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Medulloblastoma is the most common malignant paediatric brain tumour. Standard treatment includes a combination of surgery, craniospinal radiotherapy and adjuvant chemotherapy. The chemotherapy agent Vincristine causes potent inhibition of tumour growth, however, high levels of toxicity and intrinsic drug resistance mechanisms, limit its clinical use. Jerantinine is a novel aspidosperma indole alkaloid that, like Vincristine, works by destabilising microtubule growth and hence blocks cell division. Here, we tested the hypothesis that Jerantinine would be an effective alternative to Vincristine in medulloblastoma. Jerantinine, like Vincristine, caused a dose-dependent decrease in cell viability and colony formation in medulloblastoma cell lines. Cytotoxicity of Vincristine could be potentiated with the ABCB1 inhibitor Verapamil, however there was no potentiation of Jerantinine’s activity indicating that Jerantinine functions independently of intrinsic ABCB1 expression and is able to circumvent this drug resistance mechanism. The effect of Jerantinine treatment was also assessed in 3D spheroid culture. Spheroid viability decreased with increasing concentrations of Jerantinine, as measured using the CellTiter-Glo(®) 3D cell viability assay. Automated imaging analysis (Celigo(®) cytometer) also showed an increase in cell death at a range of Jerantinine concentrations over 48 hours. Confocal microscopy showed comparable effects of Jerantinine and Vincristine in medulloblastoma cell lines, including cytoskeletal defects, inhibition of tubulin polymerisation and defective cell division. However unlike Vincristine, Jerantinine caused no visible disruption to cellular morphology of neural stem cells. These results suggest that Jerantinine is an effective, tumour-specific alternative to Vincristine in the treatment of paediatric medulloblastoma.