Psychedelic Receptor Dynamics: Unveiling the Molecular Insights of Synthetic LSD for Accelerated Drug Discovery (2024)

Undergraduates: Elena Vargas, Fengjun Tian, Chethana Chennuri

Faculty Advisor: Rachel Penton
Department: Neuroscience

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Serotonin (5-HT) receptors G protein-coupled receptors that exist in various subtypes. These receptors display a wide variety of functions that affect brain pathways, specifically those associated with mood disorders (Cao et. al, 2022). As the research field expands, scientists are investigating the interactions of synthetic lysergic acid (LSD) at the 5-HT2A receptor as a way to mediate the symptoms of schizophrenia (Cao et al., 2022). Due to its similarity to 5-HT2A, we decided to focus on the potential of the 5-HT2B receptor to mediate effects of synthetic LSD via the β-arrestin-1 pathway (Wacker et al., 2018). We conducted design-related research about the novel mechanism of action of the binding of β-arrestin-1 to 5-HT2B in the presence of synthetic LSD and how that enhances the effects of the drug. We then aimed to explain the functionality by presenting a physically manipulatable, 3D printed model showcasing receptor structure and ligand representation. After many prototypes, the 3D printed model demonstrates the activation of the β-arrestin-1 pathway and increase in difficulty coupling with Gq as LSD changes the conformation of the receptor.