Why LSD lasts 12 hours.

[Intrepid_traveler]

I'm sure we have all wondered of LSD:
"How can a compound which is cleared from the blood stream in a matter of hours produce such long lasting effects?"

Well, the research below might help clear things up:

Scientists from Roth's lab at UNC captured crystallography images (images showing how a molecule's atoms are arranged) of an LSD molecule bound to a human serotonin receptor and discovered that the LSD molecule was wedged into the receptor's binding pocket at an angle no one had expected. On top of that, part of the receptor protein had folded in over the LSD like a lid, sealing the drug inside.

"Once LSD gets in the receptor, a lid comes over the LSD, so it's basically trapped in the receptor and can't get out," says Roth. "LSD takes a really long time to get on the receptor, and then once it gets on, it doesn't get off," he added.

This finding explains why LSD trips last for a full day, even though LSD doses are extremely small -- the average dose is 100 or so micrograms -- and LSD molecules are cleared from the bloodstream in a couple of hours. Given that there has been a tentative resurgence in testing LSD for some medical conditions, understanding the mechanism of its potent and long-lasting actions may help drug developers design more effective psychiatric drugs with fewer side effects, the researchers say.
https://www.sciencedaily.com/releases/2017/01/170126132541.htm

Its funny, isomers of LSD such as iso-lysergic acid diethylamide are inactive, this is due to an asymmetric carbon atom at position 8, so the carbonyl with the diethylamide grouping attached at position 8 can be facing different directions in space, hence hitting the receptor site in a different way. When the carbonyl-diethylamide grouping at position 8 is facing away from the receptor site, as with iso-LSD, you get inactivity.

I'm positive that the article above is referring to the way in which the diethylamide moiety at position 8 of the LSD molecule hits the receptor site.

I never realized that the carbonyl-diethylamide grouping at position 8 was "locking" the molecule into the receptor site, and was always curious as to how LSD could produce such long duration experiences...

fascinating stuff!