A single dose of psilocybin, a psychedelic whose metabolite psilocin activates 5-HT2A receptors, induces long-term genetic and functional changes in neurons of the orbitofrontal cortex (OFC), a brain region implicated in depression and other psychological disorders. Excitatory and inhibitory neurons together reduce circuit activity in the OFC. Knocking down the 5-HT2A receptor in deep-layer excitatory neurons diminishes these functional changes and the anti-depressant effect. These findings reveal cell type-specific mechanisms of psilocybin and highlight differences in how psychedelics affect distinct brain regions.
Low-dose esketamine may reduce the incidence of intraoperative hypoxaemia during non-intubation thoracoscopic surgery. This randomized controlled trial will assign patients to receive either esketamine or a placebo (normal saline). The main outcomes are the occurrence of hypoxaemia (oxygen saturation ≤90% for at least 10 seconds) and the time until it appears. Secondary outcomes include hypercapnia, inflammatory markers, pain scores, recovery times, and complications. The trial is registered and approved by an ethics committee.