Vol. 299, Issue 3, 1056-1065, December 2001

Effects of Infusion Rate of Intravenously Administered Morphine on Physiological, Psychomotor, and Self-Reported Measures in Humans

Lisa A. Marsch, Warren K. Bickel, Gary J. Badger, James P. Rathmell, Michael D. B. Swedberg, Bror Jonzon and Carina Norsten-Höög

Department of Psychiatry (L.A.M., W.K.B.), Department of Medical Biostatistics (G.J.B.), and Department of Anesthesiology (J.P.R.), University of Vermont, Burlington, Vermont; and AstraZeneca R&D Södertälje, Södertälje, Sweden (M.D.B.S., B.J., C.N.-H.)

Although the rate of onset of a drug effect is commonly believed to contribute to a drug's abuse liability, only a few systematic experimental studies have been conducted examining this notion. The present study determined the profile of physiological, psychomotor, and self-reported effects of infusion rate (a key means of manipulating onset of drug action) of intravenously administered morphine, the prototypical analgesic with a known abuse liability in human participants. Two doses of morphine sulfate (5 and 10 mg/70 kg, i.v.) and a placebo dose (0 mg/70 kg, i.v.) were administered to healthy volunteers under three infusion rates (2 min bolus, 15 min, and 60 min). Faster infusions of morphine produced greater positive subjective effects than slower infusions on visual analog scale measures of good drug effect, drug liking, and high. Faster infusions also resulted in greater self-reported drug effects and opioid agonist effects, without producing significant physiological or psychomotor impairment. Importantly, faster rates of drug infusion produced significantly higher morphine plasma levels than slower rates, and morphine plasma levels followed a similar pattern and timing of peak effect as the self-reported effects of the drug. Moreover, morphine produced dose-dependent increases in self-reported drug effects, opioid agonist effects, and morphine plasma levels in the study. Results suggest that the pharmacokinetic properties of a drug, including the dosage administered and the rate of at which it is administered may function to jointly affect the abuse liability of the drug.