some engineered cannabis plants and preparations can induce paranoia and psychosis even after single doses or short-term cannabis use and may even induce these in the long-term, structural brain modifications in younger brains [133,134]. Furthermore, chronic cannabis use has been associated with a higher risk of developing cannabis use disorder (CUD) and may lead to other substance use disorders (SUDs) [130,135,136,137], including heightened functional impairment of normal daily activities comparable to the harms observed with any SUD, as reviewed in [135,138,139]. A large proportion of long-term users would transition to CUD and most experience strong withdrawal symptoms after cessation [128,140,141,142,143], including irritability, anger or aggression, nervousness or anxiety, sleep disruption, decreased appetite, restlessness, or depressed mood, all of which could promote further drug seeking and relapse. Clinically, 50–95% of heavy users may suffer from some symptoms of cannabis withdrawal [140,141,142], with a meta-analysis reporting an overall prevalence of 47% [143]. Moreover, it has also been shown that long-term use of cannabis may lead to the use of other illicit drugs, which is reinforced by increased frequency and earlier onset of use [144], thus increasing the risk of SUDs and closely aligned mental illnesses, notably depression and anxiety. In a paradoxical
