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Published on: March 29, 2018
Placental transfer and vasoactivity of cannabidiol: beware of rapid oxidation
M S Harhangi1, L Höfert2, A H J Danser3
1Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Introduction:
Cannabis use is increasing among pregnant women, although such use associates with fetal growth restriction and preeclampsia. While most research focuses on Δ9-tetrahydrocannabinol (THC), many pregnant women use cannabidiol (CBD)-containing products like CBD-oils. It is unknown whether CBD is transferred across the placenta.
Methods:
CBD transfer was studied using an ex vivo placental perfusion model, making use of healthy term placentas. CBD was added to the maternal side. Placentas were perfused for 180 min. Using liquid chromatography-tandem mass spectrometry, CBD was quantified in perfusates and post-perfusion biopsies. Vascular reactivity of CBD and THC was determined in chorionic plate arteries using wire-myography with and without antagonists for the 2 types of CB receptors (CB1 and CB2).
Results:
CBD concentrations in the maternal buffer dropped by >80% within 30 min due to rapid oxidation and remained undetectable in fetal samples. Albumin in combination with the anti-oxidant sodium ascorbate prevented this rapid drop. With albumin and sodium ascorbate being present, CBD transfer to the fetal side could be observed, reaching a fetal/maternal ratio of 0.32 ± 0.23, while 11 ± 4% was recovered in tissue. Furthermore, CBD dilated healthy placental arteries by 36 ± 4%. This was attenuated by AM251 (CB1 receptor antagonist) and AM630 (CB2 receptor antagonist). THC induced vasoconstriction in the presence of AM251.
Discussion:
Rapid oxidation of CBD can be prevented by adding an antioxidant. Under those conditions, CBD transfers to the fetus. CBD dilates fetoplacental vessels, while THC induces constriction. These data may help to understand potential risks of cannabis use in pregnancy.
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