CNR1 and major depressive disorder: In contrast, phytocannabinoids such as cannabidiol and tetrahydrocannabivarin, produced by cannabis, exhibit antagonistic activity on CB1R signaling and do not show any adverse side effects such as psychoactive effects, depression, or anxiety in early studies [10,11], thereby serving as potential candidates for the treatment of diabetes and its complications, including those responsive to SGLT2 inhibition.