Cannabis effects on the adolescent brain

Chronic cannabis exposure during adolescence can result in persistent deficits in cognitive domains such as attention, memory, and processing speed. Cannabis use during adolescence is also linked to an increased risk for psychiatric disorders, including psychosis (schizophrenia), depression, anxiety, and substance use disorders, later in life. Notably, not all cannabis users exhibit these long-lasting behavioral and cognitive impairments, suggesting there is a genetic vulnerability, i.e., a gene-environment relationship for cannabis sensitivity. Unfortunately, little is known about the mechanisms of individual susceptibilities to the adverse effects of cannabis use in adolescence. The molecular mechanisms of gene and environment interactions differ across cell types, and recent studies have only begun to identify the molecular cascades activated by delta-9-tetrahydrocannabinol (Δ9-THC) in a cell-type-specific manner. In this chapter, we review these interactions and their contributions to cannabis sensitivity and to the development of long-lasting behavioral abnormalities. We also lay out the known cell-type-specific mechanisms of the susceptibilities to the adverse effects of cannabis and discuss the proinflammatory signaling pathways involved in Δ9-THC-induced behavioral impairments. Finally, we highlight new avenues to study the vulnerability to adverse effects of Δ9-THC exposure, specifically, changes in brain cell energetics and the insights gleaned from studies in humans and animal models.