Lysergic acid diethylamide (LSD), considered the prototypical psychedelic molecule, has effects on consciousness and perception. However, the molecular mechanisms involved in LSD effects in human neural cells and how they may be translated into changes in physiology are still poorly understood. Here we used human cerebral organoids as a biological live model to explore the response of human brain cells to LSD. Mass spectrometry-based proteomics was performed to gain insights on molecular targets and signaling pathways involved in the mid and long-term effects of LSD.