The effect of the phytocannabinoid CBD during the maternal phase: Implications for female emotionality and offspring development in LG/J mice

• Grant number: 24/21828-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Andréa Cristina Peripato
• Grantee: Enzo Miassi
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa, widely used therapeutically for various conditions, such as mood disorders, epilepsy, and as an antiemetic agent. Although it is considered safe for general use, its administration during pregnancy raises concerns due to the lack of studies evaluating long-term effects on maternal emotionality and offspring development. The gradual modification of policies regulating the use of cannabis derivatives and the perception of low risk of CBD use among hyperemetic pregnant women make it essential to investigate its impacts, particularly with regard to maternal emotionality, maternal care, and associated epigenetic changes. To achieve these aims, the present study will use pregnant female LG/J mice, divided into two groups: the group exposed to CBD (20 mg/kg of CBD diluted in oil; n=20) and the control group (oil; n=20). After the mating period and the removal of males, the vehicle containing or not containing CBD will be administered orally for seven consecutive days. Emotionality will be assessed using the Open Field, Elevated Plus Maze, and Forced Swim tests at two time points: before mating and immediately following the completion of vehicle administration. Following birth, maternal care will be evaluated by observing litter size, aggressive behavior toward intruders, and the rescue test, which monitors mother-pup interactions. The pups will be monitored for weight and growth differences until adulthood. Additionally, the maternal hypothalamus will be investigated through gene expression analysis and DNA methylation of candidate genes associated with the mechanisms related to nausea and emotional responses. Thus, this study aims to contribute to the understanding of cannabidiol safety for both the mother and offspring development, providing a biological basis that supports potential outcomes in humans.