Cell
January 26, 2017
Daniel Wacker, Sheng Wang, J. Mccorvy et al.
466 citations
The hallucinogen LSD binds to the human serotonin receptor 5-HT2B, and its crystal structure reveals conformational rearrangements that accommodate LSD, explaining the selectivity of its diethylamide group. LSD dissociates very slowly from both 5-HT2BR and 5-HT2AR, a key receptor for its psychoactive effects. Molecular dynamics simulations suggest that a 'lid' formed by extracellular loop 2 (EL2) at the binding pocket entrance may cause LSD's slow binding kinetics. A mutation that increases this lid's mobility greatly speeds up LSD's binding and selectively reduces LSD-mediated β-arrestin2 recruitment, providing a molecular explanation for LSD's actions at human serotonin receptors.
Drug Testing and Analysis
June 6, 2016
S. Brandt, P. Kavanagh, F. Westphal et al.
62 citations
Two new psychoactive substances, AL-LAD and LSZ, which are analogs of LSD, were analytically characterized using multiple techniques including NMR, mass spectrometry, and infrared analysis. In male mice, both compounds produced LSD-like behavioral responses in a head-twitch assay, with dose-dependent effects peaking at 200 µg/kg. LSZ was equipotent to LSD (ED50 = 114.2 nmol/kg vs. 132.8 nmol/kg), while AL-LAD was slightly less potent (ED50 = 174.9 nmol/kg). The direct translation of these potency comparisons to humans requires further study. Providing chemical and pharmacological data on emerging substances aids research communities focused on substance use and forensic identification.
Drug Testing and Analysis
May 10, 2017
S. Brandt, P. Kavanagh, F. Westphal et al.
44 citations
Two new lysergamides, ETH-LAD and 1P-ETH-LAD, were characterized using multiple analytical techniques including GC-MS, mass spectrometry, infrared analysis, HPLC, and NMR. 1P-ETH-LAD had not previously been described in scientific literature. When incubated with human serum at 37°C, 1P-ETH-LAD converted to ETH-LAD over time, suggesting it may act as a pro-drug. 1P-ETH-LAD remained detectable in serum after 24 hours. This work provides analytical data for clinicians and toxicologists who may encounter these substances on the new psychoactive substances market.