Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinical and preclinical studies, but the temporal sequence of cocaine-induced changes in other hormones and affective states is unclear. The purpose of this study was to analyze the pattern and temporal concordance of cocaine-induced changes in ACTH, cortisol, dihydroepiandrosterone (DHEA), epinephrine, heart rate and subjective reports of euphoria. Six healthy men who met Diagnostic and Statistical Manual-IV (DSM-IV) criteria for cocaine abuse provided informed consent for participation. Cocaine (0.4 mg/kg) or saline placebo was infused intravenously over 1 min under double-blind conditions. Euphoria, ACTH, epinephrine and heart rate increased significantly within 8 to 12 min after i.v. cocaine administration in all subjects (P<0.01-0.001). Moreover, the increases in euphoria, ACTH, epinephrine and heart rate each were significantly correlated with increases in plasma cocaine levels (P<0.001). Euphoria increased significantly within 2 min after i.v. cocaine injection, as plasma cocaine levels were increasing, and peak euphoria was reported at 10 min (P<0.001). Peak ACTH values were measured at 8.7 (+/-0.8) min after cocaine injection (P<0.01). Peak levels of epinephrine were measured at 10 (+/-1) min after cocaine injection (P<0.05). Peak increases in heart rate occurred at 11.7 (+/-1.1) min after cocaine injection (P<0.05). Peak levels of cortisol and DHEA were measured at 36 (+/-4.0) and 28.7 (+/-4.3) min after cocaine injection (P<0.01 and P<0.01). The temporal concordance between cocaine-induced stimulation of ACTH, epinephrine and subjective euphoria suggests that these hormonal changes are significant concomitants of the abuse-related effects of cocaine. The similarities between these hormonal profiles, the subjective effects of cocaine and the effects of "stress" are discussed.