The Endocannabinoid System in Endometriosis-Associated Pain: Mechanisms, Molecular Targets, and Therapeutic Implications.

Stone A.; Veltre V.; Camp O.; Biernat M.; Abu-Soud H. · Reproductive sciences (Thousand Oaks, Calif.) · 2026

**Background & Methods** This is a comprehensive narrative review integrating preclinical and human evidence to evaluate the mechanistic basis of cannabinoid efficacy in endometriosis-associated pain. The review synthesizes findings from in vitro studies, animal models, and epidemiological evidence regarding cannabis use among women with endometriosis, a chronic gynecological disorder affecting approximately 10% of reproductive-age women. **Key Findings** • Cannabinoids suppress endometriosis-associated pain through three primary mechanisms: (1) inhibition of inflammation by reducing proinflammatory cytokine signaling and suppressing inflammatory mediator release from mast cells and peritoneal macrophages, (2) modulation of nociceptive signaling and pain sensitization via cannabinoid and non-cannabinoid receptor interactions in endometriotic lesions, and (3) antiproliferative effects that limit growth of endometriotic lesions. • Epidemiological evidence demonstrates increasing cannabis use among women with endometriosis for symptom self-management, despite limited characterization of underlying mechanisms. Current pharmacological treatments for endometriosis-associated pain (dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia) have limited efficacy and significant side effects. • The endocannabinoid system (ECS) represents a promising therapeutic target due to its established roles in pain modulation, inflammation, and immune regulation. Evidence suggests cannabinoids may address multiple pathophysiological features of endometriosis simultaneously. **Dosage & Administration** Not reported. This review does not provide specific dosing recommendations or administration routes for cannabinoid therapies. **Safety & Adverse Effects** Not reported. The review does not discuss safety profiles or adverse effects of cannabinoid treatments in endometriosis. **Evidence Quality** This is a narrative review with moderate to low evidence quality. The analysis synthesizes preclinical evidence (in vitro and animal model studies) with epidemiological observations, but lacks clinical trial data. Significant limitations include absence of randomized controlled trials in humans, reliance on animal models that may not fully translate to clinical endometriosis, and preliminary characterization of underlying mechanisms. The authors acknowledge the urgent need for clinical trials to evaluate safety and effectiveness of cannabinoid therapies, indicating the field remains largely preclinical. This review provides theoretical foundation and rationale for future clinical investigation rather than definitive clinical evidence.

More recent cannabis research