¹Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA, USA

Correspondence: Dr NK Mello, Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. Tel: +1 617 855 2716; Fax: +1 617 855 2519; E-mail: mello@mclean.harvard.edu

Received 13 April 2004; Revised 27 October 2004; Accepted 29 October 2004; Published online 15 December 2004.

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.