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Evaluation of cannabidiol effects on oxycodone-induced analgesia and reward-related behaviors in rats

Ariana Brice-Tutt
University of Florida

Co-Authors: Wendi Malphurs1, Azin Behnood-Rod1, Cassidy Kramer1, Alexandria Senetra1, Robert M. Caudle1, Marcelo Febo1, Adriaan W. Bruijnzeel1, Abhisheak Sharma1, Barry Setlow1, Niall P. Murphy1, John K. Neubert1
1University of Florida

We evaluated the effects of cannabidiol and oxycodone combinations on pain- and reward-related behavior in rats. Rats were trained to consume sweetened condensed milk solution under painful (44.5°C) and non-painful (37°C) conditions in an operant pain assay. They were then treated daily for 14 days with oxycodone (0.56 mg/kg, i.p.), cannabidiol (3.2 and 10 mg/kg, i.p.), cannabidiol + oxycodone combinations, or vehicle, and operant pain responding was evaluated. Rearing behavior was also recorded. Oxycodone alone increased operant responding under both painful and non-painful conditions. Neither dose of cannabidiol alone altered responding. Combined with oxycodone, however, cannabidiol dose-dependently increased the analgesic effect of oxycodone, but this effect was only statistically significant at the painful (44.5°C) temperature. Oxycodone also produced locomotor sensitization, which was neither attenuated nor potentiated by cannabidiol. In a separate study, rats conditioned with oxycodone in a conditioned place preference paradigm developed a significant preference for the oxycodone-paired chamber, an effect that was not impacted by combination with cannabidiol. These results suggest that while being devoid of inherent analgesic and rewarding effects, cannabidiol potentiates the analgesic effects of oxycodone without affecting its rewarding properties. As such, cannabidiol may be useful as an opioid-sparing approach to treating pain.

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