TAAR1mainly couples to heterotrimeric G protein, Gs, to stimulatecyclic adenosine monophosphate (cAMP) production.22,23 TAAR1 activation by trace amines modulates neurotransmission inDA, glutamine, and serotonin neurons in the CNS.24−30 Notably, PEA shares a phenylethylamine moiety with the psychotropicdrugs (Figure 1e) AMPHand its derivative METH, leading to the hypothesis that PEA is anendogenous AMPH.31,32 Low PEA levels have been associatedwith depression,33 whereas elevated PEAlevels have been linked to schizophrenia, mania symptoms, and theantidepressant effects of exercise.32,34,35. The gene discussed is TAAR1; the disease is major depressive disorder.