The effect of psilocybin on depression symptom severity, peripheral biomarkers and synaptic density – a single dose randomized double blind, placebo-controlled phase 2 PET study

Despite the large implications of Major Depressive Disorder (MDD) on disease burden worldwide, current treatment options are suboptimal and about a third of patients suffering from MDD do not respond to treatment.

Therefore, an unmet need exists for the development of new treatment options and methods to aid appropriate treatment selection in individual patients. Recent clinical data indicate one single dose of psilocybin to have rapid and long lasting clinical effects.

Animal model data suggest this to be mediated via 5-HT, KYNA and BDNF, and associated with synaptogenesis in hippocampus.

Here these questions are adressed in MDD patients for the first time.We will explore the antidepressant effect of a single dose of psilocybin in an randomized placebo controlled phase 2B trial in 30 patients.

We will use [11C]UCB-J Positron Emission Tomography (PET) to quantify a marker for synaptic density in brain in vivo, and related peripheral biomarkers in blood and CSF (p11 in PBMCs using FACS; BDNF in plasma using western blot; 5-HT and 5-HT metabolites in CSF using HPLC; kynuerine acid and metabolites in plasma and CSF using LC/MS)  before and after treatment.

The clinical effect will be followed from one day after dose up to one year after dosing.

Relevant safety parameters will be followed.The clinical trial take place at Norra Stockholms Psykiatri, SLSO, in collaboration with KI, which is responsible for PET and analysis of PBMCs, plasma and CSF. The project will run 2021-2025.