INFLUENCE OF IN UTERO CANNABIS EXPOSURE ON THE DEVELOPMENTAL PROGRAMMING OF THE GUT-BRAIN AXIS

Abstract

Cannabis use may occur during pregnancy to alleviate symptoms of nausea, anxiety, and stress. However, fetal exposure to cannabinoids, such as THC and CBD, poses potential risks to neurodevelopment and long-term health outcomes. The endocannabinoid system (ECS) is involved in neurodevelopment and gastrointestinal (GI) homeostasis and responds to exogenous cannabinoids. This study aimed to investigate both the baseline development of the ECS in the GI tract and the effects of prenatal cannabis exposure on the development of gut-brain axis components and the ECS. Samples from outbred mice were collected at a set of developmentally important time points, ranging from embryonic day 14 to postnatal day 21. The localization of cannabinoid receptor 1 (CB1) expression was examined in the fetal and postnatal small intestine, and mRNA analysis was performed to evaluate changes in gene expression. Under normal conditions, components of the ECS display developmental regulation in the GI tract. A subset of pregnant mice was exposed to cannabis smoke daily, using a strain of cannabis containing high concentrations of THC, simulating ‘real world’ cannabis use. Exposure to cannabis prenatally revealed significant changes in biometric outcomes, and in the transcription of genes associated with the ECS, ENS development, barrier function, and serotonin signaling pathways. In addition, the onset of ambulation was delayed. These findings provide valuable insights into the developmental regulation of ECS during the prenatal period and highlight the potential risks associated with prenatal cannabis exposure, particularly in terms of gut-brain axis development. Further research is required to better understand the underlying mechanisms.