Objectives. Marijuana is the most commonly used
illicit drug during pregnancy. Due to high lipophilicity,
cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of
cannabidiol (CBD), a major non-psychoactive
cannabinoid, on
P-glycoprotein (P-gp) and
Breast Cancer Resistance
Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar
choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP
protein and
mRNA levels were determined following chronic (24-72 h) exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (
calcein-AM,
DiOC2(3) and rhodamine123(rh123)).
Cyclosporine A (CsA) served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the
protein and
mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the
choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of
calcein,
DiOC2(3) and rh123) was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that
marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.