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Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat.

Abstract

We have shown in past isobolographic studies that a small amount of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) can enhance morphine antinociception in mice. However, previous studies of the Delta(9)-THC/morphine interaction were performed using normal mice or rats and evaluated acute thermal antinociception. Less is known about cannabinoid and opioid interactions involved in mechanical nociception and in chronic inflammatory pain models, such as Freund's complete adjuvant-induced arthritic model. One fixed-ratio combination was chosen for testing the interaction between Delta(9)-THC and morphine in the Freund's adjuvant-induced arthritic model. This combination represented a 1:1 ratio of the drugs and thus consisted of equieffective doses ranging from 0.1 to 5 mg/kg Delta(9)-THC and from 0.1 to 5 mg/kg morphine. The combination ED(50) value for the fixed ratios (total dose) in relation to the ED(50) value of the drugs alone was determined. The isobolographic analysis indicated a synergistic interaction between Delta(9)-THC and morphine in both the non-arthritic and the arthritic rats. Since Freund's adjuvant-induced alteration in endogenous opioid tone has been previously shown, our data indicate that such changes did not preclude the use of Delta(9)-THC and morphine in combination. As with acute preclinical pain models in which the Delta(9)-THC/morphine combination results in less tolerance development, the implication of the study for chronic pain conditions is discussed.

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  • Publisher Full Text
  • Authors

    Cox ML, Haller VL, Welch SP

    Source

    European journal of pharmacology 567:1-2 2007 Jul 12 pg 125-30

    MeSH

    Analgesics, Non-Narcotic
    Animals
    Arthritis, Experimental
    Dose-Response Relationship, Drug
    Dronabinol
    Drug Synergism
    Drug Therapy, Combination
    Male
    Morphine
    Narcotics
    Pain Threshold
    Physical Stimulation
    Pressure
    Rats
    Rats, Sprague-Dawley

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    17498686