Pilot study of cannabidiol (CBD) to prevent neuropathy (CIPN) in colorectal cancer (CRC) chemotherapy (Ctx).

Abstract

TPS253 Background: Oxaliplatin (Ox) remains a cornerstone of CRC therapy, but its utility is limited by CIPN—a debilitating, dose-limiting toxicity that compromises quality of life and treatment adherence. Despite its prevalence, no effective preventive strategies exist. The endocannabinoid system, central to pain modulation, inflammation, and neuronal excitability, offers a novel therapeutic target. CBD, a non-psychoactive phytocannabinoid, exerts anti-inflammatory, neuroprotective, and analgesic effects in preclinical neuropathy models and has shown early promise in retrospective studies. However, no prospective trials have rigorously tested CBD for Ox-induced CIPN in CRC, making this study a first-of-its-kind effort to address a critical unmet need. Methods: GI-249/IRB 25-1032 is a National Institutes of Health–funded (1R21CA292276-01A1), single-institution, randomized pilot study evaluating feasibility and acceptability of hemp-based CBD supplementation during Ox-based Ctx. Thirty patients with advanced CRC, initiating Ox-based Ctx with preserved liver function and no major psychiatric illness, will be randomized 2:1 to receive oral CBD (150 mg twice daily) starting one day before each Ox cycle and continuing for seven days post-infusion versus Ctx alone. The primary endpoint is feasibility (binary outcome: ≥70% of patients missing ≤3 doses per cycle in ≥75% of Ox treatments) and acceptability (assessed via the FIM Acceptability Survey). With 10 participants in the control arm, the study has 80% power to test a discouraging response rate of 40% versus an encouraging rate of 76% (1-sided α=0.055, binomial exact test). Secondary endpoints include comparing rates of acute and chronic CIPN and other adverse events between the two groups (CTCAE v5, FACT GOG NTX-13, Brief Pain Inventory). Correlative analyses will evaluate miRNAs and pro-inflammatory cytokines associated with neuropathy and compare between the groups, aiming to elucidate CBD’s neuroprotective mechanisms and identify predictive biomarkers. This pilot study will inform the design of future trials and advance the understanding of CBD as a novel approach in reducing CIPN in CRC patients. Clinical trial information: pending .