title: Temporal concordance of cocaine effects on mood states and neuroendocrine hormones.
abstract: 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.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, MA 02478, USA. jmendel@mclean.harvard.edu
authors.forename: Jack H
authors.initials: JH
authors.lastname: Mendelson
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Sholar
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Siegel
authors.forename: Nicole
authors.initials: N
authors.lastname: Mutschler
authors.forename: John
authors.initials: J
authors.lastname: Halpern
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000339:Affect / Q000187:drug effects*; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D003687:Dehydroepiandrosterone / Q000097:blood; D018765:Dopamine Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D005059:Euphoria / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D009490:Neurosecretory Systems / Q000187:drug effects*
chemical_list: D018765:Dopamine Uptake Inhibitors; D006728:Hormones; D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D003042:Cocaine; D006854:Hydrocortisone; D004837:Epinephrine