“Background: The bioactivity and potential medicinal applications of cannabiorcol, a lesser-known derivative of Cannabis sativa, require further investigation. Osteoarthritis (OA) is a chronic joint condition marked by gradual degradation of the cartilage and commonly associated with elevated levels of matrix metalloproteinases (MMPs). However, the influence of cannabiorcol on OA and its underlying mechanisms remains unclear.

Methods: In silico analysis investigated the key transcription factors that regulate MMP expression. A chondrocyte cell model [interleukin (IL)-1β and IL-1⍺-treated C20A4 cell line] was established and treated with cannabiorcol. Associated cytotoxicity was assessed using a WST-8 assay. A monoiodoacetate-induced OA rat model was established and treated with cannabiorcol. Protein translocation and transactivation analyses were conducted using immunofluorescence and dual-luciferase reporter assays, respectively. Western blotting and real-time PCR analyzed relevant markers to examine cannabiorcol’s effects on OA and its fundamental mechanisms.

Results: Cannabiorcol inhibits the expression of IL-1β-induced MMPs compared to other cannabis-related compounds. In silico analysis revealed that the nuclear factor-kappa β (NF-κβ) and mitogen-activated protein kinase (MAPK) pathways are associated with MMP expression as key regulators. In vitro, cannabiorcol inhibits the NF-κB and p38 MAPK pathways independently cannabinoid receptors and transient receptor potential vanilloids. In vivo, cannabiorcol reduces MMP expression and ameliorates monoiodoacetate-induced OA traits in rats.

Conclusion: Cannabiorcol inhibits IL-1β-induced MMP expression in vitro and alleviates OA in an MIA-induced OA rat model by reducing MMP expression and inhibiting the p65/p38 axis.”

https://pubmed.ncbi.nlm.nih.gov/39405610/

“Phytocannabinoids are naturally occurring compounds found in Cannabis sativa that are being investigated as potential therapeutic agents for various diseases. Our findings offer new perspectives on cannabiorcol’s therapeutic potential for OA treatment. Our study demonstrates the potential therapeutic effects of cannabiorcol in OA by inhibiting MMP expression and attenuating inflammatory pathways such as NF-κB and p38 MAPK. Hence, cannabiorcol may represent a promising candidate for further investigation and development of OA treatments.”

https://www.sciencedirect.com/science/article/pii/S0944711324007980?via%3Dihub

“Purpose, and design: Knee osteoarthritis (OA) is one of the most common and debilitating diseases, especially in the elderly. Hemp seed oil is a plant product that has been used as a food or drug since ancient times because of its anti-inflammatory and analgesic properties.

Methods: A double-blind, active, placebo-controlled trial was done to assess the efficacy of hemp seed oil on knee OA. Ninety patients were randomly allocated to three groups; hemp seed oil, diclofenac gel, and placebo via a blocked randomization method, and were asked to apply the topical treatment daily for 2 months. The study participant underwent assessments before, and four and 8 weeks after the intervention. Evaluation included measurements of the heel-to-thigh distance, utilization of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and application of visual analog scale (VAS). Data analysis was performed using SPSS.24 and the significance level was considered as p < .05.

Results: All parameters, except heel-to-thigh distance, improved significantly in the hemp seed oil group compared to placebo group. Improvements in VAS and WOMAC parameters were not different comparing the hemp seed oil and diclofenac gel groups. Heel-to-thigh distance decreased significantly within all groups during the study. There were no significant differences in improvements in heel-to-thigh distance comparing the three groups.

Conclusion, and clinical implications: Hemp seed oil led to greater improvements in VAS pain score and WOMAC parameters, but not knee flexion range, compared to placebo. There were no differences in measured outcomes comparing hemp seed oil and diclofenac gel.”

https://pubmed.ncbi.nlm.nih.gov/39256070/

https://www.painmanagementnursing.org/article/S1524-9042(24)00229-7/fulltext

“Hand osteoarthritis (OA) is an irreversible degenerative condition causing chronic pain and impaired functionality. Existing treatment options are often inadequate. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory effects in preclinical models of arthritis. In this open-label feasibility trial, participants with symptomatically active hand OA applied a novel transdermal CBD gel (4% w/w) three times a day for four weeks to their most painful hand. Changes in daily self-reported pain scores were measured on a 0-10 Numeric Pain Rating Scale (NPRS). Hand functionality was determined via daily grip strength measures using a Bluetooth equipped squeeze ball and self-report questionnaire. Quality of life (QoL) ratings around sleep, anxiety, stiffness and fatigue were also measured. All self-report measures and grip strength data were gathered via smartphone application. Urinalysis was conducted at trial end to determine systemic absorption of CBD. Eighteen participants were consented and 15 completed the trial. Pain ratings were significantly reduced over time from pre-treatment baseline including current pain (- 1.91 ± 0.35, p < 0.0001), average pain (- 1.92 ± 0.35, p < 0.0001) and maximum pain (- 1.97 ± 0.34, p < 0.0001) (data represent mean reduction on a 0-10 NPRS scale ± standard error of the mean (SEM)). A significant increase in grip strength in the treated hand (p < 0.0001) was observed although self-reported functionality did not improve. There were significant (p < 0.005) improvements in three QoL measures: fatigue, stiffness and anxiety. CBD and its metabolites were detected at low concentrations in all urine samples. Measured reductions in pain and increases in grip strength seen during treatment reverted back towards baseline during the washout phase. In summary, pain, grip strength and QoL measures, using smartphone technology, was shown to improve over time following transdermal CBD application suggesting feasibility of this intervention in relieving osteoarthritic hand pain. Proof of efficacy, however, requires further confirmation in a placebo-controlled randomised trial.Trial registration: ANZCTR public trials registry (ACTRN12621001512819, 05/11/2021).”

https://pubmed.ncbi.nlm.nih.gov/38783008/

“The current study suggests that transdermal CBD gel may have a beneficial effect on pain and grip strength in participants with symptomatic hand OA but requires further exploration in a randomised controlled trial. This pilot study contributes towards closing this evidence gap and demonstrates that transdermal CBD may provide some promise for a safe treatment option for symptomatically active hand OA.”

https://www.nature.com/articles/s41598-024-62428-x

“Cannabidiol (CBD) is a non-intoxicating cannabinoid from cannabis sativa that has demonstrated efficacious against inflammation, which can be considered as a potential drug for arthritis treatment. However, the poor solubility and low bioavailability limit its clinical application. Here, we report an effective strategy to fabricate CBD-loaded poly lactic-co-glycolic acid nanoparticles (CBD-PLGA-NPs), with a spherical morphology and an average diameter of 238 nm. CBD was sustained release from CBD-PLGA-NPs, which improved the bioavailability of CBD. The CBD-PLGA-NPs effectively protect the damage of LPS to cell viability. We observed that CBD-PLGA-NPs significantly suppressed LPS-induced primary rat chondrocyte expression of inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase 13 (MMP-13). Remarkably, CBD-PLGA-NPs also showed better therapeutic effects of inhibiting the degradation of the extracellular matrix of chondrocytes than equivalent CBD solution. In general, the fabrication CBD-PLGA-NPs showed good protection of primary chondrocytes in vitro and is a promising system for osteoarthritis treatment.”

https://pubmed.ncbi.nlm.nih.gov/36793188/

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202200698