Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons
Journal of Neurochemistry February 28, 2025 Aneta Petrušková, Debarpan Guhathakurta, Enes Yağız Akdaş et al. 8 citations
Serotonergic psychedelics like psilocybin, LSD, and DMT rapidly alter how neurons communicate at synapses. Using live-cell imaging in rat cortical neurons, the drugs reduced the fraction of synaptic vesicles that fuse in response to electrical stimulation within minutes, an effect that faded within 24 hours. DMT only reduced the total recycling pool of vesicles, while LSD and psilocin also shrank the readily releasable pool. Psilocin and DMT increased evoked glutamate release, yet LSD and psilocin lowered presynaptic calcium levels. Psilocin further depressed responses to paired stimuli. These drug-specific modulations of glutamatergic transmission may help explain their distinct therapeutic properties.