Endocannabinoid system contributions to sex-specific adolescent neurodevelopment

With an increasing number of countries and states adopting legislation permitting the use of cannabis for medical purposes, there is a growing interest among health and research professionals into the system through which cannabinoids principally act, the endocannabinoid system (ECS). Much of the seminal research into the ECS dates back only 30 years and, although there has been tremendous development within the field during this time, many questions remain. More recently, investigations have emerged examining the contributions of the ECS to normative development and the effect of altering this system during important critical periods. One such period is adolescence, a unique period during which brain and behaviours are maturing and reorganizing in preparation for adulthood, including shifts in endocannabinoid biology. The purpose of this review is to discuss findings to date regarding the maturation of the ECS during adolescence and the consequences of manipulations of the ECS during this period to normative neurodevelopmental processes, as well as highlight sex differences in ECS function, important technical considerations, and future directions. Because most of what we know is derived from preclinical studies on rodents, we provide relevant background of this model and some commentary on the translational relevance of the research in this area.