An Opioid/Cannabinoid Analgesic that Boosts Pain Relief and Blocks Opiate Reward

Project Summary Abuse of prescription opioids and fatalities related to their misuse have increased sharply in recent yearsmaking the development of pain medications with reduced abuse potential a major public health priorityWhen combinedopioids and cannabinoidCBreceptor agonists show analgesic effects appear to be at least additive in a number of pain modelsCannabidiolCBDalthough much less psychoactive thantetrahydrocannabinolTHCthe primary active principle in Cannabisstill retains analgesic effectsEfforts to develop analogs of CBD with improved solubility and bioavailability resulted in discovery of CBD valinate hemisuccinateCBD VHSwhich gives excellent performance in its own right in pain modelsbut also reduces the rewarding effects of morphine in a conditioned place preference testThe next stepsaddressed in this projectare to carefully delineate the effects of CBD VHS in combination with the commonly used opioid therapeutic oxycodonein order to understand their analgesic interactions and the abuse liability of the combinationsThis will be done by using drug self administration tests and analgesia models to find out whether mixture ratios that are less reinforcing still produce good pain reliefThese goals will be achieved by first giving oxycodoneOXYby the intravenous routeestablishing dose responses to OXY alonethen giving CBD VHS in various doses and see how this affects responses to OXYOnce appropriate dose ratios are selectedthen the combination will be evaluated for its ability to relieve painValidated isobolographic and dose addition analyses will be used to determine if the combinations are additive or interactivei esupraor infra additivein analgesic effectThe outcome of this Phase I effort will be the selection of the most promising fixed ratio of oxycodone and CBD VHS formulation for further preclinical development in the phase II STTRas a pain management therapeutic with minimized abuse liabilityThe Phase II development program will include characterization of the interaction in nonhuman primatespharmacokinetic and pharmacological assessments from oral formulationsand safety evaluations Project Narrative The relevance of this project to public health is especially pointed because of the current opioid addiction crisisThis proposal will advance a new cannabinoid based analgesic therapy which can allow opioid dose reduction and simultaneously reduce the reinforcing effects of oxycodoneIf successfulthis will expand the options for patients requiring chronic therapy with potent analgesicsand reduce risk of abuse overdose