Effects of dynorphin A(1–13) on opiate withdrawal in humans |
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| Authors: | S. Specker Winai Wananukul Dorothy Hatsukami Kim Nolin Lyn Hooke Mary Jeanne Kreek Paul R. Pentel |
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| Affiliation: | (1) Department of Psychiatry, Box 393 UMHC, University of Minnesota Hospital and Clinic, 420 Delaware Street S.E., Minneapolis, MN 55455, USA Fax: +1-612-626-5591, US;(2) Ramathibodi Hospital, Bangkok, Thailand, TH;(3) Department of Psychiatry, Box 392 UMHC, University of Minnesota Hospital and Clinic, 420 Delaware Street S.E., Minneapolis, MN 55455, USA, US;(4) Department of Pediatrics, Box 391 UMHC, University of Minnesota Hospital and Clinic, 420 Delaware Street S.E., Minneapolis, MN 55455, USA, US;(5) Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA, US;(6) Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA, US |
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| Abstract: | 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 1000μg/kg dynorphin after exhibiting spontaneous withdrawal using a randomized, double-blinded, between-subjects study design. Observer Withdrawal Scores were lower in the 150 and 1000μg/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 500μg/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 1000μg/kg. Received: 24 March 1997/Final version: 22 November 1997 |
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| Keywords: | Dynorphin Opiate withdrawal Human |
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