Impact of Δ9-Tetrahydrocannabinol Administration on Measures of Oxycodone-induced Antinociception, Dependence and Reward in Mice

Oxycodone is one of the most commonly prescribed analgesics for moderate to severe pain disorders. While effective in the short term, long-term use can result in a myriad of unwanted side-effects which include tolerance, physical dependence and the development of opioid use disorder. Δ9-Tetrahydrocannabinol (Δ9-THC), is a partial cannabinoid receptor agonist which has been reported in to enhance opioid analgesia in various animal models. However, it remains unclear if Δ9-THC can modulate other aspects of repeated oxycodone intake such as tolerance and dependence. Thus, this study sought to evaluate the impact of Δ9-THC administration on measures of oxycodone-induced antinociception, dependence and reward in mice. To evaluate for thermal antinociception, dose-response curves were conducted for both oxycodone and Δ9-THC using the hotplate test. ED50’s were calculated on day 1 30 min post injection. Animals were treated twice daily with vehicle, oxycodone, THC or combination of oxycodone+THC for 5 days. On the 6th day, naloxone was administered to precipitate somatic withdrawal. Animals were video recorded and classic measures of opioid withdrawal (e.g. jumps) were evaluated using open-source pose estimation software (Deeplabcut). Δ9-THC and oxycodone alone and in combination were evaluated in the conditioned place preference assay to evaluate reward and/or aversion using doses derived from hotplate ED50 calculations. Oxycodone and Δ9-THC produced antinociceptive effects in the hotplate assay. Oxycodone produced a robust conditioned place preference, while Δ9-THC did not produce preference or aversion. Evaluations of oxycodone and Δ9-THC are currently ongoing. The results of these findings will be informative regarding the potential implementation of Δ9-THC with oxycodone in a therapeutic setting. Grant support from F32DA051160 (to RAS) R01NS042595 (RWG) R34NS126036 (RWG) Diabetes Research Center Pilot Project (AVK) Hope Center Pilot Project (to AVK) Whitehall Foundation Grant (2017-12-54 to MCC) Rita Allen Scholar Award in Pain (to MCC).