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Original Article |
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Neuropsychopharmacology (2001) 24 568-575.10.1038/sj.npp.1395630
Altered HPA Axis Responsivity to Metyrapone Testing in Methadone Maintained Former Heroin Addicts with Ongoing Cocaine Addiction
James H Schluger MD, Lisa Borg MD, Ann Ho Ph.D and Mary Jeanne Kreek MD |
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Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA
Correspondence: Dr James H Schluger, Laboratory of the Biology of Addictive Diseases, the Rockefeller University, 1230 York Avenue, New York, NY 10021-6399
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ABSTRACT
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Metyrapone testing, a provocation of hypothalamic-pituitary-adrenocortical (HPA) axis function, was performed in 39 in-patient subjects: 10 stable methadone-maintained former heroin addicts without ongoing drug or alcohol abuse or dependence (MM), eight methadone- maintained former heroin addicts without ongoing drug or alcohol abuse or dependence other than ongoing cocaine dependence (C-MM), and 21 normal volunteers (NV). Plasma adrenocorticotrophic hormone (ACTH) levels were determined in samples drawn at 9 A.M., just before administration of 2.25 g metyrapone orally and 4 and 8 hours afterward. Following metyrapone, C-MM had levels of ACTH that were significantly higher than both MM (p < .05) and NV (p < .01); whereas, MM and NV had levels that were comparable. Area under the plasma ACTH curves yielded similar results. This study documents hyper-responsivity to removal of glucocorticoid negative feedback associated with cocaine addiction, even in the setting of methadone maintenance for heroin addiction, which here and previously has been shown to be associated with normalization of HPA axis function.
Keywords: Metyrapone; Cocaine; Methadone; Addiction; ACTH; HPA axis |
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