The changes in molecules such as IκB-α (Qin et al., 2018), NF-κB (Jiang et al., 2017; Qin et al., 2018), JNK (Jiang et al., 2018), Nrf2 (Bi et al., 2021), Akt (Bao et al., 2022), AMPK (Qiu et al., 2016a), CREB (Li et al., 2018), and BDNF (Li et al., 2018) may mediate the effects of sinomenine in CNS disorders, including cerebral ischemia, intracerebral hemorrhage, TBI, AD, PD, epilepsy, sleep disturbance, depression, multiple sclerosis, and morphine tolerance. Here, CREB1 is linked to major depressive disorder.