Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts

The present study, conducted as part of the development of a buprenorphine/naloxone combination product, was designed to evaluate the individual and combined effects of intravenously administered buprenorphine and naloxone. This in-patient trial used a randomized, double-blind, crossover design. Ten opioid-dependent male subjects were stabilized and maintained on morphine, 15 mg given intramuscularly four times daily. Then, at 48- to 72-h intervals, subjects received one of the following by intravenous injection: (1) placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2 mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects compared to placebo as assessed with the CINA scale, an instrument which utilizes subject- and observer-reported, as well as physiological parameters. The combination of buprenorphine with naloxone in a 4:1 ratio produced opioid antagonist-like effects which should limit its potential for intravenous abuse by opioid addicts.