Background: Chemotherapy-induced peripheral neuropathy (CIPN) was linked to altered metabolic pathways (Hua et al., J Pharm Biomed Anal, 2025). We conducted a prospective observational study on cancer survivors who received CBD up to 300mg/day over two months (Vigano M et al., Pharmaceuticals, 2024 & J Support Care Cancer, 2025). Untargeted metabolomics and microbiome analyses were performed on human fecal samples to identify metabolic pathways and microbiome signatures that predict CIPN response to CBD.
Methods: Stool samples were collected from 18 cancer survivors pre- and post-CBD exposure. A minimal clinically important difference of 3.68 on the Functional Assessment of Cancer Therapy/Gynecologic-Oncology Group-Neurotoxicity questionnaire was used to classify patients into responders vs. non-responders. Ultra-high-performance LC-MS/MS untargeted metabolomics was performed using Q-Exactive Orbitrap and 16S rRNA gene (V4 region) sequencing was run using the Illumina MiSeq platform. Metabolomic and microbiome data were analyzed via MetaboAnalyst 6.0, and the DADA2 pipeline and Silva database on MicrobiomeAnalyst 2.0, respectively.
Results: Study participants (median age 63 years) were mostly female (83%), breast (56%) and colorectal (17%) cancer survivors. A higher relative abundance of metabolites (>500, p<0.05) was observed for the CBD responders vs. non-responders when represented on a hierarchical clustering heatmap. Five significantly different metabolic pathways were found via KEGG functional analysis: a) tyrosine metabolism, b) phenylalanine, tyrosine and tryptophan biosynthesis (PTT), c) lysine degradation, d) drug metabolism, e) ubiquinone and other terpenoid-quinone biosynthesis (p<0.05). PTT and lysine degradation were also significantly altered in cancer patients with CIPN compared to those without CIPN (Hua et al., 2025). Microbiome diversity profiles prior to CBD exposure also showed significant alpha diversity (Shannon index) differences associated with a clinical response to CBD.
Conclusion: Our preliminary results suggest that metabolomic and microbiome profiles may be helpful in personalizing CBD treatment for cancer survivors suffering from CIPN.