2014 Sep 5. pii: jpet.114.216648. [Epub ahead of print]
Impact of efficacy at the mu opioid receptor on antinociceptive effects of combinations of mu opioid receptor agonists and cannabinoid receptor agonists.
Maguire DR1, France CP2.
Abstract
Cannabinoid receptor agonists [e.g. Δ9-tetrahydrocannabinol (Δ9-THC)] enhance the antinociceptive effects of mu opioid receptor agonists, suggesting that combining cannabinoids with opioids would improve pain treatment. Combinations with lower efficacy agonists might be preferred and could avoid adverse effects associated with large doses; however, it is unclear whether interactions between opioids and cannabinoids vary across drugs with different efficacy. The antinociceptive effects of mu opioid receptor agonists alone and in combination with cannabinoid receptor agonists were studied in rhesus monkeys (n=4) using a warm water tail withdrawal procedure. Etorphine, fentanyl, morphine, buprenorphine, nalbuphine, Δ9-THC, and CP 55,940 each increased tail withdrawal latency. Pretreatment with doses of Δ9-THC (1.0 mg/kg) or CP 55,940 (0.032 mg/kg) that were ineffective alone shifted the fentanyl dose-effect curve leftward 20.6- and 52.9- fold, respectively, and the etorphine dose-effect curve leftward 12.4- and 19.6-fold, respectively. Δ9-THC and CP 55,940 shifted the morphine dose-effect curve leftward only 3.4- and 7.9-fold, respectively, and the buprenorphine curve only 5.4- and 4.1-fold, respectively. Neither Δ9-THC nor CP 55,940 significantly altered the effects of nalbuphine. Cannabinoid receptor agonists increase the antinociceptive potency of higher efficacy opioid receptor agonists more than lower efficacy agonists; however, because much smaller doses of each drug can be administered in combinations while achieving adequate pain relief and that other (e.g., abuse-related) effects of opioids do not appear to be enhanced by cannabinoids, these results provide additional support for combining opioids with cannabinoids to treat pain.
The American Society for Pharmacology and Experimental Therapeutics.
The American Society for Pharmacology and Experimental Therapeutics.
KEYWORDS:
analgesia; cannabinoids; drug-drug interactions; opioids
- PMID:
- 25194020
- [PubMed – as supplied by publisher]
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