Animal studies have consistently demonstrated that delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis [20], is able to disrupt the regulatory role of the endogenous cannabinoid system [21], inducing neurotoxic changes in brain regions rich with cannabinoid receptors that might dramatically affect the process of maturational refinement of cortical neuronal networks [22]–[24] and lastly promote changes in brain structure and alter emotional and cognitive performance [25], particularly if the exposure has been during the adolescent period [26], [27]. In contrast to animal literature, results from human studies investigating chronic cannabis users are often inconsistent. These discrepancies may be due to heterogeneity in socio-demographic characteristics of the population studied, imaging techniques employed, as well as differences in drug usage patterns and psychiatric comorbidities that may not always be apparent or result in contact with mental health services and hence may not be appropriately controlled for in studies where participants are screened for presence of co-morbid psychiatric disorder merely by enquiring about previous contact with mental health services [28]–[30]. However, overall the results suggest that long-term cannabis use may result in persistent
