Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers

Sublingual buprenorphine is a promising new treatment for opiate dependence , but its opioid agonist effects pose a risk for parenteral abuse. A formul ation combining buprenorphine with the opiate antagonist naloxone could dis courage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged wi th IV doses of buprenorphine alone (2 mg) or in combination with naloxone i n ratios of 2 : 1, 4 : 1, and 8 : 1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdraw al and had agonist effects similar to morphine. A naloxone dose-dependent i ncrease in opiate withdrawal signs and symptoms and a decrease in opioid ag onist effects occurred after all drug combinations. Buprenorphine with nalo xone in ratios of 2 : 1 and 4 : 1 produced moderate to high increases in gl obal opiate withdrawal, bad drug effect, and sickness. These dose ratios al so decreased the pleasurable effects and estimated street value of buprenor phine, thereby suggesting a low abuse liability. The dose ratio of 8 : 1 pr oduced only mild withdrawal symptoms. Dose combinations at 2 : 1 and 4 : 1 ratios may be useful in treating opiate dependence.