Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain

Abstract

Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment. Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development. Here we evaluate the effects of repeated exposure to {Delta}9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis. In this model, female mice develop pelvic mechanical hypersensitivity, anxiety-like behavior and sharp memory deficits associated to the presence of extrauterine endometrial cysts. Interestingly, chronic THC (2 mg/kg/day) provides sustained alleviation of pelvic hypersensitivity without altering the anxiogenic phenotype, modifies uterine innervation and restores cognitive function, an effect correlated with neuroinflammatory changes in prefrontal cortex. Strikingly, THC also inhibits the development of endometrial cysts. These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.