Objective: To evaluate the impact of cannabidiol (CBD), the main non-psychoactive compound in marijuana, on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) expression and function in placental BeWo and Jar cells.
Study Design: Uptake of specific substrates of BCRP (Mitoxantrone) and P-gp (Calcein-AM and DiOC2(3)) was tested following acute (1h) exposure to CBD. Membranal P-gp and BCRP protein and mRNA levels were determined following chronic (24, 48 and 72h) exposure to CBD, by Western blotting and qPCR.
Results: CBD significantly inhibited BCRP dependent efflux of Mitoxantrone and P-gp dependent efflux of Calcein or DiOC2(3). Chronic exposure to CBD showed a significant decline in P-gp protein and mRNA levels, while simultaneously up-regulated BCRP protein expression and BCRP mRNA levels.
Conclusions: Placental P-gp and BCRP are inhibited functionally following acute exposure to CBD. Chronic exposure to CBD may alter P-gp and BCRP expression in the human placenta. We concluded that, recreational and routine marijuana use during pregnancy (and thus inevitable exposure to CBD) may reduce placental protective functions.
Valeria Feinshtein1, Zvi Ben-Zvi1, Boaz Sheizaf2, Eyal Sheiner2, Tamar Eshkoli2, Gershon Holcberg2.
Department of Clinical Pharmacology, Faculty of Health sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel1
Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer-Sheva, Israel, Faculty of Health sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel2