Interactions and activity of lysergol derivatives at 5 HT1A and 5-HT2A–C receptors

Abstract

Traditional use of psychedelics has historically remained restricted between religious ceremonies and countercultural movements. With the pathophysiology of various neuropsychiatric disorders becoming clearer, the world has encountered a raising interest in psychedelic research. Previous studies have shown that 5-HT1A and 5-HT2C receptors play a significant role in neuropsychiatric disorders, whereas 5-HT2A and 5-HT2B are known for their hallucinatory and cardiovascular effects. The main objective of this study is to investigate the binding interactions of lysergol derivatives in serotonin and TrkB receptors through computational methods.

Our findings reveal that the (+)-isomers of lysergol derivatives generally exhibit stronger binding compared to their (−)-isomer counterparts in 5-HT1A and 5-HT2C receptors, without the functional activity in 5-HT2A and 5-HT2B receptors. Instead, both (+)- and (−)-isomers show a comparable binding in TrkB receptors. The results reveal options for further research that could lead to the discovery of novel treatment options for various neuropsychiatric diseases. Our findings suggest that (+)-isomers of lysergol derivatives could be used for treating these disorders, while (−)-isomers could be explored to enhance neuroplasticity and combat depression with a minimal risk of adverse effects.