Towards Better Therapeutics for Depression with Cannabidiol (CBD)

Depression is a debilitating and highly prevalent disease. Despite many antidepressants available, they all present a delayed therapeutic effect and are not effective in about 40% of patients (treatment-resistant depression - TRD); except for ketamine, which holds potential for abuse and dependence. Thus, research into new drugs with a faster onset of action and which can successfully treat TRD is an urgent unmet medical need. cMOOD will investigate a promising intervention, Cannabidiol (CBD) - the main non-psychotomimetic component of cannabis. We have previously shown that CBD triggers rapid AD effect and herein I will test it in TRD using a translational approach, combining animal models with state-of-the-art techniques. Furthermore, we will investigate if CBD effects are due to the binding to the cholesterol recognition site in the Tropomyosin receptor kinase B (TRKB.CARC) and rapid modulation of neurotrophin signalling and neuroplasticity, recently suggested a mechanism to the AD effect. Based on our supporting preliminary findings, cMOOD will elucidate: a) Pharmacodynamic properties of CBD binding to TRKB.CARC and effects on neurotrophin signalling, neuroplasticity and behaviour; b) Molecular fingerprinting and neurocircuitry associated with TRD and the AD effect. cMOOD will, thus, demonstrate CBD
AD properties by providing mechanistic evidence for its effect and will unravel novel molecular targets to pave the way for better treatment options.