576. UNDERSTANDING THE IMPACT OF ACUTE AND CHRONIC OPIOID EXPOSURE ON ENDOCANNABINOID FUNCTION AND STRESS SENSITIVITY IN HUMANS
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".