EFFECTS OF DYNORPHIN A(1-13) ON OPIATE WITHDRAWAL IN HUMANS

The objectives of the current study were to determine 1) the effects o f various doses of dynorphin A (1-13) on opiate withdrawal in humans a nd 2) the safety of dynorphin at these doses. Opiate dependent subject s who had been stabilized on morphine received a single IV dose of pla cebo, 150, 500 or 1000 mu g/kg dynorphin after exhibiting spontaneous withdrawal using a randomized, double-blinded, between-subjects study design. Observer Withdrawal Scores were lower in the 150 and 1000 mu g /kg groups as compared to placebo (P < 0.05) but no significant differ ences were observed on the observer-rated Wang or Sickness Scales. Sig nificant decreases were also found for self-reported symptoms of nervo usness, runny nose, sneezing, and painful joints in the 500 mu g/kg gr oup. Significant increases in serum prolactin levels were seen after a ll dynorphin doses; however, these were not dose-related. Dynorphin A (1-13) was well tolerated and safe, with no changes in physiologic par ameters. We conclude that dynorphin a (1-13) has a modest effect in re ducing mild opiate withdrawal in humans and is well tolerated at doses up to 1000 mu g/kg.