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

Graziane N.; Macherla A.; Giampetro M. · Frontiers in pain research (Lausanne, Switzerland) · 2026

**Background & Methods** This retrospective secondary analysis examined electronic health record data from the TriNetX Research Network to evaluate whether cannabidiol/cannabigerol (CBD/CBG) exposure was associated with neuropathy-related diagnoses in adults receiving neurotoxic chemotherapy. Two Cox proportional hazards models were performed: one comparing post-chemotherapy CBD/CBG exposure to standard neuropathic pain medications (gabapentin, pregabalin, duloxetine), and another comparing pre-chemotherapy CBD/CBG exposure to no exposure, with neuropathy-related diagnosis codes assessed 30-365 days after the index event. **Key Findings** - Post-chemotherapy CBD/CBG exposure (n=83) was associated with significantly lower hazard of subsequent neuropathy-related diagnosis-code outcomes compared to active comparators (n=118,001): HR=0.162 (95% CI=0.041-0.649, p=0.010). - Pre-chemotherapy CBD/CBG exposure (n=162) showed no significant association with neuropathy-related outcomes compared to controls (n=633,329): HR=0.859 (95% CI=0.476-1.551, p=0.614). - Timing of exposure appeared critical, with post-chemotherapy CBD/CBG use correlating with reduced neuropathy diagnosis coding, suggesting potential therapeutic benefit when administered after chemotherapy initiation. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This study has significant limitations warranting cautious interpretation. The authors acknowledge sparse exposed-arm events, particularly in the post-chemotherapy analysis (n=83), which reduces statistical power. EHR-based exposure documentation may underestimate actual cannabis use and lacks standardization regarding product composition, dosing, and duration. The study design cannot establish causation—associations may reflect confounding, selection bias, or competing-risk bias (patients with severe neuropathy might preferentially use conventional medications). Neuropathy assessment relied on diagnosis coding rather than validated clinical instruments, potentially introducing misclassification bias. The pre-chemotherapy null finding contrasts with post-chemotherapy benefit, but both analyses are exploratory. This is descriptive epidemiological evidence (Level III-IV) insufficient to support clinical recommendations. Rigorous prospective randomized controlled trials with standardized CBD/CBG dosing, validated neuropathy assessments, and safety monitoring are needed to determine efficacy for chemotherapy-induced peripheral neuropathy prevention or treatment.

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