Pre ICPR Events

About

Pre ICPR Events

About

Christopher Beaudoin, MSc

University of Cambridge

Speaker Bio

Chris’s dissertation research is directed towards developing new drugs to target infectious diseases (tuberculosis, leprosy, COVID-19) using biochemistry, bioinformatics, and evolutionary biology methodologies. Alongside the thesis work, he is interested in using techniques learned during the PhD to investigate the biochemical mechanisms underlying changes in consciousness. These projects comprise elucidating the mechanisms of action of psychedelics binding to their respective receptors (e.g. serotonin receptor 2a) and collaborating with neurologists and neurosurgeons to explore biochemical interactions at the brain-computer interface (e.g. deep brain stimulation). Chris will attend medical school in the UK this upcoming fall, following the completion of the PhD. Looking forward, Chris hopes to pursue the connections between biochemical, physiological, and clinical effects of psychedelics and is welcoming of any potential collaborative endeavours.

ICPR 2024 Abstract

Structural and molecular determinants of hallucinogenic 5HT2A receptor signaling

The 5-hydroxytryptamine receptor 2A (5HTR2A) binds to serotonin (5-hydroxytryptamine) and additional neurotransmitters to modulate changes in perception, mood, and neural activity. Additionally, studies have confirmed that 5HTR2A is one of the primary receptors for psychedelic compounds, such as lysergic acid diethylamide (LSD), and largely mediates the activation of signaling pathways that induce hallucinogenic states. LSD is categorized amongst structurally-similar ergot-derived compounds, ergolines, used to treat a wide variety of illnesses. Several non-hallucinogenic ergolines, such as lisuride, are almost identical in structure to LSD. The structural requirements for inducing hallucinogenic states are not completely understood. Although the downstream cellular signaling effects and molecular structures of 5HTR2A bound to LSD and lisuride have been determined, a comprehensive comparison of the structural changes in 5HTR2A induced by hallucinogenic and non-hallucinogenic ergolines has yet to be performed. Molecular dynamics (MD) simulations have been used to study protein-drug interactions and conformational changes over various timescales. Thus, MD simulations of hallucinogenic (LSD, 1D-LSD, ergine) and non-hallucinogenic (lisuride, methylergometrine, three non-psychoactive isomers of LSD) ergoline derivatives binding to 5HTR2A were conducted. In summary, τ-randomly accelerated MD simulations revealed that hallucinogenic compounds share similar intermolecular dissociation pathways and markedly high affinities and low dissociation rates. Novel conformational pathways were discovered using umbrella sampling MD, which revealed consistent structural changes in 5HTR2A with hallucinogenic compared to non-hallucinogenic compounds. These data may be used to better understand the mechanisms underlying psychedelic-induced hallucinations and predict the hallucinogenic potential of novel non-hallucinogenic psychedelics designed to treat depression, anxiety, and other mental conditions.

© 2007-2024 ICPR by OPEN Foundation, Amsterdam, the Netherlands
© 2007-2024 ICPR by OPEN Foundation, Amsterdam, the Netherlands
© 2007-2024 ICPR by OPEN Foundation, Amsterdam, the Netherlands