Cocaine effects on pulsatile secretion of ACTH in men

The effects of cocaine on pulsatile secretion of adrenocorticotropic hormone (ACTH) in men were studied under controlled clinical research ward conditions. Eight men with a Diagnostic and Statistical Manual of the American Psychiatric Association Version III, revised, diagnosis of concurrent cocaine and opioid dependence provided their informed consent for participation in this study. After an overnight fast, a challenge dose of cocaine (30 mg i.v.) or placebo was administered under single-blind conditions in a randomized order on 2 study days. Blood samples were collected at 2-min intervals for 76 min during base line and for an additional 76 min after i.v. administration of the challenge dose. Peak plasma cocaine levels of 313.8 +/- 46.5 ng/ml were detected within 2 min after cocaine administration. The cluster analysis program originally described by Veldhuis and Johnson (1986) was used to characterize ACTH pulsatile secretion (Iranmanesh et al., 1990). Acute cocaine administration (30 mg i.v.) significantly increased ACTH mean peak amplitude (P < .05), mean percent increase in peak amplitude, (P < .05), mean peak area (P < .04), total peak area (P < .04) and incremental peak height (P < .04). Mean ACTH valley levels (P < .02) and mean valley nadir (P < .02) were also significantly increased after cocaine administration. We postulate that cocaine stimulates the release of corticotropin releasing factor and that the cocaine-induced secretion of corticotropin releasing factor increases the amplitude of ACTH pulses, because ACTH pulse frequency was not altered by cocaine.