“Neonatal hyperoxia induces oxidative and inflammatory stress that disrupts cardiac maturation and contributes to long-term cardiovascular morbidity in individuals born preterm. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with antioxidant and anti-inflammatory properties, has demonstrated protective effects in neonatal hyperoxic injury in other organs; however, its impact on the developing heart remains unclear.
This study investigated whether CBD mitigates hyperoxia-induced cardiac injury in a neonatal mouse model. Newborn mice were exposed to 80% O2 for 48 h from postnatal day (P)5 to P7 and received vehicle, 10 mg/kg CBD, or 30 mg/kg CBD intraperitoneally, while controls remained in room air. Hearts were collected at P7 or after recovery until P14. Hyperoxia triggered oxidative stress (Nrf2), inflammation (IL1β, TNFα, IL6, CXCL1; p < 0.05), and dysregulated apoptosis/autophagy, leading to reduced cardiomyocyte proliferation (Ki67+ -50% at P14; p < 0.01) and adverse remodeling (hypertrophy, fibrosis; p < 0.01).
CBD attenuated these responses and normalized autophagy (Atg5, Atg12; p < 0.05). Notably, 10 mg/kg CBD, but not 30 mg/kg, preserved proliferative capacity and reduced wall thickness, suggesting a narrow therapeutic window, while both doses limited collagen deposition and apoptosis (Casp3, AIF; p < 0.05). Several effects were sex-dependent, with males exhibiting more pronounced long-term structural and proliferative impairments and greater responsiveness to low-dose CBD.
These findings identify CBD as a potential cardioprotective modulator of neonatal hyperoxia-induced injury and highlight the importance of dose- and sex-specific mechanisms in early cardiac maturation.”
https://pubmed.ncbi.nlm.nih.gov/41516025
“In summary, this study demonstrates that neonatal hyperoxia induces persistent oxidative, inflammatory, and structural cardiac damage and that CBD administration attenuates these effects in a dose-dependent manner, preserves cardiomyocyte proliferation, and reduces maladaptive remodeling at optimal dosages. These findings underscore the potential of CBD as a cardioprotective intervention in the neonatal period, provided that dosage, timing, and developmental safety are carefully considered. Translation into clinical practice will require rigorous functional, mechanistic, and safety studies. Nonetheless, the present data support further investigation of CBD in the context of neonatal oxygen therapy and cardiac protection.”