TRPV1 and major depressive disorder: First, depressive and acute manic symptoms appeared to be positively affected by PEA add-on to conventional therapy in MDD (Ghazizadeh-Hashemi et al., 2018) and BPAD (Abedini et al., 2022) patients respectively, possibly thanks to PEA multi-faceted mechanism of action, including PPAR-α-mediated anti-inflammatory effects, GPR55 agonism (with implications for the modulation of monoaminergic neurons), TRPV1 allosteric modulation, glutamate neuro-toxicity prevention, and neurogenesis promotion (Petrosino and Schiano Moriello, 2020; Petrosino and Di Marzo, 2017).