The grid parameter was generated covering the CB1 pockets for (PDB:7V3Z) [-42.91, -163.58, 306.7], (PDB:5U09) [126.7,118.85,147.7], (PDB:6KQI) [-25.98, -8.77, 40.11] for x,y,z coordinates. The ligand diameter midpoint box follows a 10Å x 10Å x 10Å x,y,z dimension. The grid parameter was generated covering the CB2 pockets for (PDB:5ZTY) [9.09, -0.17, -55.72] for x,y,z coordinates. The Ligand diameter midpoint box follows a 10Å x 10Å x 10Å x,y,z dimension. The grid parameter was generated covering the GPR119 pocket (PDB:7WCM) [126.7, 118.85, 147.7] for x,y,z coordinates. The ligand diameter midpoint box follows a 10Å x 10Å x 10Å x,y,z dimension. The grid parameter was generated covering the PAK1 pocket (PDB:5DFP) .61] for x,y,z coordinates. The ligand diameter midpoint box follows a 10Å x 10Å x 10Å x,y,z dimension. The grid parameter was generated covering the PPAR-γ pocket (PDB:2P4Y) [35.4, -21.89, 39.56_B] for x,y,z coordinates. The ligand diameter midpoint box follows a 10Å x 10Å x 10Å x,y,z dimension. Prepared proteins were produced by the protein preparation workflow tool on the Maestro 13.8 interface of Schrödinger Protein Preparation Wizard . Prime MM-GBSA (MMGBSA dG Bind (NS) and MMGBSA dG Bind) energy was calculated and displayed in Table -SI. MM/GBSA calculations were accomplished to esteem the relative binding energies of cannabinoids to the receptors.