The endocannabinoid system: A novel player in human placentation

Cannabis sativa is the most consumed illegal drug around the world. Its consumption during pregnancy is associated with gestational complications, particularly with fetal growth restriction. Endocannabinoids (eCBs) are lipid molecules that act by activating the G-protein coupled cannabinoid receptors, which are also target of the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC). The endocannabinoid system (ECS) participates in distinct biological processes, including pain, inflammation, neuroprotection, and several reproductive events. In addition, an abnormal expression of ECS is associated with infertility and miscarriages. This manuscript will review and discuss the expression of ECS in normal and pathological human placentas, and the role of eCBs and THC in trophoblast proliferation, apoptosis, differentiation, and function. The current evidence points towards a role of ECS in human placentation, shedding light on the contribution of the eCBs in the coordination of human placentation, and in the cellular mechanisms underlying the deleterious effects of cannabis consumption during pregnancy.