Cannabis is the world's most widely used illicit substance, with an estimated number of 119–224 million users worldwide. In recent years we assisted to an increased effort aimed to individuate the brain circuits underlying cannabis addiction and dependence. Similarly to other drugs of abuse, repeated exposure to cannabinoids causes brain neuroadaptations that persist long after drug effects, contribute to the negative affective states during withdrawal, and ultimately facilitate relapse. Recently, considerable progress has been made in understanding the cellular and molecular consequences of prolonged cannabis use, among which is the identification of specific set of transcriptional regulations that develop differently after chronic cannabinoids and in the abstinent brain.