The Clinical Significance of Endocannabinoids in Endometriosis Pain Management

Endometriosis occurs when the endometrial tissue, which normally lines the inside of a woman’s uterus, grows outside of the uterus – in the ovaries, fallopian tubes, and the membrane lining the pelvis for instance. This disorder affects approximately 5 – 15% of all women of reproductive age. Among its predominant clinical features is pain, as patients often suffer from diffuse, poorly localized severe pain. Although the pathogenesis of endometriosis largely remains unclear, the endocannabinoid system (ECS) has recently been shown to play a key role in its development, maintenance, and pain mechanism.

The ECS consists of endogenous cannabinoids – lipid molecules serving signalling functions, cell-surface receptors CB1 and CB2 that they bind to, and enzymes that synthesize and degrade them. Two major endogenous cannabinoids are anandamide and 2-AG, and two known receptors include CB1 and CB2.

Research studies have demonstrated that women with endometriosis have lower levels of CB1 receptors in endometrial tissues compared to those without. Meanwhile, the level of endogenous cannabinoids in the plasma of patients are elevated above the normal level in healthy women. The plasmatic level of anandamide and 2-AG are also found to be highly correlated with moderate-to-severe dysmenorrhea (abnormal menstrual cramps) and with moderate-to-severe dyspareunia (painful intercourse) – most common forms of endometriosis-associated pain. In other words, imbalances in the ECS function have been suggested to lead to growth of endometriosis tissue and a more severe pain experience.


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