Electrophysiological mechanisms of psychedelic drugs: A systematic review.
Neuroscience and biobehavioral reviews June 1, 2026 Javier Hidalgo Jiménez, Karl Kristjan Kaup, Jaan Aru 1 citation
Psychedelics such as LSD and NBOH produce complex, heterogeneous effects on brain cells, challenging the idea that they simply increase cortical excitability. A systematic review of 23 in vitro and 26 in vivo electrophysiological studies found that these compounds modulate both excitatory and inhibitory processes in a cell-type- and compartment-specific manner, with biphasic, dose-dependent, and context-sensitive responses. Activation of 5-HT2A receptors triggers intricate calcium signaling, downregulating excitatory currents and firing rates in many neurons while enhancing glutamate release and activating a subset of projection fibers. Modulation of presynaptic and extrasynaptic GluN2B-containing NMDA receptors appears central to these effects.