Tolerance must occur?Specifically, not the serotonin receptors that LSD binds to in the claustrum region of the brain. “Once LSD gets in the receptor, you can think of it as a hole in the ground. LSD jumps into it and then pulls a lid down over the top,” says study co-author Bryan Roth, a pharmacologist at the University of North Carolina at Chapel Hill School of Medicine. “Basically, from the structure we could tell that once LSD gets in there it can't get out. That's why it lasts so long.” We’re talking 12, 18, maybe 24 hours, by the way. Still, that lid will move around, so some LSD molecules will escape as the high wears off.