Temporal concordance of cocaine effects on mood states and neuroendocrine hormones.
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.
Mendelson
Jack H
JH
Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, MA 02478, USA. jmendel@mclean.harvard.edu
Mello
Nancy K
NK
Sholar
Michelle B
MB
Siegel
Arthur J
AJ
Mutschler
Nicole
N
Halpern
John
J
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*
D018765:Dopamine Uptake Inhibitors; D006728:Hormones; D003687:Dehydroepiandrosterone; D000324:Adrenocorticotropic Hormone; D003042:Cocaine; D006854:Hydrocortisone; D004837:Epinephrine