Objectives/Goals: The endocannabinoid (eCB) system is integral to pain perception and may have antinociceptive effects. This study is the first to examine sex differences in eCB levels and their associations with pain and risk factors that may contribute to the development or exacerbation of pain symptoms, such as sleep disturbances. Methods/Study Population: Data were analyzed from the Adolescent Brain Cognitive Development StudySM, which included a substudy to measure circulating blood eCB concentrations in a subset of participants (n=403, mean age=12.56±1.05 years, 46.4% female). Covariates included age, race and ethnicity, puberty, sex, BMI, fasting state, and recent exercise. Pain was assessed on day of the blood draw (0–10 scale), and sleep disturbances were measured by the number of nighttime awakenings. Five eCB and eCB-like molecules were examined: anandamide (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and 2-oleoylglycerol (2-OG). Results/Anticipated Results: There was a significant sex difference in 2-AG concentrations (β=-5.36, CI -8.53–2.18, p-adj=0.005), with female youth having lower concentrations than males. Because of this sex difference, all other analyses were sex-stratified. There was no association between pain on the day of the blood draw and eCB concentrations in either sex. Male youth alone exhibited a positive correlation between nighttime awakenings and concentrations of AEA (β=0.62, CI 0.26–0.99, p =0.001) and OEA (β=0.14, CI 0.065–0.21, p<0.001). Discussion/Significance of Impact: These findings suggest there may be sex-specific relationships with the eCB system and risk factors for pain. Future analyses will leverage longitudinal eCB measurements and examine how changes in eCB may relate to pain and sleep problems during adolescence.
Evanski et al. (2026) studied this question.