Enhancing plasticity to treat depression and other central nervous system diseases using event-driven pharmacology.
Journal of psychopharmacology (Oxford, England) July 13, 2026 Todd D Gould, Sanjay J Mathew, Maurizio Fava et al.
A new pharmacological model called event-driven pharmacology (EDP) is described, in which a plastogen—a drug that induces lasting neural plasticity—produces sustained effects after only transient binding, unlike traditional drugs that require continuous receptor occupancy. Plastogens such as ketamine and classical psychedelics can trigger metaplasticity, priming synapses to respond to later stimuli long after the drug has left the body. Dosing such drugs to maintain constant target occupancy may paradoxically reduce benefits and increase side effects. The EDP model calls for new drug development, dosing strategies, and biomarkers to harness the therapeutic potential of plastogens for depression and other synaptic disorders.