Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Physiology and Pharmacology

Collaborative Specialization

Developmental Biology

Supervisor

Feng, Qingping

Abstract

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted in heart abnormalities in 73% of offspring with non-compaction of the myocardium and hypoplastic coronary arteries as the two main phenotypes. To our knowledge, this is the first reported study demonstrating that phytocannabinoids can induce congenital heart abnormalities. Cannabis consumption in human pregnancies could be teratogenic and should be avoided.

Summary for Lay Audience

Due to cannabis legalization, cannabis consumption has been rising, including in pregnant women. Within cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two main active ingredients, which can be consumed for either recreational or purported medicinal purposes, for example, to combat morning sickness. Despite little research inquiring about the harm THC and CBD can cause during pregnancy, as many as one in five pregnant women have consumed cannabis during pregnancy. In this thesis, a mouse model was used to determine if exposure to THC or CBD during pregnancy would induce heart defects present at birth. Oral, daily THC consumption during gestation resulted in approximately 70% of offspring having heart abnormalities. Three main observations were seen: thickened heart valves, thickened heart muscle walls, and fewer heart blood vessels. Twenty-one days after birth, heart function was also negatively impacted. Altered expression of important gene regulators and processes of heart development were implicated in contributing to the development of the CHDs. In addition, oral, daily CBD exposure during gestation resulted in approximately 70% of offspring having heart abnormalities. Two main observations were observed: failure of the heart muscle wall to compact resulting in a loose, immature heart muscle wall, and fewer coronary blood vessels that provide blood to the heart. This is the first report of THC and CBD inducing heart abnormalities. Current human research is insufficient to indicate if THC and CBD does or does not increase the likelihood of heart defects at birth. Based on this thesis and lack of human studies, cannabinoids should not be consumed during pregnancy.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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