Short-term effects of cannabidiol after global hypoxia-ischemia in newborn piglets

Pediatr Res. 2016 Nov;80(5):710-718. doi: 10.1038/pr.2016.149. Epub 2016 Jul 21.


Background: Cannabidiol (CBD), a nonpsychoactive cannabinoid, has shown neuroprotective actions after neonatal hypoxia-ischemia (HI) in animals. We wanted to further explore the effects of CBD, alone and in conjunction with hypothermia, in a piglet model of global HI.

Methods: Fifty-five anesthetized newborn piglets were randomized to either controls (n = 7) or HI (n = 48) by ventilation with 8% O2 until mean arterial blood pressure reached 20 mmHg and/or base excess reached -20 mmol/l. After resuscitation piglets were randomized to either: vehicle (VEH), CBD 1mg/kg, VEH+hypothermia (H) or CBD 1mg/kg+H (each n = 12). Piglets were euthanized 9.5 h after HI and plasma, urine, cerebrospinal fluid, and brain tissue were sampled for analysis.

Results: HI induced global damage with significantly increased neuropathology score, S100B in cerebrospinal fluid, hippocampal proton magnetic resonance spectroscopy biomarkers, plasma troponin-T, and urinary neutrophil gelatinase-associated lipocalin. CBD alone did not have any significant effects on these parameters while CBD+H reduced urinary neutrophil gelatinase-associated lipocalin compared with VEH+H (P < 0.05). Both hypothermic groups had significantly lower glutamate/N-acetylaspartate ratios (P < 0.01) and plasma troponin-T (P<0.05) levels compared with normothermic groups.

Conclusion: In contrast to previous studies, we do not find significant protective effects of CBD after HI in piglets. Evaluation of CBD in higher doses might be warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Blood Pressure
  • Body Weight
  • Cannabidiol / pharmacology*
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hypothermia, Induced
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / pathology
  • Inflammation
  • Kidney / pathology
  • Magnetic Resonance Spectroscopy
  • Myocardium / pathology
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress
  • Oxygen
  • Swine


  • Biomarkers
  • Neuroprotective Agents
  • Cannabidiol
  • Oxygen