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 μg/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 μg/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 μg/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 μg/kg.
Bibliographical noteFunding Information:
Acknowledgements The authors wish to acknowledge Margaret Porter, BA, Neil Maniar, BA, and Mithat Gundez, MA for the measurement of prolactin levels. This study was supported by PHS grants DA08067m DA01530, DA00049, DA09259 and Clinical Research Center Grant MO1 RR00400 (National Center of Research Resources).
- Opiate withdrawal