Nonetheless, it was later withdrawn from the market due to higher risks of mental side effects (such as depression, anxiety, and suicidal thoughts), as clinical trials showed [70, 71].Recent years have seen the development of various new peripheral restricted CB1 inhibitors [72–74] (such as SLV319, JD5037, and AM6545, inclusive in this study), selectively inhibiting CB1 receptor activity in peripheral tissues to minimize brain exposure, while preserving mammalian receptor affinity and selectivity, potentially offering benefits in managing complications [75]. This evidence concerns the gene CNR1 and major depressive disorder.