Marijuana is consistently the most widely used illicit drug among teenagers and most users first experiment it in adolescence. Adolescence is the period between childhood and adulthood, encompassing not only reproductive maturation, but also cognitive, emotional and social maturation and is characterized by a brain in transition that differs anatomically and neurochemically from that of the adult. The endocannabinoid system plays an important role in this critical phase for cerebral development, therefore a strong stimulation by the psychoactive component of marijuana, delta-9-tetrahydrocanabinol, that acts through the cannabinoid system, might lead to subtle but lasting neurobiological changes that can affect adult brain functions and behaviour. The literature here summarized, exploiting animal models of cannabis consumption, points to the presence of subtle changes in the adult brain circuits after heavy cannabis consumption in adolescence. These alterations lead to impaired emotional and cognitive performance, enhanced vulnerability for the use of more harmful drugs of abuse, and may represent a risk factor for developing schizophrenia in adulthood. The few studies examining the neurobiological basis of the altered behaviours demonstrate the presence of stable alteration in the endocannabinoid system that can trigger subsequent alteration in synaptic protein and synaptic morphology, thus altering the responsiveness of selected brain areas to different internal and external stimuli. These pre-clinical observations are strengthened by literature in humans where longitudinal studies often support the experimental results. There is an urgent need of multidisciplinary approaches combining behaviour with neurochemical and genetic studies to build a scientific based opinion on the long-lasting consequences of cannabis use in adolescence.