The regular use of cannabis during adolescence is of particular concern because use by this age group seems to be associated with an increased likelihood of deleterious consequences, as reported by several epidemiologic studies. However, despite their unquestionable value, epidemiologic data are inconclusive. Modeling the adolescent phase in animals appears to be a useful approach to investigate the impact of cannabis use on the adolescent brain. In these models, adolescent cannabinoid exposure has been reported to cause long-term impairment in specific components of learning and memory and to have differential effects on anxiety, social behavior, and depressive-like signs. These findings suggest that it may represent, per se or in association with other hits, a risk factor for developing psychotic-like symptoms in adulthood. The neurobiological bases of this association include the induction of alterations in the maturational events of the endocannabinoid system occurring in the adolescent brain. Alterations in the endocannabinoid system may profoundly dysregulate developmental processes in some neurotransmitter systems, such as gamma-aminobutyric acid and glutamate, mainly in the cortex. The resulting picture strongly resembles the one present in schizophrenic patients, highlighting the translational value of this experimental approach.