Endocannabinoids are lipid messenger molecules that play a key role in our lives, promoting and maintaining homeostasis in the body.
Their role is so important that they influence every single stage of human development, from conception to the implantation of the embryo, from birth to the first days of life.
What do endocannabinoids have to do with sex?
Anandamide (AEA) and 2-arachidonoylglycerol (2-AG), the main endocannabinoids deliver their message by binding to cannabinoid receptors (CB1 and CB2 first) to be then degraded by enzymes (FAAH, MAGL, etc. …) or recycled by the cell.
Recently, studies have been conducted in mice to understand the role of endocannabinoids in relation to male sexual behavior.
These studies have shown that administration of the endocannabinoid AEA, stimulates sexual activity in males with copulation difficulties, while also reducing ejaculation thresholds in sexually apathetic subjects.
These effects of AEA are mediated by CB1 receptor activation and are also seen in healthy mice.
Furthermore, the action of this endocannabinoid varies greatly with respect to dosages, sometimes causing even opposite effects.
How the Endocannabinoid System regulates fertility in men
Both CB1 and CB2 receptors are receptors of the Endocannabinoid System (Endocannabinoid System, ECS) present in the spermatozoa.
Anandamide level is critical for controlling the percentage of living and motile sperm (viability and motility), modulating energy expenditure, and controlling the number of testosterone-producing cells (also called Leydig cells).
These functions are controlled by the CB1 receptor, while CB2 receptor activation is responsible for initiatingsperm production and regulating the speed of sperm movement.
How the Endocannabinoid System (ECS) regulates the female reproductive system
Virtually every event inherent in the female reproductive system is affected by one or more elements of the ECS, a fully active and functioning system in the cells and tissues of the female reproductive organs.
Both AEA and 2-AG have been identified in the uterus, and proper regulation of their levels is essential for successful embryonic passage through the oviduct and implantation in the uterus.
This process occurs through enzymatic degradation by FAAH and MAGL of the two endocannabinoids (AEA and 2-AG) at crucial times for embryonic development and implantation.
As research shows, the role of these enzymes is critical and they may even provide a new diagnostic tool. In fact, women subjected to spontaneous miscarriages have reported low levels of the FAAH enzyme when compared with women who successfully carried a pregnancy.
How the Endocannabinoid System regulates fetal development
CB1 receptors also play a crucial role infetal brain formation. These receptors are in fact responsible for the differentiation of neuronal progenitor cells into neurons or glial cells.
CB1s also act as “guides” for connections between neuronal cell extensions (axons), indicating the right path to follow and where to make connections with other cells.
How Cannabinoid Receptors Control Delivery
Several recent data suggest that the Endocannabinoid System plays a crucial role in a multitude of birth-related events, and that alterations in the CB1 signal pathway are linked to premature births. In fact, Wang’s group in 2008 showed that a defect in the CB1 receptor signaling pathway is capable of altering normal progesterone and estrogen levels, with consequent effects on the duration of pregnancy.
CB1 receptors are also involved with labor, as they appear to alter and coordinate the endocrine axis of corticotropin-releasing hormone, a substance that is released at high levels close to delivery, as a trigger signal to terminate the pregnancy.
How the ECS regulates the baby’s appetite and breastfeeding
Once we leave the comfort of the womb, endocannabiodes still continue to be very important for the survival of the newborn.
In fact, it has been discovered that endocannabinoids, oxylipins and other similar compounds are present in mother’s milk, and that 2-AG, the most abundant endocannabinoid in human milk, is critical for stimulating appetite in infants and aiding them in lactation.
Studies in mice have revealed the crucial role of 2-AG for the properinnervation of the tongue muscles of the young and the concomitant appetite stimulation induced by binding of 2-AG to CB1 receptors.
When the researchers “blocked” the CB1 receptors with an antagonist – a molecule that instead of activating the receptors prevents them from functioning – the pups’ growth stopped, leading to their death within a week. The simple co-administration of Tetrahydrocannabinol (THC) in the puppies, reactivating the CB1 cannabinoid receptors, almost completely reversed the effects of the antagonist drug, and the puppies returned to growth.
Endocannabinoids cover a key role in all stages of the reproductive cycle. A deficiency of these can result in even severe effects on fertility and infant survival. Further studies are needed to clarify whether and how phytocannabinoids may prove useful for couples undergoing conception.