Ketoconazole attenuates the cortisol response but not the subjective effects of smoked cocaine in humans

Attenuation of hypothalamo-pituitary-adrenal (HPA) function in laboratory rodents has been found to reduce the reinforcing effects of cocaine. To examine whether attenuation of HPA function reduces the effects of cocaine in humans, one female and seven male 'crack' cocaine abusers were pre...

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Published inBehavioural pharmacology Vol. 9; no. 7; p. 577
Main Authors Ward, A S, Collins, E D, Haney, M, Foltin, R W, Fischman, M W
Format Journal Article
LanguageEnglish
Published England 01.11.1998
Subjects
Administration, Inhalation
Adrenocorticotropic Hormone - blood
Adult
Blood Pressure - drug effects
Cocaine - pharmacology
Dose-Response Relationship, Drug
Female
Heart Rate - drug effects
Humans
Hydrocortisone - blood
Ketoconazole - pharmacology
Male
Regression Analysis
Reinforcement (Psychology)
Surveys and Questionnaires
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Summary:Attenuation of hypothalamo-pituitary-adrenal (HPA) function in laboratory rodents has been found to reduce the reinforcing effects of cocaine. To examine whether attenuation of HPA function reduces the effects of cocaine in humans, one female and seven male 'crack' cocaine abusers were pretreated with three doses of ketoconazole (0, 600, 1200 mg), an inhibitor of adrenocorticoid biosynthesis, 1 h before receiving cocaine. Three doses of smoked cocaine (0, 12, 50 mg) were administered in counterbalanced order under each ketoconazole condition. Ketoconazole dose-dependently reduced cocaine-induced cortisol, but not adrenocorticotropin (ACTH) release, and attenuated the cocaine-induced increase in heart rate and blood pressure. Plasma ACTH levels were more predictive of blood pressure changes than either cocaine or cortisol levels. Suppression of cortisol secretion was not associated with a reduction in ratings of the subjective effects of cocaine. These results support a role for the HPA axis in the cardiovascular effects of cocaine, but do not support a role for the HPA axis in the subjective effects of cocaine. To the extent that self-administration can be predicted by subjective effects, these results further argue that the HPA axis does not play a critical role in cocaine self-administration by humans.
ISSN:0955-8810
DOI:10.1097/00008877-199811000-00013