Associations Among Endocannabinoids, Mental Health, and Obstetric Outcomes in a Pregnancy Cohort: A Preliminary Study

Abstract

Objective: Endocannabinoids, naturally occurring lipid (fat-based) signaling molecules, play a critical role in fetal development and help regulate pregnancy maintenance, placental functioning, and the timing of labor. In pregnant women, endocannabinoids are found throughout the bloodstream (circulating endocannabinoids) and in the placenta. Elevated concentrations in both blood and placenta have been linked to premature birth in high-risk cohorts. Circulating endocannabinoids have also been associated with depressive symptoms in non-pregnant cohorts. However, little is known about endocannabinoid concentrations in lower-risk pregnancies, their relationship to obstetric outcomes, and their association with maternal depressive symptoms during pregnancy. Method: This prospective study recruited 26 pregnant women (29.31 ± 6.36 years) during the first trimester. Participants self-reported depressive symptom severity each trimester using the Center for Epidemiological Studies-Depression Scale. Third-trimester maternal blood and post-delivery placental biopsies were collected to measure two key endocannabinoids: N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), using liquid chromatography-tandem mass spectrometry. Adverse obstetric outcomes were assessed postpartum. Results: Higher maternal depressive symptoms in the second trimester were associated with lower third trimester 2-AG concentrations, t(10) = 2.295, p = .045, a relationship not observed in other trimesters. Additionally, higher placental AEA concentrations were linked to greater risk of adverse obstetric outcomes, r = .415, p = .049. Conclusions: These preliminary findings suggest that endocannabinoids during pregnancy are linked to obstetric outcomes and maternal mental health, even within a lower-risk cohort. This extends prior work in non-pregnant populations and highlights the need for further study.