Exposure to LSD alters the abundance of hundreds of proteins in lab-grown human brain tissue, affecting pathways related to protein quality control, energy metabolism, and the brain's ability to rewire itself. Mass spectrometry revealed changes in protein synthesis, folding, and degradation, as well as in glycolysis and oxidative phosphorylation. Follow-up experiments showed that LSD also promotes the growth of neuronal extensions, supporting its influence on neuroplasticity. These molecular changes may help explain how psychedelics could produce therapeutic effects in neuropsychiatric disorders.
Proteomic analysis of human cerebral organoids reveals that lysergic acid diethylamide (LSD) alters proteins involved in proteostasis, energy metabolism, and neuroplasticity-related pathways. LSD exposure changed protein synthesis, folding, autophagy, and proteasomal degradation, suggesting complex regulation of neural cell function. It also modulated glycolysis and oxidative phosphorylation, which are crucial for cellular energy management and synaptic function. Complementary experiments showed LSD enhanced neurite outgrowth in vitro, confirming its impact on neuroplasticity. These findings provide insight into molecular mechanisms through which LSD may affect neuroplasticity and potentially contribute to therapeutic effects for neuropsychiatric disorders.