Acute cocaine responses following cocaethylene infusion.
We report results of a randomized, double-blind, placebo-controlled, within-subject study (n = 8) to determine the ability of cocaethylene to modulate acute responses to cocaine and identify significant pharmacokinetic interactions between cocaine and cocaethylene. Stable plasma cocaethylene concentrations (0, 50, or 200 ng/ml) were maintained for 840 minutes. Cocaine (0, 0.25, or 0.5 mg/kg) was injected over 1 minute after 240 minutes of cocaethylene. Blood samples, subjective, and physiological measures were collected. No differences over baseline responses were observed following 240 minutes of a steady state cocaethylene infusion for cardiovascular or subjective responses. "Rush" duration following a cocaine challenge (0.5 mg/kg) declined when administered during the course of a 200 ng/mL cocaethylene infusion. (p = 0.01). No pharmacokinetic interaction occurred when cocaine was administered in conjunction with cocaethylene. Findings indicate that continuous 8-hour exposure to cocaethylene is safe, produces acute tolerance to itself, and reduces some behavioral effects of coadministered cocaine. Agonist substitution therapy may have potential as an alternative treatment for cocaine dependence.
Virginia Commonwealth University, Richmond, Virginia, USA.
Jennifer
J
Baker
Peter
P
Jatlow
Patricia
P
Pade
Viswanathan
V
Ramakrishnan
Elinore F
EF
McCance-Katz
D000328:Adult; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000523:psychology / Q000534:rehabilitation*; D004311:Double-Blind Method; D004347:Drug Interactions; D004361:Drug Tolerance; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010919:Placebos; D016896:Treatment Outcome
D010919:Placebos; C066444:cocaethylene; D003042:Cocaine