Our results revealed diverse interactions between cannabinoids and both CB1 and CB2 receptors, including hydrogen bonding and π-stacking interactions. Compound 2 exhibited the lowest binding energy (-10.63 kcal/mol) with CB1, indicating a strong affinity. Interestingly, compound 5 formed the most stable ligand-protein complex with CB2. These findings suggest the potential of cannabinoids to modulate cannabinoid receptors, which play crucial roles in pain modulation, appetite regulation, and immune function.