Share Cannabidiol Exposure During Gestation Leads to Adverse Cardiac Outcomes Early in Postnatal Life in Male Rat Offspring.

Authors

Daniel B. Hardy, Western UniversityFollow
Steven R. LavioletteFollow
Kendrick Lee, Western UniversityFollow
David RC NataleFollow

Document Type

Article

Publication Date

2-2024

Journal

Cannabis and Cannabinoid Research

URL with Digital Object Identifier

https://doi.org/10.1089/can.2023.0213

Abstract

Introduction: Studies indicate that *7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to D9-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. Methods: Pregnant Wistar rats were exposed to either 3 or 30mg/kg CBD or vehicle control i.p. daily from gestational day 6 to term. Echocardiography was used to assess cardiac function in male and female offspring at postnatal day (PND) 21. Furthermore, quantitative polymerase chain reaction (qPCR), immunoblotting, and bulk RNA-sequencing (RNA-seq) were performed on PND21 offspring hearts. Results: Despite no differences in the heart-to-body weight ratio, both doses of CBD led to reduced cardiac function exclusively inmale offspring at 3 weeks of age. Underlying this, significant alterations in the expression of the endocannabinoid system (ECS; e.g., decreased cannabinoid receptor 2) were observed. In addition, bulk RNA-seq data demonstrated transcriptional pathways significantly enriched in mitochondrial function/metabolism as well as development. Conclusion: Collectively, we demonstrated for the first time that gestational exposure to CBD, a constituent perceived as safe, leads to early sex-specific postnatal cardiac deficits and alterations in the cardiac ECS in offspring.

Notes

© Kendrick Lee 2024; Published by Mary Ann Liebert, Inc.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Citation of this paper:

Lee K, Vanin S, Nashed M, Sarikahya MH, Laviolette SR, Natale DRC, Hardy DB (2024) Cannabidiol exposure during gestation leads to adverse cardiac outcomes early in postnatal life in male rat offspring, Cannabis and Cannabinoid Research X:X, 1–16, DOI: 10.1089/can.2023.0213.