Objective: The use of marijuana is associated with an increased risk for preterm birth. The aim of the current study was to examine the effects of cannabidiol (CBD) on placental drug transporters BCRP and P-gp.
Methods: Transplacental transport of Glyburide (BCRP substrate) and Digoxin (P-gp substrate) were examined. Cotyledons from term, normal placentas were dually perfused for 2 hours, with [n=6] or without [n=6] CBD (15μM). Glyburide was introduced to maternal (M) and fetal (F) compartments, while Digoxin was introduced only to the maternal compartment. Digoxin concentrations and F/M ratio of Glyburide concentrations were determined at different time points during the perfusion.
Results:  F/M ratios of Glyburide concentrations at 45,60,90 and 120min. were significantly higher (by 40-60%) in the presence of CBD (control – 0.85 vs CBD – 1.28) (fig.1) and  at the same time, CBD showed no significant influence on maternal-to-fetal transport of Digoxin (fig.2).
Conclusions: Our results show that BCRP is inhibited in the human placental barrier by exposure to CBD. However, it seems that this cannabinoid lacks the same impact on P-gp function in the human perfused cotyledon. The later observation may result from the low P-gp levels in term human placenta. These findings suggest that marijuana consumption affects the defense mechanisms of the human placenta against xenobiotics. This effect could jeopardize fetal wellbeing. Moreover, the safety of drugs that are BCRP substrates (i.e. glyburide, folic acid) which are used in pregnant women is questionable during cannabis consumption.
Feinshtein Valeria.1, Ben-Zvi Zvi.1,Erez Offer.2, Eshkoli Tamar.2, Sheiner Eyal.2, Holcberg Gershon.2
1Department of Clinical Pharmacology, Faculty of Health Sciences, Ben Gurion University, Beer-Sheva, Israel.
2Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer-Sheva, Israel.