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Article

Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels

Department of Neurochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Cracow, Poland
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Author to whom correspondence should be addressed.
Academic Editors: Maurizio Bifulco and Simona Pisanti
Pharmaceuticals 2021, 14(10), 964; https://doi.org/10.3390/ph14100964
Received: 24 August 2021 / Revised: 17 September 2021 / Accepted: 22 September 2021 / Published: 24 September 2021
Systems pharmacology employs computational and mathematical methods to study the network of interactions a drug may have within complex biological pathways. These tools are well suited for research on multitarget drugs, such as natural compounds, in diseases with complex etiologies, such as osteoarthritis (OA). The present study focuses on cannabidiol (CBD), a non-psychoactive constituent of cannabis, targeting over 60 distinct molecular targets as a potential treatment for OA, a degenerative joint disease leading to chronic pain with a neuropathic component. We successfully identified molecular targets of CBD that were relevant in the context of OA treatment with both beneficial and detrimental effects. Our findings were confirmed by in vivo and molecular studies. A key role of PPARγ in mediating the therapeutic potential of CBD was revealed, whereas upregulation of multiple transient receptor potential channels demasked CBD-induced heat hyperalgesia. Our findings pave the way for novel CBD-based therapy with improved therapeutic potential but also encourage the use of bioinformatic tools to predict the mechanism of action of CBD in different conditions. We have also created an accessible web tool for analogous analysis of CBD pharmacology in the context of any disease of interest and made it publicly available. View Full-Text
Keywords: cannabidiol; osteoarthritis; chronic pain; neuropathic pain; systems pharmacology cannabidiol; osteoarthritis; chronic pain; neuropathic pain; systems pharmacology
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MDPI and ACS Style

Mlost, J.; Kędziora, M.; Starowicz, K. Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels. Pharmaceuticals 2021, 14, 964. https://doi.org/10.3390/ph14100964

AMA Style

Mlost J, Kędziora M, Starowicz K. Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels. Pharmaceuticals. 2021; 14(10):964. https://doi.org/10.3390/ph14100964

Chicago/Turabian Style

Mlost, Jakub, Marta Kędziora, and Katarzyna Starowicz. 2021. "Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels" Pharmaceuticals 14, no. 10: 964. https://doi.org/10.3390/ph14100964

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