Unraveling the Anticancer Mechanisms of Cannabidiol in Colorectal Cancer via Network Pharmacology and Molecular Docking

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and currently available treatments are often associated with notable adverse effects. Cannabidiol (CBD), a bioactive constituent of Cannabis sativa, has exhibited promising antitumor potential. However, its precise molecular mechanisms remain unclear. Therefore, this study aims to investigate the mechanism of action of cannabidiol in colorectal cancer using a network pharmacology approach supported by molecular docking analysis. This study employed an integrative framework combining network pharmacology with molecular docking. Putative targets of CBD and CRC-related genes were retrieved using Swiss Target Prediction, MalaCards, and DisGeNET databases. Protein–protein interaction (PPI) networks were constructed and examined through STRING and Cytoscape. Functional enrichment analysis was performed using ShinyGO, while gene expression patterns and immune infiltration were analyzed via UALCAN and TISIDB. A total of 95 overlapping genes between CBD-related targets and CRC-associated genes were identified. Six hub genes (ANXA5, IGF1R, JAK2, MAPK8, MDM2, and PARP1) emerged as particularly significant due to their strong network centrality and involvement in key biological processes. Molecular docking results indicated that CBD binds effectively with these targets, potentially influencing major signaling pathways such as RAS/MAPK and PI3K-AKT/FoxO, which are essential for regulating cell growth, apoptosis, and the cell cycle. Among these genes, ANXA5 and JAK2 showed strong associations with immune cell infiltration, suggesting their involvement in modulating the tumor immune microenvironment. CBD may exert multi-target regulatory effects in CRC by modulating key genes and signaling pathways, supporting its potential as an adjunct therapeutic to enhance efficacy and reduce the toxicity of conventional treatments.