Science

Why an LSD high lasts for so long

“By freezing an LSD molecule bound to a single brain cell receptor as a crystal in a lab, researchers were able to get a 3-D x-ray image of the drug and the protein locked together…It is the first 3-D image of a psychedelic bound to a brain receptor, Roth says.”

“My lab has been trying to do this since the early 1990s,” says Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill and senior author on the paper. “I remember Dan Wacker [a co-author, also at U.N.C.] showing the image. It was basically a moment of silence. I started to fight back tears of gratitude that we had finally gotten it.”…The image showed Roth and his co-authors something strange about the way LSD fit inside this receptor. Drugs typically come and go from receptor proteins like ships pulling in and out of a port. But when an LSD molecule lands on the receptor, the molecule snags onto a portion of the protein and folds it over itself as the molecule binds to the receptor….“There was this lid that came over the molecule. It looked like it trapped LSD in the receptor,” Roth says. “That immediately suggested to us why LSD lasts so long.”…LSD seems to stimulate the receptor for the entire time it is trapped underneath the protein “lid,” Roth says. Proteins are in constant motion, so he thinks the lid eventually flops open, allowing the drug to fly out and the effects to wear off. But the team ran computer models that suggest it could take hours for that to happen. Until then, the trip goes on….Roth’s experiments also suggest that the longer LSD stimulates the receptor, the more powerful the effects become. “What we show in the paper is that LSD becomes a hundred times to a thousand times more potent [after a few hours],” Roth says. “It begins to explain not only why standard recreational doses have this profound effect, but also why microdoses (about 10 micrograms of LSD) might have an effect.”

Original Article (PBS):
Why an LSD high lasts for so long
Artwork Fair Use: Robert Huber at English Wikibooks

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