Long-term consequences of adolescent cannabinoid exposure in adult psychopathology

Abstract

Marijuana is the most widely used illicit drug among adolescents and young adults. Unique cognitive, emotional, and social changes occur during this critical period of development from childhood into adulthood. The adolescent brain is in a state of transition and differs from the adult brain with respect to both anatomy (e.g., neuronal connections and morphology) and neurochemistry (e.g., dopamine, GABA, and glutamate). These changes are thought to support the emergence of adult cerebral processes and behaviors. The endocannabinoid system plays an important role in development by acting on synaptic plasticity, neuronal cell proliferation, migration, and differentiation. Delta-9-tetrahydrocanabinol (THC), the principal psychoactive component in marijuana, acts as a partial agonist of the cannabinoid type 1 receptor (CB1R). Thus, over-activation of the endocannabinoid system by chronic exposure to CB1R agonists (e.g., THC, CP-55,940, and WIN55,212-2) during adolescence can dramatically alter brain maturation and cause long-lasting neurobiological changes that ultimately affect the function and behavior of the adult brain. Indeed, emerging evidence from both human and animal studies demonstrates that early-onset marijuana use has long-lasting consequences on cognition; moreover, in humans, this use is associated with a two-fold increase in the risk of developing a psychotic disorder. Here, we review the relationship between cannabinoid exposure during adolescence and the increased risk of neuropsychiatric disorders, focusing on both clinical and animal studies.

Keywords: adolescence; behavior; cannabinoids; long-term consequences; psychosis.

Figure 1

Schematic overview of the various stages of adolescence in rats. To model the effects of cannabinoid exposure at different developmental stages, rats can be treated chronically throughout the entire adolescent period (from PND28 through PND61) or during specific stages of adolescence, including early adolescence (beginning at PND28), mid-adolescence (beginning at PND38), or late adolescence (beginning at PND49). The long-term effects of adolescent cannabinoid exposure can then be measured in adulthood. PND, postnatal day.