Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 819, Issue -, Pages 217-224Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2017.11.038
Keywords
Antinociception; Thermal nociception; Cannabinoid receptor agonist; mu opioid receptor agonist; Drug-drug interactions; Rats
Categories
Funding
- United States National Institute on Drug Abuse [K05DA17918]
- National Institutes of Health [K05DA17918]
- Welch Foundation [AQ-0039]
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Pain is a significant clinical problem, and there is a need for effective pharmacotherapies with fewer adverse effects than currently available drugs (e.g., mu opioid receptor agonists). Cannabinoid receptor agonists enhance the antinociceptive effects of mu opioid receptor agonists, but it remains unclear which drugs and in what proportion will yield the most effective and safest treatments. The antinociceptive effects of the mu opioid receptor agonists etorphine and morphine alone and in combination with the cannabinoid receptor agonists Delta(THC)-T-9 and CP55940 were studied in male Sprague-Dawley rats (n = 16) using a warm water tail withdrawal procedure. The ratio of opioid to cannabinoid (3: 1, 1: 1, and 1: 3) varied for each mixture. Drugs administered alone or as pairwise mixtures of an opioid and a cannabinoid dose-dependently increased tail withdrawal latency. Mixtures with morphine produced supra-additive (CP55940) and additive (Delta(9)-THC) effects, whereas mixtures with etorphine and either cannabinoid were sub-additive. The interactions were not different among ratios for a particular mixture. The nature of the interaction between opioids and cannabinoids with regard to antinociceptive effects varies with the particular drugs in the mixture, which can have implications for designing combination therapies for pain.
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