Translational research investigating psilocybin: underlying neurobiological mechanisms

This dissertation has taken an interdisciplinary approach to investigate and give insights into psilocybin’s neurobiological underpinnings. Psilocybin is a naturally occurring serotonergic psychedelic and is the main ingredient in hallucinogenic mushrooms. Research has demonstrated that psilocybin profoundly activates the serotonin (5-hydroxytryptamine) 2A (5-HT2A) receptors. Upon activation of these receptors in the brain, psilocybin induces profound perceptual changes such as hallucinations and illusions, altering one’s self-perception, bodily image and mood. There is a growing interest in psilocybin’s therapeutic utility, focusing on psychiatric disorders, such as treatment-resistant depression. Despite psilocybin’s therapeutic potential, the underlying neurobiological mechanisms of psilocybin remain elusive. Therefore, this dissertation aimed to understand and delineate the acute dose-dependent effects of psilocybin on an epigenetic, neurobiological and cognitive level.