Role for endocannabinoids in early pregnancy: recent advances and the effects of cannabis use

The endocannabinoid system (ECS) is associated with several physiological processes, including reproduction. This system consists of the cannabinoid receptors, endocannabinoid ligands, and enzymes that metabolize and degrade these fatty acids. Recent evidence shows that cannabinoid receptors are expressed in cells of the reproductive system, including endometrial stromal cells, ovaries, and sperm cells. Emerging and recent research suggests that the ECS may play a significant role in reproduction. The endocannabinoid ligands anandamide and 2-arachidonoylglycerol are crucial for successful endometrium decidualization, placental development, and embryo implantation. Alteration in cannabinoid receptor expression or in endocannabinoid homeostasis by excessive intake of cannabis during pregnancy is associated with negative pregnancy outcomes, including preterm birth. The use of medicinal cannabis is becoming more widespread in Western countries, especially in people of reproductive age. Cannabis contains phytocannabinoids, which modulate the ECS, and emerging evidence suggests that phytocannabinoids, through their action on cannabinoid receptors, may have a negative impact on fertility, pregnancy outcome, and fetal health. In this mini-review, we highlight the recent advances in the field, which explore the role of endocannabinoids in early pregnancy and the effects of excessive intake of phytocannabinoids in pregnancy outcomes.