A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics

Ketamine and serotonergic psychedelics like psilocybin both relieve depression and promote neural plasticity, despite targeting different molecular receptors. This opinion article proposes a conceptual framework suggesting their actions converge at the dendrites, where they both enhance and suppress membrane excitability. Mismatches in these opposing effects may explain differences in cell-type and region selectivity, the compounds' moderate range of effects and toxicity, and their plasticity-promoting capacities.

Study at a glance

Abstract

Pilot studies have hinted that serotonergic psychedelics such as psilocybin may relieve depression, and could possibly do so by promoting neural plasticity. Intriguingly, another psychotomimetic compound, ketamine, is a fast-acting antidepressant and induces synapse formation. The similarities in behavioral and neural effects have been puzzling because the compounds target distinct molecular receptors in the brain. In this opinion article, we develop a conceptual framework that suggests the actions of ketamine and serotonergic psychedelics may converge at the dendrites, to both enhance and suppress membrane excitability. We speculate that mismatches in the opposing actions on dendritic excitability may relate to these compounds' cell-type and region selectivity, their moderate range of effects and toxicity, and their plasticity-promoting capacities.