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Research ArticleArticle

Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid μ Agonists in Healthy Volunteers

Diana J. Walker and James P. Zacny
Journal of Pharmacology and Experimental Therapeutics June 1999, 289 (3) 1454-1464;
Diana J. Walker
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James P. Zacny
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Abstract

The subjective, psychomotor, and physiological effects of three opioid μ-receptor agonists were studied in healthy volunteers using a cumulative-dosing procedure. Sixteen volunteers with no history of drug abuse received i.v. injections of saline (SAL), morphine (MOR), hydromorphone (HM), or meperidine (MEP) in a randomized double-blind crossover design. Subjects received 1 injection/h for the first 4 h, and a 3-h recovery period followed. SAL was injected first during each session, then SAL or increasing doses of each drug were administered every hour for the next 3 h. The absolute doses per injection were MOR: 2.5, 5, and 10 mg/70 kg; HM: 0.33, 0.65, and 1.3 mg/70 kg; and MEP: 17.5, 35, and 70 mg/70 kg. These injections resulted in cumulative doses of MOR: 2.5, 7.5, and 17.5; HM: 0.33, 0.98, and 2.28; and MEP: 17.5, 52.5, and 122.5 mg/70 kg. Subjects completed mood forms and psychomotor tests, and physiological measures were recorded at various times after each injection and during recovery. MEP tended to produce the most intense effects immediately after drug injection, which dissipated rapidly. MOR produced the mildest effects but was associated with unpleasant side effects during recovery and after the session. HM’s effects were stronger than MOR’s, and the recovery from HM was slower than with MEP. None of the opioids produced consistent effects that are typically associated with abuse liability. Orderly dose-response functions suggested that our cumulative-dosing procedure is an efficient way of determining dose-response functions for multiple opioids within the same subjects within the same study.

Footnotes

  • Send reprint requests to: Dr. Diana J. Walker, Ph.D., Dept. of Anesthesia and Critical Care, The University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637. E-mail:dwalker{at}airway.uchicago.edu

  • ↵1 This research was supported by National Institute on Drug Abuse Grant DA-08573. Portions of these data were presented at the 60th Annual Scientific Meeting of the College on Problems of Drug Dependence, Scottsdale, Arizona; at the 11th Annual Scientific Meeting of the Great Lakes Chapter-American Society for Pharmacology and Experimental Therapeutics, Chicago, Illinois; and at the 72nd Clinical and Scientific Congress of the International Anesthesia Research Society, Orlando, Florida.

  • Abbreviations:
    ARCI
    Addiction Research Center Inventory
    PCAG
    pentobarbital-chlorpromazine-alcohol group
    BG
    benzedrine group
    AMP
    amphetamine
    LSD
    lysergic acid diethylamide
    MBG
    morphine-benzedrine group
    VAS
    visual analog scale
    DEL
    Drug Effect/Liking
    OAC
    Opiate Adjective Checklist
    DSST
    Digit Symbol Substitution Test
    HM
    hydromorphone
    MEP
    meperidine
    MOR
    morphine
    SAL
    saline
    BL
    baseline
    • Received September 3, 1998.
    • Accepted February 13, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 3
1 Jun 1999
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Research ArticleArticle

Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid μ Agonists in Healthy Volunteers

Diana J. Walker and James P. Zacny
Journal of Pharmacology and Experimental Therapeutics June 1, 1999, 289 (3) 1454-1464;

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Research ArticleArticle

Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid μ Agonists in Healthy Volunteers

Diana J. Walker and James P. Zacny
Journal of Pharmacology and Experimental Therapeutics June 1, 1999, 289 (3) 1454-1464;
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