Hyperforin has been shown to improve synaptic plasticity via different pathways, including CaM-kinase IV (CaMKIV), PI3K/Akt, and Ras/MEK/ERK, enhancing the phosphorylation of cyclic adenosine monophosphate response element binding protein, associated with depression in primary hippocampal neurons and PC12 cells (Heiser et al., 2013). Here, CAMK4 is linked to major depressive disorder.