Cannabidiol/cannabigerol exposure and neuropathy-related outcomes after neurotoxic chemotherapy: a real-world cohort study.

BACKGROUND

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of neurotoxic chemotherapy, yet effective pharmacologic options for both prevention and treatment of established painful CIPN remain limited. Non-delta-9-tetrahydrocannabinol (THC) cannabinoids and related minor cannabinoids show antinociceptive effects in preclinical CIPN models, but their real-world clinical relevance remains unclear.

METHODS

We performed a retrospective secondary analysis of de-identified electronic health record (EHR) data using the TriNetX Research Network to examine whether documented cannabidiol/cannabigerol (CBD/CBG) exposure was associated with subsequent neuropathy-related diagnoses among adults receiving neurotoxic chemotherapy. Patients with neuropathy-related diagnoses on or before chemotherapy were excluded. Two Cox proportional hazards analyses were performed. The post-chemotherapy exposure analysis compared post-chemotherapy CBD/CBG exposure with post-chemotherapy exposure to gabapentin, pregabalin, or duloxetine. The pre-chemotherapy exposure analysis compared patients with documented CBD/CBG exposure within one year before chemotherapy to patients who had no documented CBD/CBG exposure during that pre-chemotherapy window. The outcome was a composite neuropathy-related diagnosis 30-365 days after the index event.

RESULTS

In the adjusted post-chemotherapy exposure model, 83 CBD/CBG-exposed patients were compared with 118,001 active-comparator patients. Post-chemotherapy CBD/CBG exposure was associated with lower hazard of subsequent neuropathy-related diagnosis-code outcomes (Hazard ratio [HR] = 0.162, 95% confidence interval [CI] = 0.041-0.649, p = 0.010). In the adjusted pre-chemotherapy exposure model, 162 CBD/CBG-exposed patients were compared with 633,329 controls. Pre-chemotherapy CBD/CBG exposure was not significantly associated with neuropathy-related diagnosis-code outcomes (HR = 0.859, 95% CI = 0.476-1.551, p = 0.614).

CONCLUSIONS

Post-chemotherapy CBD/CBG exposure was associated with lower observed hazard of neuropathy-related diagnosis-code outcomes, whereas pre-chemotherapy exposure was not significant. These exploratory findings require cautious interpretation because of sparse exposed-arm events, EHR exposure limitations, and potential competing-risk bias.