Effects of dynorphin A(1-13) on opiate withdrawal in humans.

The objectives of the current study were to determine 1) the effects of various doses of dynorphin A (1-13) on opiate withdrawal in humans and 2) the safety of dynorphin at these doses. Opiate dependent subjects who had been stabilized on morphine received a single IV dose of placebo, 150, 500 or 1000 microg/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 microg/kg groups as compared to placebo (P < 0.05) but no significant differences were observed on the observer-rated Wang or Sickness Scales. Significant decreases were also found for self-reported symptoms of nervousness, runny nose, sneezing, and painful joints in the 500 microg/kg group. Significant increases in serum prolactin levels were seen after all dynorphin doses; however, these were not dose-related. Dynorphin A (1-13) was well tolerated and safe, with no changes in physiologic parameters. We conclude that dynorphin A (1-13) has a modest effect in reducing mild opiate withdrawal in humans and is well tolerated at doses up to 1000 microg/kg.