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Investigating the effectiveness of cannabidiol to mitigate the adverse consequences of exposure to neonatal procedural pain

Timmerman, B.; Honeycutt, J. A.; Skully, J.; Patel, D.; Kahn, W.; Neagu, A.; Baez, E.; Battagliese, Q.; Brummelte, S.

2025-02-25 neuroscience
10.1101/2025.02.21.639541 bioRxiv
Show abstract

Repeated painful procedures are associated with a multitude of effects on neurodevelopment in preterm infants, and current methods of neonatal pain management are unable to prevent the distress and long-term changes induced by these procedures. Cannabidiol (CBD) may be particularly effective for neonatal pain management because it reduces pain unpleasantness ratings, mitigates biological stress responses, and has minimal side effects in adults. However, there is limited research on the effects of neonatal CBD exposure. The present study investigated the efficacy of CBD treatment in mitigating behavioral responses to neonatal pain exposure. This was measured acutely through changes in ultrasonic vocalization (USV) emissions, as well as across development on long-term behavioral outcomes. We show that neonatal pain exposure decreased USV emission and increased adult anxiety-like behavior in male rats. Neonatal CBD treatment also decreased USVs in male pups but was unable to rescue the increased anxiety-like behavior in adulthood. Additionally, neonatal CBD increased baseline corticosterone levels in adult male subjects and decreased adult female body weight. More research is needed to determine whether CBD may be a safe and effective neonatal pain management medication. HighlightsO_LICBD reduced USV emissions on PD 2 and 3 in males, but not on later days C_LIO_LIPain exposure increased adult anxiety-like behavior in males C_LIO_LINeonatal CBD exposure resulted in decreased adult female body weight. C_LIO_LICBD had no permanent effects on measurements of neurodevelopment or adult behavior C_LIO_LICBD does not seem to mitigate effects of neonatal pain exposure C_LI

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