Functional efficacy of cannabidiol in modulating the adverse effects of heroin in primates.

PROJECT SUMMARY The recent marked increase in misuse and abuse of opioids and the epidemic of opioid overdose mortality have greatly affected our society and global community. Given that non-human primate models offer the most phylogenetically appropriate evaluation of opioid receptor functions and drug effects, the goal of this proposal

is to determine the functional efficacy and selectivity of cannabidiol, a non-intoxicating constituent of cannabis, in ameliorating heroin-associated side effects in primates. Previous studies demonstrate that cannabidiol reduced reinstatement of heroin-seeking behavior specifically triggered by a prior drug-associated cue in

rodents. The proposal will further investigate the funcitional profiles of cannbidiol as compared to clinically used medications, naltrexone and buprenorphine, in modulating two major aspects of opioid-induced adverse effects, i.e., abuse liability and respiratory depression. The proposal contains two aims: 1) To determine the

functional efficacy and selectivity of cannabidiol to attenuate the abuse-related effects of heroin, and 2) To determine the functional effectiveness of cannabidiol to modulate heroin-induced respiratory depression. These non-human primate behavioral assays have been designed specifically to reflect the therapeutic

potential of the test compound along with clinically used medications for modulating opioid-assoicated abuse liability and adverse effects and assess its functional efficacy and selectivity. Our unique set of behavioral and physiological assays in awake, behaving non-human primates, in combination with the rigorious

pharmacological desgin and analysis, provides a translational relevance to advance our understanding of potential therapeutic of cannabidiol in modulating the abuse liability and adverse effects of heroin and sheds light on future clinical interventions and the treatment options for opioid abuse.