Medical cannabis, melatonin and oxygen-ozone therapy for neuroblastoma: two case reports

Abstract Background Neuroblastoma is the most common and lethal solid tumor in children, with high-risk cases showing only a 50% 5-year survival rate. Increasing attention has been directed toward integrative strategies exploiting compounds with potential anticancer and cytoprotective properties. Medical cannabis has been reported to modulate tumor cell proliferation, apoptosis, inflammation, and immune responses through the endocannabinoid system. Melatonin exhibits tumor-suppressive effects, including antioxidant activity, regulation of circadian biology, mitochondrial protection, and enhancement of apoptosis in tumor cells. Oxygen-ozone therapy has been proposed to improve tissue oxygenation, modulate oxidative stress, and influence tumor metabolism through controlled redox signaling. The rationale for combining these approaches lies in their potential complementary actions on oxidative stress regulation, mitochondrial function, immune modulation, and tumor metabolic vulnerability. Case presentation We report two pediatric patients with metastatic stage IV neuroblastoma refractory or poorly responsive to conventional treatments. Both patients subsequently received an integrative regimen based on medical cannabis, melatonin, and oxygen-ozone therapy. Following initiation of the combined treatment, both patients showed progressive clinical improvement, weight recovery, and complete regression of detectable disease on imaging. They remain in long-term disease-free status, with no significant adverse effects reported during the integrative treatment period. Conclusions These two cases evidenced as this integrative approach contributed to durable remission and good tolerability in high-risk pediatric neuroblastoma. However, the evidence remains extremely limited. Further preclinical and prospective clinical studies are required to elucidate mechanistic interactions, evaluate potential synergy, and define optimal therapeutic protocols for this integrative approach.