It is unclear how psilocybin exerts its therapeutic effects, but most studies have presumed that the serotonergic 5HT2A receptors, which are responsible for most of the psychedelic effects, play a key role. A recent rodent study suggests otherwise. In this video, I will give a quick perspective on this interesting study and discuss some of its limitations from a neuropharmacology perspective.
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Further reading:
Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice
Natalie Hesselgrave, Timothy A Troppoli, Andreas B Wulff, Anthony B Cole, Scott M Thompson
PMID: 33850049 DOI: 10.1073/pnas.2022489118
Antidepressant drugs act by directly binding to TRKB neurotrophin receptors
Plinio C Casarotto, Mykhailo Girych, Senem M Fred, Vera Kovaleva, Rafael Moliner, Giray Enkavi, Caroline Biojone, Cecilia Cannarozzo, Madhusmita Pryiadrashini Sahu, Katja Kaurinkoski, Cecilia A Brunello, Anna Steinzeig, Frederike Winkel, Sudarshan Patil, Stefan Vestring, Tsvetan Serchov, Cassiano R A F Diniz, Liina Laukkanen, Iseline Cardon, Hanna Antila, Tomasz Rog, Timo Petteri Piepponen, Clive R Bramham, Claus Normann, Sari E Lauri, Mart Saarma, Ilpo Vattulainen, Eero Castrén
PMID: 33606976 PMCID: PMC7938888 DOI: 10.1016/j.cell.2021.01.034
NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Panos Zanos, Ruin Moaddel, Patrick J Morris, Polymnia Georgiou, Jonathan Fischell, Greg I Elmer, Manickavasagom Alkondon, Peixiong Yuan, Heather J Pribut, Nagendra S Singh, Katina S S Dossou, Yuhong Fang, Xi-Ping Huang, Cheryl L Mayo, Irving W Wainer, Edson X Albuquerque, Scott M Thompson, Craig J Thomas, Carlos A Zarate Jr, Todd D Gould
PMID: 27144355 PMCID: PMC4922311 DOI: 10.1038/nature17998
