Insights Into the Role of Cannabinoids in the Management of Endometriosis-Associated Pain [ID 3776]

Alexandra M. Stone, Vanessa L. Veltre, Olivia G. Camp, Mia M Biernat, Husam M. Abu‐Soud
In: Obstetrics & Gynecology · 2026 · vol. 147(5S) , pp. 12S · doi:10.1097/aog.0000000000006265.28 · W7160179271
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Cannabinoids may modulate endometriosis-associated pain by reducing inflammation and nociception, but human clinical trials are needed to confirm efficacy and safety.

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This review examines the potential of cannabinoids as a therapeutic target for managing pain associated with endometriosis, a chronic inflammatory condition. By analyzing preclinical data from in vitro and animal studies, the authors identify mechanisms such as reduced inflammatory mediator release and inhibition of nociceptive signaling through cannabinoid and TRPV1 receptors. The paper notes that while cannabinoids show antiproliferative effects on lesions, there is currently a significant lack of large-scale human clinical trials to validate these findings. This paper is centrally about endometriosis — specifically exploring the role of the endocannabinoid system in modulating disease progression and associated pain.

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Abstract

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.
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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.

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endometriosischronic_pelvic_pain

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