Cannabis and the Mesolimbic System

Cannabis sativa (hemp) is a flowering annual plant whose phytochemical by-products, hashish and marihuana, are the most widely produced and most frequently used illicit drugs in Europe. ?9-Tetrahydrocannabinol is the primary psychoactive constituent, responsible, in a dose-related manner, for euphoria, cognitive effects, and psychotic symptoms, as well as the addictive potential of smoked cannabis due to its interference with the mesolimbic dopaminergic system. Cannabis as well as endocannabinoids acts mainly at the presynaptic levels in several brain regions, including the nucleus accumbens and ventral tegmental area, where it modulates synaptic activity. Through the modulation of ?-aminobutyric acid and glutamate release by the cannabinoid type 1 receptor, cannabinoids can activate the dopaminergic mesolimbic system and induce dependence in regular or heavy marijuana users. Overall, cannabis may provoke a profound alteration in brain neurotransmission and, in particular, in the mesolimbic system, where it can rearrange the molecular architecture at the synaptic level. In this way cannabis consumption can result in the disruption of the endocannabinoids' protective role of ongoing synaptic brain function, especially in the mesocorticolimbic circuitry.