Psilocybin’s effect on depression by binding to serotonergic receptors in the basolateral amygdala

Abstract

This review investigates the interaction between psilocybin and the serotonin 2A receptor (5HT2AR) in the basolateral amygdala. With psilocybin being one of the psychedelics currently being studied for their positive therapeutic outcomes in the treatment of disorders like depression, anxiety and substance abuse disorder, it is of importance that the mechanisms surrounding these positive observations are elucidated, because when it becomes clear what is causing positive change, inspiration for future treatment options can arise as our understanding of how they work grows. One of the proposed mechanisms that aids in the alleviation of psychiatric symptoms is the increase of plasticity in the brain, and for this review, psilocybin’s role in inducing that in the basolateral amygdala is explored. For this, this review looks at how the amygdala functions under depression, especially what role it plays in anhedonia as a hallmark symptom of depression, and how this is alleviated through plasticity when psilocybin interacts with the 5HT2A receptor. This will then be viewed through the lens of canalisation, a concept closely related to Hebbian plasticity, describing psychopathology as an entrenched phenotype that is resistant to change, and explains conceptually why plasticity would be the opposite of this and give a different perspective as to why plasticity aids depression, or anhedonia, when depression is viewed as a canalised phenotype.