Cannabinoid CB1 receptor-sensitive neurodevelopmental processes and trajectories

As high-potency cannabis (with high Δ⁹-Tetrahydrocannabinol content) becomes easily accessible and widespread, it is of extreme importance for public health that a scientific platform is used to implement practical guidelines, particularly for at-risk populations. Many reviews have been written in the past decade summarizing the impact of cannabis in the developing brain. One critical concept frequently mentioned but not discussed in detail is whether there are sensitive neurodevelopmental events driving the age-specific sensitivity to cannabis, particularly those mediated by cannabinoid type 1 receptor signaling. By integrating available data from humans and animal models, the goal of the present expert review article is to provide a mechanistic overview on how cannabis exposure during sensitive periods of neural circuit plasticity and development can result in lasting consequences. Here we used the frontal cortex as a proxy to align the trajectory of the brain cannabinoid system between humans and rodents. Both the strengths and limitations of available mechanistic studies on the effects of cannabis and cannabinoids were discussed using a developmental framework from which neural circuit adaptations during sensitive periods are considered. Such an approach is needed to align key neurodevelopmental variables through the lifespan, which in turn will provide valuable insights applicable to the human brain by defining the underpinning mechanisms of sensitive periods and how the impact of cannabis changes from childhood to adolescence, and thereafter through young adulthood.