Structural basis of LSD signaling

Published on July 31, 2019   31 min

Other Talks in the Series: G Protein-Coupled Receptors (GPCRs) Signaling in Health and Disease

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Hello everyone, and thank you for listening in to my talk. My name is Daniel Wacker, I am currently an Assistant Professor in the Department of Pharmacological Sciences and the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. I'm mostly interested in molecular studies of psychoactive drugs, and so the talk that I'll be giving today will be about the structural basis of LSD signaling.
So on Slide 2, I outline the talk in a little bit of detail. I will start out with giving a brief introduction into the history, the effects and the potential future applications of LSD, before we'll go into their molecular targets which psychedelics usually act via G protein-coupled receptors or GPCRs, and elicit cellular signals that then ultimatively cause the physiological responses. So our studies are mostly on these structural and functional aspects of LSD, and in particular, I will be talking about the detailed interactions between chemical LSD and its receptors, and what the pharmacological properties of LSD signaling are in molecular detail, how it elicits the types of signals it elicits, and lastly, what are the molecular mechanisms of LSD's long-lasting psychedelic effects. That's something that's been known for some time, but the underlying molecular principles haven't been known until we've elucidated the structure. Then I will very briefly summarize my talk, and provide a brief overview of the future directions of this type of research.
So LSD was originally synthesized and discovered by this Swiss chemist, Albert Hofmann in 1938 working in Switzerland at the time, and it was more of a serendipitous find of what LSD actually caused. So it was a chemical synthesized as a series of derivatives and originally, it was termed LSD-25 because it was the 25th in a series of lysergic acid derivatives. So what I've shown here on the left, is the chemical structure of LSD. I will go a little bit more into detail later on. So Albert Hofmann discovered the psychedelic effects of LSD in April 16,1943, which was effectively the day where he opened the vial and I think spilled a little bit of LSD on himself, and on his way home, he noticed what is now known as an altered state of conscious. So he experienced effectively the first LSD trip in history. A few days later, he repeated this experiment, so to speak, with a much larger dose of LSD in the state to this day known as Bicycle Day.