Cannabis, Endocannabinoids and Brain Development: From Embryogenesis to Adolescence.

The endocannabinoid signalling system (ECS) plays a critical role from the very beginning of embryogenesis. Accordingly, the ECS is engaged early on in nervous system development, starting from neurulation, supported by the identification of ECS components-both receptors and enzymes controlling endocannabinoid metabolism-at these early stages. In particular, regarding the brain, the ECS is involved in the tightly regulated sequence of events that comprise brain development, from neurogenesis to neuronal migration, morphological guidance for neuronal connectivity, and synaptic circuitry refinement. The importance of this broad role of the ECS across various brain development processes is further underscored by the growing understanding of the consequences of cannabis exposure at different developmental stages. Despite the considerable knowledge we have on the role of the ECS in brain development, significant gaps in our understanding remain, particularly regarding the long-term impact and underlying mechanisms of cannabis exposure at different developmental stages. This review provides an overview of the current state of knowledge on the role of the ECS throughout brain development, from embryogenesis to adulthood, and discusses the impact of cannabis exposure, especially during adolescence-a critical period of circuitry maturation and refinement coinciding with an increased risk of cannabis use.