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 research study involves a long, arduous, and Kafkaesque process with many unstandardised challenges. These complexities challenge existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. This review brings together major UK psychedelic research teams to formalise these unique considerations, addressing sociocultural, political, legal, pharmacological, safety, study design, and experiential facets. It identifies continuing areas of debate and provides a practical, experience-based guide with recommendations for policymakers and future researchers intending to set up a psychedelic study or clinical trial.
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.