CREB1 and morphine dependence: Considering that morphine addiction is an aberrant deviant form of learning and memory (Chen et al., 2022b) and that pathological changes in NMDAR, CaMKII, or CREB are known to correlate with learning and memory (Ko et al., 2018), these results suggest that sinomenine may attenuate morphine dependence by reducing NMDAR-mediated Ca2+ influx and thus cAMP-CaMKII-CREB signaling (Figure 8).