Sponsor: David Olson, Ph.D. MED: Biochem & Molecular Med Psychedelics have garnered recent interest as treatments of neurological disorders due to their ability to induce neuronal growth and repair. However, their underlying biological mechanism is not understood, as psychedelic activity involves numerous receptors and signaling pathways, making it difficult to elucidate which pathways or proteins cause their hallucinogenic and plastogenic effects, and whether those effects are intertwined. To explore this question, we synthesized a library of psychedelic compounds containing an alkyne which, when combined with the powers of click chemistry, would allow us to identify and isolate protein targets, visualize binding in cells utilizing fluorescent probes, and test for covalent modification of histones as a reason for their long-lasting effects. Our initial library of compounds was based on LSD, 5-MeO-DMT, and 5-HT. To evaluate how structural modifications affect binding, the alkyne was appended onto one of the three most chemically accessible sites, for a total of 9 analogs. Then, using our 5HT2A-based biosensor, psychLight, we confirmed that our analogs bind and activate the 5-HT2A receptor with similar potency to the parent compounds. Our current studies are focused on treating, then imaging, cells, neurons, and brain tissue as a way to see localization of the compounds and elucidate psychedelics targets. Improving Hair Cortisol Analysis Efficiency and Reliability in Non-Human Primates: A Focus on Small Samples

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