Lsd Crystal

Psychedelic drugs such as lysergic acid diethylamide (LSD) show promise in the treatment of depression and substance abuse disorders, but chemists still don’t know how they work at a molecular level. Now, a team led by Bryan Roth, a molecular pharmacologist at the University of North Carolina at Chapel Hill School of Medicine, has produced the first crystal structure of a psychedelic compound bound to its receptor in the active state. Using X-ray crystallography and cryo-electron microscopy, the researchers determined the structures of LSD Crystal and other hallucinogenic compouds bound to the 5-HT2A serotonin receptor (HTR2A) (Cell 2020, DOI: 10.1016/j.cell.2020.08.024). These protein structures show how the molecules “dive into the core of the receptor and cause a tryptophan residue to be dislocated extensively—more than we had ever imagined,” Roth says. “It gives us the first molecular insights into psychedelic drug action.” The team is developing tools to screen new drug candidates for their ability to activate the receptor without causing hallucinogenic side effects.

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