CNR1 and cannabis dependence: Some relevant conclusions can be drawn from the available evidence: (1) specific CNR1 polymorphisms have been associated with significant cannabis withdrawal syndrome and craving; (2) the consequences of FAAH C385A rs324420 polymorphism on cannabis effects and the development of cannabis dependence vary according to the carrying allele (C or A); and (3) cannabis chronic exposure induces a down-regulation of CB1R (gene expression and binding) that is normalized or even increased during withdrawal.