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

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.

Automated summary

Studies have shown that serotonergic psychedelics like psilocybin and ketamine may relieve depression by promoting neural plasticity. Despite targeting distinct molecular receptors in the brain, the behavioral and neural effects of these compounds are similar, possibly by enhancing and suppressing membrane excitability at dendrites.