INTRODUCTION: Endometriosis is a chronic inflammatory gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, leading to debilitating chronic pain. Despite its significant effect on women’s quality of life, there remains an unmet clinical need for effective pain management strategies for endometriosis-associated pain. In recent years, the endocannabinoid system has emerged as a potential therapeutic target for endometriosis-related pain, owing to its anti-inflammatory, antinociceptive, and analgesic properties. This review aims to provide an overview of the potential mechanisms of action by which cannabinoids may modulate endometriosis, and discuss possible therapeutic applications for endometriosis-associated pain. METHODS: An extensive literature review was conducted using the online database PubMed up to March 2025, with keywords including “endometriosis,” “chronic pelvic pain,” “endocannabinoid system,” “cannabinoids,” and “cannabis.” We included observational studies in humans, as well as experiments in vitro or in animal models. RESULTS: Preclinical evidence suggests that cannabinoids modulate endometriosis-associated pain by reducing inflammatory mediator release, inhibiting nociceptive signaling by acting on cannabinoid, TRPV1, and PPAR-γ receptors in endometriotic lesions, and modulating neuroinflammation and central sensitization. Cannabinoids also exert antiproliferative and proapoptotic effects on endometriotic lesions, potentially limiting disease progression. CONCLUSIONS/IMPLICATIONS: While preclinical studies demonstrate the potential of cannabinoids as a novel therapeutic option for endometriosis-associated pain, there is a lack of large-scale, rigorous human clinical trials to support their use. Clinical trials investigating the long-term safety and efficacy of cannabinoids, particularly among women of reproductive age, are urgently needed to establish the effectiveness of cannabis in endometriosis.
Stone et al. (Thu,) studied this question.