Role for Endocannabinoids in the Developing Brain

The increased public awareness and legalization of marijuana use in the United States has inspired this line of research in elucidating the role of endocannabinoids in the developing brain, more specifically evaluating the potential impact of cannabis use during pregnancy. The role of endocannabinoids in mediating brain development is poorly understood, yet these neural modulators are ubiquitously distributed and expressed relatively early in fetal life. Sex differences in the brain are established early in life and endocannabinoids have been implicated as essential mediators of cell number in the developing amygdala in the laboratory rat animal model. 

  • Endocannabinoids are the endogenous ligands for the CB1 and CB2 receptors on which components of cannabis act to alter neural function. The developing hippocampus and amygdala are central brain regions for emotional and cognitive behaviors and are strongly impacted by endocannabinoids, which may include effects on non-neuronal cells such as microglia.

  • In the amygdala, microglia appear to be controlling both cell number and phenotype in a sex-specific manner, with the source of the sex difference being endocannabinoid tone. 

    • Microglial phagocytic activity is mediated by CB1 (and possibly CB2) receptor activation. The contents of microglial phagocytic cups suggests the engulfment of both mature and newly born live neurons. [Neuron, VanRyzin et al, 2019]

  • In the hippocampus, we have also observed a sex difference in cell genesis but in the opposite direction to that of the amygdala.