Cannabinoid signalling in the immature brain: Encephalopathies and neurodevelopmental disorders, Onintza Sagredo et al., 2018

Cannabinoid signalling in the immature brain: Encephalopathies and neurodevelopmental disorders

Onintza Sagredo, Javier Palazuelos, Ana Gutierrez-Rodriguez, Valentina Satta, Ismael Galve-Roperh,  Jose Martinez-Orgado

Biochemical Pharmacology, 2018, 157, 85-96

DOI : 10.1016/j.bcp.2018.08.014


The endocannabinoid system exerts a crucial neuromodulatory role in many brain areas that is essential for proper regulation of neuronal activity. The role of cannabinoid signalling controlling neuronal activity in the adult brain is also evident when considering its contribution to adult brain insults or neurodegenerative diseases. In the context of brain genetic or acquired encephalopathies administration of cannabinoid-based molecules has demonstrated to exert symptomatic relief and hence, they are proposed as new potential therapeutic compounds. This review article summarizes the main evidences indicating the beneficial action of cannabinoid-derived molecules in preclinical models of neonatal hypoxia/ischemic damage. In a second part, we discuss the available evidences of therapeutic actions of cannabidiol in children with refractory epilepsy syndromes. Finally, we discuss the current view of cannabinoid signalling mechanisms active in the immature brain that affect in neural cell fate and can contribute to long-term neural cell plasticity.

Graphical abstract




CBD : cannabidiol
DS : Dravet syndrome
EC : endocannabinoid
ECS : endocannabinoid system
HI : hypoxia–ischemia
LGS : Lennox-Gastaut Syndrome
MRI : magnetic resonance imaging
NHIE : neonatal hypoxic ischemic encephalopathies
NP : neural precursor
OGD : oxygen and glucose deprivation


Endocannabinoid system, Hypoxia/ischemia, Refractory epilepsy, Cannabidiol, Neurogenesis, Neurodevelopment