title: Effects of the mixed mu/kappa opioid nalbuphine on cocaine-induced changes in subjective and cardiovascular responses in men.
abstract: Kappa opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and reduce cocaine self-administration by rhesus monkeys. We compared the cardiovascular and subjective effects of acute doses of the mu/kappa opioid nalbuphine alone (5 mg/70 kg, intravenous (i.v.)), with cocaine alone (0.2 mg/kg, i.v.), and with nalbuphine+cocaine in combination, under placebo-controlled, double-blind conditions. Subjects met American Psychiatric Association Diagnostic and Statistical Manual (DSM-IV) criteria for current cocaine abuse. Nalbuphine serum levels exceeded 50 ng/ml within 10 min after injection, and cocaine plasma levels exceeded 130 ng/ml within 4 min. Cocaine's pharmacokinetic profile did not change after concurrent nalbuphine administration. The nalbuphine+cocaine combination was safe and without synergistic effects on heart rate and systolic or diastolic blood pressure. Moreover, the addition of cocaine did not increase the subjective effects of nalbuphine. Visual Analog Scale (VAS) ratings of High, Euphoria, Stimulated, and Good Effect were equivalent after nalbuphine+cocaine and nalbuphine alone, and both were significantly higher than after cocaine alone (area under the curve analysis) (p<0.05-0.01). Peak VAS ratings of High, Stimulated, Good Effect, and Drug Effect were also significantly higher after nalbuphine+cocaine than after cocaine alone (p<0.01). Addiction Research Center Inventory (ARCI) scores were equivalent for nalbuphine+cocaine and nalbuphine alone, but the PCAG, MBG, and amphetamine scores were significantly higher after both nalbuphine+cocaine and nalbuphine alone than after cocaine alone (p<0.01-0.003). Thus, there were no additive interactions between nalbuphine and cocaine on cardiovascular, subjective, or drug level measures after acute administration.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA 02478, USA. mello@mclean.harvard.edu
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Mello
authors.forename: Jack H
authors.initials: JH
authors.lastname: Mendelson
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Sholar
authors.forename: Maria
authors.initials: M
authors.lastname: Jaszyna-Gasior
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goletiani
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Siegel
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003971:Diastole / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D009266:Nalbuphine / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D013599:Systole / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D003042:Cocaine; D009266:Nalbuphine