Nature Structural & Molecular Biology
June 22, 2026
Qianru Jiang, Jianming Han, Eve Fine et al.
Ketamine offers rapid relief for treatment-resistant depression and severe pain in the clinic, providing immediate benefits that traditional medications often fail to deliver. While its antagonistic action at the N-methyl-D-aspartate receptor (NMDAR) is a key mechanism, ketamine's dual nature as both a promising treatment and a drug with abuse potential suggests its therapeutic effects extend...
UNC Libraries
June 7, 2024
Kami Kim, Tao Che, Ouliana Panova et al.
Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions—both therapeutic and hallucinogenic—are not understood, although activation of...
Nature
May 1, 2023
Jianming Han, Jingying Zhang, Antonina L. Nazarova et al.
79 citations
The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorders1. However, the development of KOR analgesics has been hindered by the associated hallucinogenic side effects2. The initiation of KOR signalling requires the Gi/o-family proteins including the conventional (Gi1, Gi2, Gi3, GoA and GoB) and...
Nature
September 28, 2022
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim et al.
There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally 1 – 4 . Efforts have focused on readily synthesizable molecules, inevitably leaving many chemotypes unexplored. Here we investigate structure-based docking of a bespoke virtual library of tetrahydropyridines—a scaffold that is poorly sampled by a general...
Cell
January 26, 2017
Daniel Wacker, Sheng Wang, John D. Mccorvy et al.
466 citations
SUMMARY The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slowly from both...