Evaluation of cannabis-derived anti-inflammatory and analgesic treatment in animals and identification of cannabinoid-based effective inhibition of prostaglandin through computational studies

Many medical conditions are accompanied by severe pain. Acute pain refers to the experience of pain that lasts for only a few hours, whereas chronic pain is the ongoing emergence of pain signals over an extended period. Since ancient times, cannabis has been utilized for medical purposes. This article demonstrates the medicinal importance of cannabinoids through their analgesic and anti-inflammatory activities. Additionally, the mechanisms of cannabinoid-induced analgesia have been interpreted via preclinical investigations in animals. Cannabinoid extracts were formulated into gel and cream at concentrations of 2.5% and 5%. The cannabis cream showed the highest analgesic activity at 5% compared to methyl salicylate as a control. Moreover, cannabis gel produced a comparable anti-inflammatory effect at 5% against the standard diclofenac sodium. Molecular docking studies of all cannabinoids were performed to understand their modes of interaction and binding affinities with the cyclooxygenase II receptor. Additionally, molecular dynamics simulation studies were conducted for for both the ligand-free and cannabidiol-bound cyclooxygenase II to validate the <i>in vivo</i> and molecular docking results. During simulations, the stability of the protein was analyzed using root-mean-square deviation and root-mean-square fluctuation. The study of trajectories of the ligand-free and ligand-bound proteins was assessed using radius of gyration and solvent accessible surface area. Molecular mechanics/generalized Born surface area was used to evaluate the free energies of ligand binding. Dynamic cross-correlation matrix, principal component analysis and free energy landscape characterized the conformational changes and relative energies of them, which shows the existence of two metastable conformations in cyclooxygenase II, one of which is possibly the native state with catalytic activity. In conclusion, the data from this study support the use of medicinal cannabis in the management of pain. To mitigate the suffering of patients experiencing extreme pain, the rational use of cannabis-based drugs merits significant consideration.