Ego Dissolution and Psychedelic-Assisted Psychotherapy

Psychedelics are a class of psychoactive substances that induce profoundly altered states of consciousness, including transient, dose-dependent distortions in the subjective experience of oneself. 1 ] Called ego dissolution [ 2 This phenomenon is characterized by a reduction in self-referential awareness that defines normal waking consciousness, ultimately breaking the boundaries of one's own world and increasing feelings of unity with others and with the environment. 3 ] It is important to highlight that there is a renewed interest in the use of these substances in the treatment of various psychiatric conditions characterized by distortions of self-experience. 4 , 5 ]. Recent clinical studies have suggested that these substances may increase well-being [ 4 , 6 , 7 , 8 , 9 , 10 , 11 and provide therapeutic relief for those suffering from anxiety, depression, and addiction 4 , 9 , 12 , 13 , 14 , 15 ]

Converging evidence suggests that classic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, and dimethyltryptamine (DMT), stimulate serotonin (5-HT) receptors. _2A ) located in cortical pyramidal neurons, which is the main suggested mechanism of action for its hallucinogenic effect [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ] However, accumulated evidence from preclinical studies also emphasizes the role of the glutamate system in effects mediated by the 5-HT receptor _{2A in brain function [} 19 , 23 , 24 ] and in behavior [ 17 ]. Specifically, it has been suggested that the activation of 5-HT receptors _2A leads to a glutamate-dependent increase in the activity of pyramidal neurons in the prefrontal cortex [ 18 , 19 , 25 , 26 ], subsequently modulating the activity of the prefrontal network [ 16 ] Furthermore, increased extracellular glutamate has been suggested to activate AMPA receptors located on the same neurons, increasing the expression of brain-derived neurotrophic factor (BDNF)[ 16 , 27 , 28 ], a protein involved in neuronal survival and growth, and decreased in pathological populations [ 29 ]. Taken together, it has been suggested that glutamate release mediated by the 5-HT receptor _2A It is the common final pathway for the acute actions of psychedelics and a potential underlying mechanism of therapeutic effects. 16 ]

Reference: https://www.nature.com/articles/s41386-020-0718-8