The 5-HT(2A) serotonin receptor, abundant in cortical pyramidal neurons and targeted by hallucinogens and psychiatric medications, is present in a subset of dendritic spines and colocalizes with PSD-95 and MUPP1. Activation by the agonist DOI transiently increases spine size and phosphorylates PAK, a downstream target of kalirin-7. Peptide interference preventing kalirin-7 localization to the postsynaptic density disrupts DOI-induced PAK phosphorylation and spine morphogenesis. These findings suggest serotonin signaling may modulate dendritic spine morphology through kalirin-7 at cortical synapses.
Setting up a psychedelic study is a long and complex process that presents unique challenges not yet standardized. This review brings together major UK research teams to formalize these considerations, identify ongoing debates, and provide a practical guide for researchers and policymakers. It addresses challenges to existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. The paper can be read end-to-end or used as a manual with sections for specific needs.