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Role of efficacy at the mu opioid receptor on the interactions between mu opioid receptor agonists and cannabinoid receptor agonists: antinociception and drug discrimination (658.4)
Author(s) -
Maguire David,
France Charles
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.658.4
Subject(s) - nalbuphine , etorphine , pharmacology , opioid , agonist , morphine , μ opioid receptor , cannabinoid , cannabinoid receptor agonists , potency , chemistry , opioid receptor , cannabinoid receptor , analgesic , medicine , receptor , (+) naloxone , biochemistry , in vitro
Cannabinoids such as Δ9‐tetrahydrocannabinol (THC) enhance some (analgesia) but not other (e.g., positive reinforcing) effects of mu opioid receptor agonists. Whether efficacy at the mu opioid receptor impacts those interactions is unknown. The effects of combining THC with agonists varying in efficacy at the mu opioid receptor were studied with antinociception and drug discrimination assays in rhesus monkeys. Etorphine, morphine, and nalbuphine increased tail withdrawal latency from warm water. THC increased the potency of high (etorphine) and moderate (morphine) efficacy agonists up to 16 fold but did not alter the potency of the low efficacy agonist nalbuphine. In monkeys discriminating fentanyl from saline, THC shifted the discrimination dose‐effect curves of etorphine, fentanyl, and nalbuphine rightward and downward. THC was 3‐fold more potent in attenuating the discriminative stimulus effects of the low efficacy agonist nalbuphine than those of the higher efficacy agonists etorphine and fentanyl. These data suggest the benefit of combining cannabinoids with opioids to treat pain is greatest with drugs having high efficacy at the mu opioid receptor and the subjective effects of high efficacy drugs are more difficult to disrupt than those of lower efficacy drugs. Given that other (abuse‐related) effects of opioids are not enhanced, these data support combining opioids with cannabinoids to treat pain. Grant Funding Source : Supported by NIH grants R01DA05018, K05DA017918 (CPF), T32DA031115 (DRM), and F32DA035605 (DRM).