The effect of psilocybin on neural plasticity in major depressive disorder

This project will evaluate the effect of psilocybin on neural plasticity in patients with major depressive disorder (MDD).

Psilocybin is a substance that induces psychedelic experiences, and preliminary evidence suggests that it can be an effective treatment for severe MDD.

Psilocybin is both a novel and controversial candidate therapeutic for depression, and the in vivo biological effects of the drug are largely unknown.

One hypothesis is that psilocybin augments synaptic connections in key brain regions, and restores neural plasticity in patients with MDD.This project aims to investigate changes in synaptic density, a biomarker for neural plasticity, following an oral dose of psilocybin.

First, we will establish a protocol for analyzing synaptic density, using the imaging modality positron emission tomography (PET).

This protocol will be developed using data from healthy volunteers exposed to psilocybin in studies carried out at Rigshospitalet in Copenhagen.

Following evaluation on healthy controls, the analysis protocol will then be applied to MDD patients participating in a double-blind randomized placebo- controlled psilocybin study at Karolinska Institutet.The project has the potential to advance our knowledge about fundamental biological changes following exposure to psychedelic drugs in the healthy and diseased brain.

It will put the neuroplasticity hypothesis of MDD to the test, and can deliver a deeper understanding of depression treatments.