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

Abstract

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.

Cannabidiol usage, efficacy, and side effects: analyzing the impact of health conditions, medications, and cannabis use in a cross-sectional online pilot study

“…Research on CBD’s potential to treat anxiety disorders has shown promising results, with small randomized controlled trials indicating its anxiolytic effects ( 23 ). The exact mechanisms underlying the impact of CBD on the body remain unclear; however, they interact with serotonin receptors and modulate CB1 receptor activation, potentially influencing anxiety-related brain structures ( 4 , 24 ). The results regarding the effects of CBD on sleep are inconsistent, with studies showing varied outcomes ( 25 , 26 , preprint; 27 , 28 ).…”

Oral capsules of tetra‐hydro‐cannabinol (THC), cannabidiol (CBD) and their combination in peripheral neuropathic pain treatment

“…In our opinion, the study medication did comprise the essential components of cannabis, that is, THC and CBD, alone or in combination. These components have the potential to interact with relevant receptors such as CB1, CB2 and TRPV1 receptors, and exert other relevant actions all of which in experimental studies have been linked to the pain‐relieving action of cannabis (Finn et al, 2021, Mlost et al, 2021). It has been proposed that for the full effect of cannabis to be exerted, all or a large range of the more than 200 different components of cannabis, which besides CBD and THC, also includes minor components with interaction with cannabinoid receptors as well as a range of terpenes, are needed.…”