Psilocybin, ketamine, LSD, and even nitrous oxide (laughing gas) all disrupt the same overactive brain network through completely different receptor pathways, suggesting that quieting this network is the shared mechanism behind their antidepressant effects. A single psilocybin dose triggers new dendritic spine growth in the frontal cortex that persists for at least one month, offering a cellular explanation for why therapeutic effects outlast the drug by weeks or months. A landmark trial that administered ketamine to patients already under surgical anesthesia found that a significant portion of its antidepressant signal disappeared when the subjective high was blocked, directly implicating the conscious psychedelic experience as a key therapeutic ingredient rather than just the drug's chemistry.