responsivity is observed. To further investigate HPA axis function associated with heroin addiction and its treatment, saline placebo and human corticotropin-releasing factor (hCRF) were administered intravenously in two doses, one dose lower (0.5 µg/kg) and one dose higher (2.0 µg/kg) than the dose used in standard clinical diagnostics (100 µg), to 16 normal male volunteer controls (NV) and eight male stable-dose methadone-maintained former heroin addicts without ongoing drug or alcoholabuse or dependence (MM). Plasma adrenocorticotrophic hormone (ACTH) and cortisollevels were determined at serialtime points. There was no difference in hormonalmeasurements between the two groups following placebo. NV as wellas MM displayed a dose-response effect in plasma ACTH and cortisollevels. MM displayed a significantly greater increase in plasma ACTH levels than the NV following high-dose but not low-dose hCRF (p<0.05). There was no significant difference in plasma cortisollevels between the two groups following high-dose hCRF. Thus, despite earlier documented normalization of behavioralfunction and of severalmeasures of neuroendocrine function during long-term methadone maintenance, some abnormalities in HPA axis responsivity that may be a consequence of heroin exposure, orthat may have existed priorto the addiction, can persist during stable methadone treatment. © 2003 American College of Neuropsychopharmacology.