Elucidating the role of ABC transporters in the placental efflux of (-)- Δ9-tetrahydrocannabinol (THC) using a cocktail of ABC transport inhibitors.

We previously showed that THC is effluxed in the perfused human placenta cotyledons, but surprisingly this efflux was not inhibited by valspodar, a P-gp and BCRP inhibitor. P-gp and BCRP have multiple binding sites, and therefore THC may be binding to a transport site not blocked by valspodar. To test this hypothesis, we perfused human placenta cotyledons with THC in the absence and presence of a cocktail of P-gp and BCRP inhibitors. The inhibitor cocktail significantly increased the unbound maternal-to-fetal THC clearance index, indicating that P-gp and/or BCRP are likely involved in determining fetal THC exposure.