Cannabigerol and Cannabinoid Receptors in Major Depressive Disorder: Network Pharmacology, Molecular Docking, and...

Cannabigerol (CBG), being one of the non-psychotropic phyto-cannabinoid, has been labelled and recognized to be antioxidant and neuroprotective; it may conceivably hold depression-relieving activity. Consequently, the objective of the present research procedure was to explore the depression-alleviating competence of cannabigerol in both stressed and unstressed mice using computational/in-silico modelling, followed by in-vivo analysis.

Target genes for Major Depressive Disorder (MDD) were identified using GeneCards and Swiss Target Prediction, with common targets screened via Venny software. STRING database analysis established protein-protein interactions (PPI), identifying CNR2 (CB2 receptor) as a key target. Molecular docking of CBG with CB2 (PDB ID: 8GUR) showed strong binding, prompting in-vivo evaluation. ADME profiling via Schrödinger Maestro v10.5 confirmed CBG's high oral absorption and favorable pharmacokinetics. Male Swiss albino mice underwent chronic unpredictable mild stress (CUMS) for three successive weeks, with CBG (10, 20, 40 mg/kg) and imipramine (15 mg/kg) administered and various behavioral and biochemical parameters being analyzed.

Cannabigerol demonstrated maximum oral absorption in ADME predictions using Schrödinger's Maestro (v10.5). Wayne diagram illustrated MDD-related targets, with CB2 (CNR2) rankings in top targets, based on SwissADME and Venny software analysis. Docking analysis revealed a high binding affinity (-10.53) for CB2, outperforming cannabidiol (-9.56) and comparable to Δ9-THC (-10.11). During in-vivo evaluation, CBG (40 mg/kg) and Imipramine 15 mg/kg significantly reduced CUMS-induced exalted plasma corticosterone, nitrite quantities, and monoamine oxidase-A action in the brain of stressed mice. Additionally, both treatments substantially reversed the unpredictable chronic stress-induced decline in catalase action, demonstrating CBG's possible potential in alleviating depression-like symptoms in mice.

Cannabigerol has shown significant depressive alleviating potential in mice exposed to chronic and unpredictable stress regimes, possibly via interaction with cannabinoid receptors as indicated by in-silico modelling, which has been validated by our findings of the in-vivo protocol.