The disease hypoxic-ischemic encephalopathy (HIE) is a damage to the brain due to a lack of oxygen and blood flow. It occurs as a result of a lack of oxygen (asphyxia) and the resulting reduced blood flow to the nervous tissue during birth. In industrialized countries the incidence is estimated at 0.5 to 6 percent live births.
Risks for brain damage caused by oxygen deficiency
Several factors can increase the risk of newborns suffering brain damage from oxygen deprivation. These include complications before birth such as rupture of the uterus or umbilical cord and placental abruption.
There is another risk factor if the heartbeat of the unborn baby slows down as there is a risk of oxygen deficiency. If there is a significant increase in lactate (a metabolic product in the blood of the unborn child), it already indicates a lack of oxygen in the body cells.
Modulation of the endocannabinoid system
Perinatal brain injury might be caused by various damaging events such as asphyxia or stroke-induced focal ischemia during or shortly after birth. Characteristic manifestations of these diseases are the occurrence of oxidative stress, glutamate excitotoxicity and inflammation of nervous tissue (neuroinflammation). This combination may lead to long-lasting functional impairment, brain lesion formation and apoptotic necrotic cell death.
Treatment options for affected newborns are very limited. There is a high demand for new therapeutic options aimed at preventing brain damage. The endocannabinoid system could play an important role as it is involved in the control of many central and peripheral functions. Regarding to this the modulation of the endocannabinoid system has been shown to be effective in neuroprotection (protection of neurons by pharmacological methods) in various studies, mainly in animal models.
Spanish researchers from the Complutense University of Madrid state that the beneficial role of the endocannabinoid system has also been shown in studies to control neurogenesis (formation of neurons during the embryonic period) and recovery of brain white matter in neonatal brain injury (1).
In their review researchers summarize that modulation of the endocannabinoid system by administration of exogenous cannabinoids may have beneficial effects after perinatal brain injury. Thus, the modulation of the endocannabinoid system is a novel approach to preventing permanent brain injury in newborns.
CBD and hypothermia in HIE
Researchers at King’s College London found that moderate hypothermia (hypothermia of the body) resulted in improved neurocognitive outcomes after perinatal asphyxia (2).
Several studies have already provided evidence that cannabidiol (CBD) may have a beneficial effect on the brain (3). Spanish researchers from the Instituto de Investigación Sanitaria San Carlos (IdISSC) in Madrid investigated therefore the efficacy of the combination of hypothermia and CBD in newborn hypoxic-ischemic piglets (4).
In conclusion the researchers state that the hypoxic-ischemia-induced increases in various values were not reversed by either hypothermia or CBD alone, but were reversed by the combination of the two therapies.
Other interesting study
The Department of Neonatology in Madrid investigated the relevant therapeutic time window for the effect of CBD in a mouse model of neonatal brain injury (5).
Nine- to 10-day-old mice received 1 mg/kg CBD at various time intervals after being subjected to HI insult (10 percent oxygen for 90 minutes). Magnetic resonance imaging and histological examinations were used to assess brain damage after seven days. Mice that received CBD as late as 18 hours after the HI insult also showed neuroprotective effects.
The fact that the endocannabinoid system plays an important role in various processes (including the brain) and can be modulated by cannabinoids such as cannabidiol (CBD) has been proven by numerous studies. Much more research is needed to better understand CBD’s mechanisms of action against brain damage in neonates. The studies show positive results, from which no therapy recommendation can yet be derived.
(1) Fernández-López D, Lizasoain I, Moro MA, Martínez-Orgado J. Cannabinoids: well-suited candidates for the treatment of perinatal brain injury. Brain Sci. 2013;3(3):1043-1059. Published 2013 Jul 10. doi:10.3390/brainsci3031043
(2) Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, Goodwin J, Halliday HL, Juszczak E, Kapellou O, Levene M, Linsell L, Omar O, Thoresen M, Tusor N, Whitelaw A, Edwards AD; TOBY Study Group. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014 Jul 10;371(2):140-9. doi: 10.1056/NEJMoa1315788. PMID: 25006720.
(3) Campos AC, Fogaça MV, Sonego AB, Guimarães FS. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol Res. 2016 Oct;112:119-127. doi: 10.1016/j.phrs.2016.01.033. Epub 2016 Feb 1. PMID: 26845349.
(4) Barata L, Arruza L, Rodríguez MJ, Aleo E, Vierge E, Criado E, Sobrino E, Vargas C, Ceprián M, Gutiérrez-Rodríguez A, Hind W, Martínez-Orgado J. Neuroprotection by cannabidiol and hypothermia in a piglet model of newborn hypoxic-ischemic brain damage. Neuropharmacology. 2019 Mar 1;146:1-11. doi: 10.1016/j.neuropharm.2018.11.020. Epub 2018 Nov 20. PMID: 30468796.
(5) Mohammed N, Ceprian M, Jimenez L, Pazos MR, Martínez-Orgado J. Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice. CNS Neurol Disord Drug Targets. 2017;16(1):102-108. doi: 10.2174/1871527315666160927110305. PMID: 27686886.