Psilocin is a molecule found in psilocybin mushrooms, which are typically consumed recreationally for their hallucinogenic effects. Recently, studies have shown that psilocin can have almost immediate antidepressant effects in patients who are treatment-resistant to medications that increase serotonin levels in the synapse. Researchers believe that the molecule works by suppressing activity in the medial prefrontal cortex and amygdala, which are both brain structures involved in the emotional aspect of depression. However, psilocin’s exact mechanism of action and binding characteristics in the body remain unknown. Using Chimera for visualization and AutoDock Tools and AutoDock Vina for docking, psilocin and serotonin were separately docked in a crystallized 5-HT2A receptor. Key residues were identified using existing information in the RCSB database. Once the ligands were docked, the lengths of the potential bonds between atoms of the ligands and the key residues within the receptor were measured to determine if they were close enough to each other to interact. Serotonin had multiple possible hydrogen bonds and hydrophobic interactions; however, psilocin only had one potential hydrophobic interaction. The main structural difference between psilocin and serotonin is the presence of the phosphate group in psilocin; therefore, studies of phosphate’s binding properties within the 5-HT2A receptor could potentially provide insight on the efficacy of psilocin.

This report is a learning artifact from the Spring 2020 semester of the UH-4504 Honors Topics in Discovery and Innovation Studios course titled Drug Discovery and Design in the Digital Age. This report should not be used or interpreted as a peer reviewed paper.