Non-psychotropic cannabinoids in pain management: A comprehensive review of mechanisms, clinical evidence, and therapeutic potential

Chronic pain represents a significant global health challenge, and the limitations of conventional analgesics have urged a search for alternative therapeutic strategies. Cannabinoids derived from Cannabis sativa have emerged as prominent candidates. While psychotropic cannabinoids are known for their analgesic effects, their psychoactive properties often limit their clinical utility. Consequently, interest has shifted towards non-psychotropic cannabinoids that offer potential pain relief without inducing cognitive or euphoric effects. This comprehensive review investigates the pain-modulating mechanisms of cannabinoids, encompassing interactions with the endocannabinoid system and other non-traditional pathways, and summarizes the existing preclinical and clinical evidence supporting their use in various pain states. Furthermore, it discusses the therapeutic potential, clinical considerations, significant challenges, and the need for product standardization. This review also aims to evaluate the role and prospects of non-psychotropic cannabinoids as a therapeutic option for pain management.