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.
Department of Psychiatry, University of Minnesota Hospital and Clinic, Minneapolis 55455, USA.
S
S
Specker
W
W
Wananukul
D
D
Hatsukami
K
K
Nolin
L
L
Hooke
M J
MJ
Kreek
P R
PR
Pentel
D000328:Adult; D015415:Biomarkers; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004399:Dynorphins / Q000009:adverse effects / Q000627:therapeutic use*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects; D009294:Narcotics / Q000009:adverse effects* / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D016896:Treatment Outcome
D015415:Biomarkers; D009294:Narcotics; D010446:Peptide Fragments; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine; D011388:Prolactin