Lysergic acid diethylamide (LSD) has been credited, in part, for the creation of the iPhone, the polymerase chain reaction, as well as some pretty abstract artwork. Since the drug is classified as a Schedule 1 substance in the U.S., it’s been more difficult for scientists to legally study the drug and learn about how it affects the brain. Therefore, when a study (or two) is published it makes the findings all the more fascinating. Two studies were published last week (one in Current Biology, the other in Cell) that examine how LSD produces such diverse effects and why the drug takes so long to wear off. The Scientist reports the findings from for the first study: For the Current Biology study, 21 volunteers were given a placebo, a small dose of LSD alone, or the same dose of LSD but with kentaserin, a serotonin 2A antagonist. Study participants who took the kentaserin reported virtually the same experiences as those who took the placebo, and fMRI brain scans confirmed similar brain activities across participants in both groups. The serotonin 2A antagonist “blocked all the effects of LSD, so it was like if people didn’t take any drugs,” coauthor Katrin Preller, neuroscientist at the Zurich University Hospital in Switzerland told The Verge. “All the typical symptoms — hallucinations, everything — were gone.”
As for why an LSD high lasts for so long, Angus Chen has written an in-depth report on PBS Newshour about the findings from the study published in Cell: LSD and other psychoactive drugs work by binding to specialized proteins called receptors on the surfaces of neural cells. On the receptor protein is a sculpted “pocket,” into which molecules with the right shape can fit and thus stick to the cell, where they initiate changes in the brain. But different substances can often fit into the same receptor. Many receptors that bind LSD and DMT, for example, also fit the natural chemical messenger serotonin — which is produced in the body and helps regulate mood. Figuring out how each drug interacts with the same receptor in a different way is key to understanding why an LSD trip lasts all day whereas an experience with extracted DMT is often over in 15 minutes or less. 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. The image showed Bryan Rother, a pharmacologist at the University of North Carolina at Chapel Hill and senior author on the paper, 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. 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.

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Source: Slashdot – Why An LSD High Lasts For So Long