Butorphanol agonist effects and acute physical dependence in opioid abusers: comparison with morphine

This study compared the direct effects and acute physical dependence of but orphanol and morphine, opioids with differing actions at mu versus kappa re ceptors. Six non-dependent heroin-using volunteers were exposed to six cond itions in a within-subject, Latin square design using double-blind procedur es. In each session, agonist effects of single i.m. injections of butorphan ol (3 and 6 mg/70 kg), morphine (15 and 30 mg/70 kg), lorazepam (4 mg/70 kg ) or saline were evaluated. Butorphanol and morphine produced effects of co mparable magnitude on miosis and reports of 'any drug effect'. Volunteers r eported dysphoria, confusion and sedation after butorphanol, subjective eff ects that overlapped with those of lorazepam, whereas morphine produced eup horia and stimulation. Acute physical dependence (i.e, precipitated withdra wal responses to naloxone 10 mg/70 kg i.m. administered 6 h after each trea tment) significantly increased after 30 mg/70 kg morphine but not after but orphanol treatments. These differences in naloxone sensitivity are likely d ue to differences in opioid receptor (mu versus kappa) activity, affinity a nd efficacy of these compounds. Pharmacological ramifications of these resu lts are discussed. (C) 1998 Elsevier Science Ireland Ltd. All rights reserv ed.