Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics
Trends in Pharmacological Sciences September 24, 2021 Lily R. Aleksandrova, Anthony G. Phillips 255 citations
Ketamine and classical psychedelics (psilocybin, LSD, and DMT) work as fast-acting antidepressants by promoting neuroplasticity. Evidence from preclinical and clinical studies shows these compounds trigger synaptic, structural, and functional changes, especially in pyramidal neurons of the prefrontal cortex. They increase glutamate release, activate AMPA receptors, and stimulate BDNF and mTOR signaling, leading to the expression of synaptic proteins and synaptogenesis. This adaptive rewiring of pathological neurocircuitry may explain their robust and sustained therapeutic effects.