Effects of infusion rate of intravenously administered morphine on physiological, psychomotor, and self-reported measures in humans

Although the rate of onset of a drug effect is commonly believed to contrib ute to a drug's abuse liability, only a few systematic experimental studies have been conducted examining this notion. The present study determined th e profile of physiological, psychomotor, and self-reported effects of infus ion rate (a key means of manipulating onset of drug action) of intravenousl y administered morphine, the prototypical analgesic with a known abuse liab ility 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 health y volunteers under three infusion rates (2 min bolus, 15 min, and 60 min). Faster infusions of morphine produced greater positive subjective effects t han slower infusions on visual analog scale measures of good drug effect, d rug liking, and high. Faster infusions also resulted in greater self-report ed drug effects and opioid agonist effects, without producing significant p hysiological or psychomotor impairment. Importantly, faster rates of drug i nfusion produced significantly higher morphine plasma levels than slower ra tes, and morphine plasma levels followed a similar pattern and timing of pe ak effect as the self-reported effects of the drug. Moreover, morphine prod uced 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 an d the rate of at which it is administered may function to jointly affect th e abuse liability of the drug.