Acute physical dependence: Time course and relation to human plasma morphine concentrations

摘要: Objectives To characterize the postmorphine time course of precipitated withdrawal responses in comparison with opioid agonist effects and plasma morphine concentrations. Background The study provides a more detailed comprehensive assessment postagonist acute dependence humans than previously available. Design Opioid effects, levels, by naloxone (10 mg/70 kg, administered intramuscularly) were examined at 1, 3, 6, 12, 18, 24, 30, 36, 42 hours after single dose (18 10 nondependent opioid-experienced subjects. Results The intensity subjectively reported was greatest when testing conducted 6 administration, whereas peak (pupil constriction subjective ratings) highest concentrations (57.3 ng/ml) observed shortest test interval (1 hour) morphine. Offset naloxone-precipitated differed across specific measures, hot cold feelings elevated for longest (36 hrs), but significant generally apparent up to 24 pretreatment. Agonist lasted through only 12 hours; trace amounts detected 30 administration. Conclusions Results show that physical engendered peaks later persists over longer duration administration do other effects. This suggests neuronal adaptations underlying develop decay gradually during episode receptor occupancy. The presence detectable is consistent competitive displacement mechanism although noncompetitive actions or its metabolites are not ruled out. Clinical Pharmacology & Therapeutics (1995) 57, 270–280; doi: