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.