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Selected Works of Daniel Hardy
Article
Gestational exposure to cannabidiol leads to glucose intolerance in 3-month-old male offspring.
Journal of Endocrinology (2023)
  • Daniel B Hardy
  • Sebastian R Vanin, Western University
  • Kendrick Lee
  • Steven R Laviolette
  • Mohammed Sarikahya
  • Edith J Arany, Dr.
  • Mina Nashed
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Abstract
Reports in North America suggest that up to 20% of young women (18-24 years) use cannabis during pregnancy. This is concerning given clinical studies indicate that maternal cannabis use is associated with fetal growth restriction (FGR) and dysglycemia in the offspring. Preclinical studies demonstrated that prenatal exposure to Δ9-tetrahydrocannabinol, the main psychoactive component of cannabis, in rat dams led to female-specific deficits in 𝞫-cell mass and glucose intolerance/insulin resistance. Yet to date, the contributions of cannabidiol (CBD), the primary non-psychoactive compound in cannabis, remains elusive. This study aimed to define the effects of in utero cannabidiol (CBD) exposure on postnatal glucose regulation. Pregnant Wistar rat dams received daily intraperitoneal (i.p.) injections of either a vehicle solution or 3 mg/kg of CBD from gestational day (GD) 6 to parturition. CBD exposure did not lead to observable changes in maternal or neonatal outcomes, however by 3 months of age male CBD-exposed offspring exhibited glucose intolerance despite no changes in pancreatic /α cell mass. Transcriptomic analysis on the livers of these CBD-exposed males revealed altered gene expression of circadian rhythm clock machinery, which is linked to systemic glucose intolerance. Alterations in hepatic developmental and metabolic processes were also observed, suggesting gestational CBD exposure has a long-lasting detrimental effect on liver health throughout life. Collectively, these results indicate that exposure to CBD alone in pregnancy may be detrimental to the metabolic health of the offspring later in life.
Keywords
  • cannabidiol,
  • pancreas,
  • glucose intolerance,
  • insulin signaling,
  • circadian rhythm
Disciplines
Publication Date
Fall October 18, 2023
DOI
10.1530/JOE-23-0173
Citation Information
Daniel B Hardy, Sebastian R Vanin, Kendrick Lee, Steven R Laviolette, et al.. "Gestational exposure to cannabidiol leads to glucose intolerance in 3-month-old male offspring." Journal of Endocrinology Vol. 260 (2023) p. e230173
Available at: http://works.bepress.com/daniel-hardy/47/