Cannabis sativa and the endocannabinoid system in cervical cancer: molecular targets and mechanistic insights from preclinical models-narrative review

Abstract

Abstract Introduction Cervical cancer is among the major causes of cancer-related mortality, particularly in low- and middle-income countries where access to effective screening and treatment is limited. The endocannabinoid system (ECS), which comprises of cannabinoid receptors (CB1 and CB2), non-classical targets (TRPV1, GPR18 and GPR55), endogenous ligands, and metabolic enzymes, has emerged as a potential therapeutic target in several malignancies, including cervical cancer. Cannabis sativa (C. sativa) –derived phytocannabinoids, notably cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (Δ⁹-THC), interact with ECS components and may modulate key cancer-related pathways. This review aims to critically assess in vitro evidence on the effects of C. sativa phytochemicals in cervical cancer and to examine the underlying mechanisms associated with endocannabinoid system modulation. Methods A narrative literature search was conducted using PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar. Relevant peer-reviewed English-language studies investigating Cannabis sativa , cannabinoids, or ECS components in cervical cancer models were included. Five studies met the inclusion criteria. Only 5 studies were eligible for this study. Key findings Available in vitro evidence indicates that C. sativa extracts and phytocannabinoids exhibit cytotoxic and mechanistic effects in cervical cancer cell lines. These effects involve both ECS-dependent and independent pathways, including TRPV1 activation, modulation of MAPK signaling, induction of TIMP-1, reactive oxygen species (ROS) generation, mitochondrial dysfunction, and apoptosis. However, evidence also suggests context-dependent and potentially opposing roles of ECS signaling, including cytoprotective effects mediated by CB1/CB2 receptors. Conclusion Current evidence is limited to a small number of in vitro studies and remains insufficient to support conclusions regarding therapeutic efficacy. The observed effects are exploratory and highly context-dependent. Further research, including in vivo validation and studies in HPV-driven models, is required to determine the biological and clinical relevance of ECS modulation in cervical cancer.