An Overview of Cannabinoid Interactions With Common Pediatric Antineoplastic Agents

As interest in the use of cannabinoids for supportive care in pediatric cancers grows, there are emerging concerns about potential interactions with antineoplastic agents. This review provides an overview of potential drug-drug interactions between cannabinoids and 25 antineoplastic agents commonly used in pediatric hematology/oncology. Antineoplastic agents were stratified into low, medium, or high interaction risk based on the potential impact of cannabinoids on metabolic and/or pharmacodynamic pathways. The antineoplastic agents identified as high risk for interactions with cannabinoids included cyclophosphamide, doxorubicin, etoposide, ifosfamide, irinotecan, vinblastine, and vincristine. Key mechanisms of interaction include inhibition of cytochrome P450 enzymes and UDP-glucuronosyltransferases and modulation of drug transporters such as P-glycoprotein and breast cancer resistance protein. There is emerging evidence of a synergistic effect between cannabinoids and antineoplastic agents such as temozolomide, vinblastine, vinorelbine, and irinotecan. Pediatric patients exhibit developmental differences in drug metabolism and transporter expression, yet most pharmacokinetic data on cannabinoids are extrapolated from adult studies. There is a lack of pediatric-specific safety, efficacy, and dosing data that underscores the need for age-appropriate studies to ensure safe and effective integration of cannabinoids in pediatric cancer care.