576. UNDERSTANDING THE IMPACT OF ACUTE AND CHRONIC OPIOID EXPOSURE ON ENDOCANNABINOID FUNCTION AND STRESS SENSITIVITY IN HUMANS

Abstract Background The endocannabinoid (eCB) system is a neuromodulatory system that plays a significant role across a variety of behaviors critical to health and well-being, including stress reactivity, reward processing, and social interaction. While it is appreciated how exogenous cannabinoid administration (e.g., cannabis use) can impact this system, recent work has shown that the eCB system is impacted by acute and chronic use of other drug classes, as well. The eCB system has a rich pharmacology that allows for multiple methods of targeting, apart from direct receptor binding. Thus, understanding how acute and chronic drug exposure impacts eCB function and related behaviors may highlight novel pharmacotherapeutic opportunities. Aims & Objectives Our goal is to explore how acute and chronic opioid exposure impacts the eCB system and related behaviors. Method In a series of studies, we have collected blood samples to assess peripheral levels of eCB system ligands and will relate these to opioid exposure and stress sensitivity. First, we will highlight recently published data in healthy adults and chronic, non-medical opioid users, highlighting differences in circulating eCB levels that relate to feelings of social exclusion. Next, we will provide data from a double-blind, within-subject, placebo-controlled oxycodone administration study in healthy adults exposed to a social stressor, showing striking gender differences. Results Broadly, our result suggest a critical link between opioid-induced changes in eCB function and stress sensitivity. Chronic opioid exposure impacts concentrations of eCB ligands, which relates to feelings of social exclusion. Ongoing analyses are currently whether this relationship exists following acute opioid administration. Moreover, we will briefly compare these effects to recent work exploring similar impacts of alcohol and stimulant exposure in humans, profiling the shared and unique ways in which the eCB system is impacted by substance us and may subsequently contribute to long-term dysregulation of stress processing. Discussion & Conclusions Together, this work will highlight the eCB system as a critical target mediating stress and substance use in humans, suggesting novel therapeutic opportunities for substance use disorders, including opioid use disorder.