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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics December 2001, 299 (3) 1056-1065;
Lisa A. Marsch
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Warren K. Bickel
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Gary J. Badger
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James P. Rathmell
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Michael D. B. Swedberg
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Bror Jonzon
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Carina Norsten-Höög
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Abstract

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.

Footnotes

  • This research was supported by AstraZeneca R&D Södertälje, Södertälje, Sweden, National Institutes of Health Grant GCRC M01 RR00109 to the General Clinical Research Center at the University of Vermont and National Institute on Drug Abuse training Grant T32DA07242. This work was presented at the 63rd Annual Meeting of the College on Problems of Drug Dependence, Scottsdale, Arizona.

  • Abbreviations:
    ARS
    adjective rating scale
    VAS
    visual analog scale
    ARCI
    Addiction Research Center Inventory
    DSST
    Digit Symbol Substitution Test
    M6G
    morphine-6-glucuronide
    M3G
    morphine-3-glucuronide
    PCAG
    pentobarbital-chlorpromazine-alcohol group
    MBG
    morphine-benzedrine group
    LSD
    lysergic acid diethylamide
    BG
    benzedrine group
    A
    amphetamine
    • Received May 9, 2001.
    • Accepted August 21, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 299 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 299, Issue 3
1 Dec 2001
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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 1056-1065;

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Research ArticleNEUROPHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics December 1, 2001, 299 (3) 1056-1065;
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