Paper. Estay-Olmos C, Morales-Weil K, Ahumada J et al.. Frontiers in Pharmacology, 7 Oct 2026.
Tags: Depression.
Psilocybin's synapse remodeling and its head-twitch response run through different cells.
Deleting 5-HT2A from cortical layer 5 pyramidal neurons abolished psilocybin-induced synapse formation and pruning in mice but left the head-twitch response untouched; restoring it there was sufficient. A second paper finds 5-HT1B receptors on forebrain excitatory neurons are required for psilocybin's post-acute anxiolytic effect but not its acute behavioural effects.
How much weight it carries: Cell-type-specific mouse genetics with clean necessity and sufficiency tests; says nothing directly about human hallucination or clinical benefit. (Mice, Preclinical, Mechanism, Controlled, Peer reviewed)
