Targeting Vascular and Inflammatory Crosstalk: Cannabigerol as a Dual-Pathway Modulator in Rosacea

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“Rosacea is a chronic inflammatory skin condition characterized by persistent erythema and abnormal vascular response. Although current treatments focus on symptomatic relief, they often provide only temporary improvement and may be associated with side effects or recurrence.

Cannabigerol (CBG), a non-psychoactive cannabinoid, has recently garnered attention for its pharmacological activities, including anti-inflammatory, antioxidant, neuroprotective, and skin barrier-supportive effects. However, its role in modulating pathological responses in rosacea remains unclear.

In this study, we investigated the therapeutic potential of topically applied CBG in an LL-37-induced rosacea-like mouse model.

Clinical and histological assessments revealed that CBG markedly reduced erythema, epidermal hyperplasia, and mast cell infiltration. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed downregulation of Il1bIl4Il6Il13Il22Il31Tlr2Vegfa, and Mmp9. Immunohistochemistry and Western blot analyses further demonstrated suppression of CD31, vascular endothelial growth factor (VEGF), and Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), along with reduced activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, including decreased levels of JAK1, STAT3, and phosphorylated STAT3.

These findings suggest that topical CBG alleviates rosacea-like skin inflammation by targeting inflammatory and vascular pathways, including JAK/STAT and YAP/TAZ signaling.”

https://pubmed.ncbi.nlm.nih.gov/40725084/

“In conclusion, our study demonstrated the therapeutic potential of CBG in an LL-37-induced mouse model of rosacea. Topical CBG treatment significantly reduced clinical erythema, epidermal hyperplasia, and mast cell infiltration, and suppressed key inflammatory and vascular mediators at both the mRNA and protein levels. Mechanistically, CBG inhibited the expression of cytokines, Vegfa, and Tlr2, as well as the activation of YAP/TAZ and JAK/STAT signaling pathways, which are known to be involved in rosacea pathogenesis.

These findings highlight CBG as a promising non-psychoactive cannabinoid with therapeutic relevance for the treatment of rosacea.”

https://www.mdpi.com/1422-0067/26/14/6840

Trans-Cannabitriol as a Dual Inhibition of MPOX Adhesion Receptors L1R and E8L: An In Silico Perspective

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“The re-emergence of monkeypox virus (MPXV) as a global public health concern highlights the urgent need for novel therapeutic strategies targeting viral proteins essential for infection.

This study investigates the inhibitory potential of Trans-Cannabitriol (trans-CBT), a minor cannabinoid, against MPXV proteins L1R, H3L, and E8L using an integrative in silico framework.

Homology modeling was employed to generate 3D structures of these proteins, followed by molecular docking and 1 µs molecular dynamics (MD) simulations. The trans-CBT demonstrated strong binding affinities for L1R (-10.76 kcal/mol) and E8L (-8.531 kcal/mol), with weaker interactions observed for H3L (-5.739 kcal/mol).

Four MD simulations of 1 µs revealed that trans-CBT stabilizes L1R by reducing its flexibility and solvent exposure, potentially inhibiting viral entry into host cells. In contrast, trans-CBT increased the flexibility and conformational changes of E8L, possibly impairing its function in viral attachment and pathogenesis. ADMET and target prediction analyses further supported its drug-likeness and safety, with the absence of strong CB1/CB2 binding suggesting that trans-CBT may exert its antiviral effects independently of classical cannabinoid pathways.

These findings provide insights into the diverse mechanisms of action of trans-CBT on MPXV proteins and underscore its potential as a broad-spectrum antiviral agent. While promising, further experimental validation and optimization are necessary to assess the real-world applicability of trans-CBT in combating MPXV infections.

This work contributes to the expanding field of cannabinoid-derived antivirals and highlights the importance of exploring under-investigated phytochemicals for therapeutic applications.”

https://pubmed.ncbi.nlm.nih.gov/40718062/

“The trans-CBT shows promise as an antiviral agent targeting MPXV proteins L1R and E8L. Molecular docking identified trans-CBT as the best-binding ligand for these proteins, with MD simulations revealing distinct effects: it stabilizes L1R by reducing flexibility and solvent exposure, potentially inhibiting viral entry, while it increases E8L’s flexibility and disrupts its conformation, possibly impairing its function.”

https://journals.sagepub.com/doi/10.1177/11779322251355315

Dietary Hemp (Cannabis sativa L.) Products Enhance Egg Yolk Omega-3 Fatty Acids and Color Without Compromising Laying-Hen Performance: A Meta-Analysis

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“Hemp (Cannabis sativa L.) products have gained attention in poultry nutrition for their rich content of polyunsaturated fatty acids (PUFAs), bioactive compounds, and potential functional benefits. However, findings on their impact on laying-hen performance, egg quality, and yolk fatty acid profiles have been inconsistent.

This meta-analysis aimed to evaluate the effects of dietary hemp products on laying-hen performance, egg quality traits, and yolk fatty acid composition, while exploring potential sources of heterogeneity across studies.

A comprehensive literature search identified 21 studies that met the inclusion criteria. A random-effects model was used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CIs) for various outcomes, including production performance, egg quality, and yolk fatty acid profiles. Subgroup and meta-regression analyses assessed the influence of factors such as inclusion level, hen age, and hemp product type.

The results showed that hemp supplementation had no significant effect on hen-day production, egg mass, feed conversion ratio, or feed intake. However, yolk redness (SMD = 4.40; 95% CI: 2.46, 6.33; p < 0.001) and yellowness (SMD = 4.45; 95% CI: 2.75, 6.16; p < 0.001) were significantly enhanced. Hemp feeding also increased n-3 PUFA levels in egg yolk, including C18:3n3, C20:5n3, and C22:6n3, while reducing saturated and monounsaturated fatty acids. Subgroup analysis indicated that inclusion levels > 10% and hen age ≤ 25 weeks were associated with slight reductions in hen-day production, whereas older hens (>25 weeks) showed increased egg weight.

In conclusion, hemp products can enrich yolk pigmentation and n-3 PUFA content in eggs, supporting the production of functional, value-added eggs without compromising the laying-hen performance.”

https://pubmed.ncbi.nlm.nih.gov/40723525/

“This meta-analysis underscores the potential of hemp-derived products as functional feed ingredients in laying-hen nutrition. Supplementation with hempseed, hempseed cake, or hempseed oil was found to significantly enhance yolk pigmentation and enrich long-chain omega-3 fatty acids, particularly DHA, without adversely affecting key performance metrics such as hen-day egg production, egg mass, or feed conversion ratio when inclusion levels are appropriately managed. Subgroup analyses revealed that inclusion levels above 10% and use in younger hens (≤25 weeks) may negatively impact productivity, whereas older hens exhibited improved egg weight. Among the different hemp product types, hemp oil demonstrated the most pronounced benefits for yolk coloration and fatty acid enrichment.”

https://www.mdpi.com/2076-2615/15/14/2062

Cannabis Use for Chronic Pain in Sickle Cell Disease: A Scoping Review

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“Purpose: The purposes of this scoping review were to: (1) systematically evaluate the literature on the types and effectiveness of cannabis and cannabinoids for pain management in adults with sickle cell disease (SCD), (2) assess the effect of cannabis and cannabinoids on pain outcomes, and (3) identify research gaps.

Design: Systematic scoping review.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, relevant studies were identified across PubMed, CINAHL, and Cannakeys databases. Inclusion criteria were studies involving medical and recreational cannabis use in adult SCD patients addressing pain management. Exclusion criteria included studies on pediatric populations, non-English publications, or case reports.

Results: Of 369 articles, 12 met inclusion criteria (one clinical trial, two reviews, seven observational, one mixed-methods, and one qualitative study), revealing mixed but generally positive evidence on cannabinoid effectiveness. While some studies indicated reduced pain scores with inhaled cannabis, results varied for other pain outcomes, such as hospitalizations for vaso-occlusive crises, and raised safety concerns, particularly with synthetic cannabinoids.

Conclusions: Cannabinoids may help manage SCD pain, though evidence remains mixed. No studies showed exacerbation of SCD symptoms, but safety concerns warrant careful use.

Clinical implications: The variability in outcomes underscores the need for personalized cannabis-based treatment plans and further research on standardized dosing and long-term safety.”

https://pubmed.ncbi.nlm.nih.gov/40713408/

https://www.painmanagementnursing.org/article/S1524-9042(25)00201-2/abstract

Dietary cannabidiol oil mitigates metabolic dysfunction in mice with high-fat diet-induced obesity

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“Metabolic syndrome (MetS) is a widespread health concern driven largely by lifestyle behaviors such as dietary choices and physical inactivity. Excessive caloric intake promotes adiposity and dysregulation of metabolic signaling in adipose tissue.

This study employed a mouse model of diet-induced obesity to evaluate the ability of cannabidiol (CBD), a cannabis-derived phytochemical, to mitigate metabolic dysfunction. Five-week-old mice received a standard diet or a high-fat diet (HF) with or without CBD (25 mg/kg bw) for 9 weeks.

CBD supplementation reduced weight gain and lowered serum glucose concentration in HF mice. These improvements were accompanied by reduced white adipose tissue mass and smaller adipocyte size. Additionally, CBD treatment recovered protein levels of key metabolic regulators, including peroxisome proliferator-activated receptor-γ coactivator 1 alpha and Sirtuin 1, in both inguinal and epididymal adipose tissues.

Consistently, CBD supplementation upregulated the mRNA expression of Prdm16 and promoted uncoupling protein 1 at both mRNA and protein levels, showing the browning of adipose tissues. Upstream, CBD supplementation increased transient receptor potential vanilloid 1 (TRPV1) in HF mice at both the mRNA and protein levels, which possibly helped orchestrate the observed improvements.

In summary, dietary CBD mitigates weight gain and improves the metabolic health of HF-challenged mice, potentially through the promotion of white adipose tissue browning.”

https://pubmed.ncbi.nlm.nih.gov/40712842/

“Dietary cannabidiol mitigates body and adipose weight gain in obesity mice.”

https://www.sciencedirect.com/science/article/pii/S0955286325002037?via%3Dihub

Cannabidiol Extracted from Cannabis sativa L. Plant Shows Neuroprotective Impacts Against 6-HODA-Induced Neurotoxicity via Nrf2 Signal Transduction Pathway

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“Background: As a prevalent neurodegenerative illness, Parkinson’s disease (PD) is associated with serious disability and reduced quality of patients’ lives. Therefore, finding new adjuvant treatment approaches that can improve patients’ quality of life is crucial.

Objectives: This study evaluated the impacts of cannabidiol (CBD) on the PC12 cell line and elucidated its mechanism of action, emphasizing the antioxidant pathway.

Methods: First, CBD was extracted from the hemp plant. Then, the cells were treated with CBD at different dosages. After treatment, the cells were exposed to 6-HODA, and cell viability and apoptosis, reactive oxygen species (ROS) content, total antioxidant capacity, lipid peroxidation, super oxide dismutase (SOD) and GSH levels, as well as the Nrf2BaxBcl-2, and Casp3 genes’ expressions were measured.

Results: Cannabidiol augmented the cell viability and decreased the apoptosis rates of 6-HODA-exposed PC12 cells. Also, pretreatment of PC12 cells with CBD was associated with decreases in ROS and malondialdehyde (MDA) contents, and an improvement in total antioxidant capacity and SOD and GSH activities were also seen. In addition, CBD overexpressed Nrf2 and Bcl-2 genes in 6-HODA-exposed PC12 cells and, on the other hand, prevented the upregulation of Bax and Casp3.

Conclusions: Overall, it was concluded that CBD has neuroprotective impacts against 6-HODA-induced neurotoxicity via the Nrf2 signal transduction pathway.”

https://pubmed.ncbi.nlm.nih.gov/40718446/

“In general, it was concluded that CBD has neuroprotective impacts against 6-OHDA-induced neurotoxicity due to its antioxidant properties that mediate via the Nrf2 signaling pathway.”

https://brieflands.com/articles/ijpr-160499

In silico exploration of pyrocannabinoid interactions with key protein targets

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“Cannabinoids, particularly those derived from cannabis, attract considerable attention in recent years for their therapeutic potential in treating various diseases and ailments.

In this study, we identify cannabinoid byproducts that result from the combustion of cannabidiol-henceforth referred to as pyrocannabinoids-and employ molecular docking simulations to investigate their interactions with key protein targets implicated in different physiological processes. Specifically, we focus on peroxisome proliferator-activated receptor gamma, p21-activated kinase 1, CB1, CB2, and GPR119 proteins, elucidating the binding modes and affinities of pyrocannabinoid byproducts to these receptors. This investigation is done in collaboration with Real Isolates LLC.

Our findings reveal diverse ligand-protein interactions, with some pyrocannabinoids displaying favorable binding energies and stable ligand-protein complexes. However, variations in binding affinities across different proteins underscore the complex pharmacological profiles of the pyrocannabinoids. Furthermore, the prediction of adsorption, distribution, metabolism, excretion and toxicity properties highlights both promising and concerning aspects of cannabinoid pharmacokinetics, emphasizing the need for thorough preclinical evaluation. Additionally, our investigation into potential metabolic sites using cytochrome P450 enzymes provides insights into cannabinoid metabolites.

Overall, our study contributes to the understanding of pyrocannabinoid pharmacology and informs the rational design of pyrocannabinoid-based therapeutics. Further experimental validation is warranted to translate these findings into clinically relevant applications.”

https://pubmed.ncbi.nlm.nih.gov/40718581/

https://link.springer.com/article/10.1007/s40203-025-00391-9

Cannabidiol (CBD) and Colorectal Tumorigenesis: Potential Dual Modulatory Roles via the Serotonergic Pathway

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“The 2018 Farm Bill legalized hemp-derived cannabidiol (CBD) products containing less than 0.3% tetrahydrocannabinol (THC) in the United States. This legislative shift catalyzed both public and scientific interest in CBD’s potential health benefits. However, the rapid expansion of the CBD market has considerably outpaced rigorous scientific research, leaving many health claims largely unsubstantiated.

While preclinical studies suggest that CBD may exert antitumorigenic effects in colorectal cancer (CRC) by modulating cell proliferation, apoptosis, and inflammation, clinical evidence supporting these effects remains limited.

This review critically examines the current evidence on the role of CBD in colorectal tumorigenesis, with particular attention to its molecular mechanisms and interactions with the serotonergic system-a signaling pathway implicated in the development of CRC and possessing potential dual anti- and pro-tumorigenic properties. By influencing the serotonergic system, CBD may confer both protective and potentially deleterious effects during CRC development.

This review underscores the need for further research to elucidate the complex mechanisms of CBD in colorectal tumorigenesis and to evaluate its therapeutic potential in clinical settings. Understanding these interactions could pave the way for novel prevention and treatment strategies, optimizing the anticancer efficacy of CBD while mitigating unintended risks.”

https://pubmed.ncbi.nlm.nih.gov/40710186/

“Since hemp-derived cannabidiol products with less than 0.3% tetrahydrocannabinol became legal in 2018 in the United States, public interest in their health benefits has grown rapidly. However, scientific research has not kept pace, and many of the claimed benefits remain unproven.

Early preclinical studies suggest that cannabidiol may help to combat colorectal cancer by influencing how cancer cells grow and die. One of the possible mechanisms is through its interaction with the body’s serotonergic system—a pathway that can have both helpful and harmful effects on cancer development.

This review summarizes current scientific findings and emphasizes the need for more research to determine how cannabidiol works in the body and whether it is truly safe and effective for preventing or treating colorectal cancer. It offers important insights into the potentially dual effects of cannabidiol in the development of colorectal cancer amid its rapidly expanding use in health and wellness.”

https://www.mdpi.com/1718-7729/32/7/375

High CBD extract (CBD-X) modulates inflammation and immune cell activity in rheumatoid arthritis

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“Introduction: Rheumatoid arthritis (RA) is a debilitating autoimmune disease affecting approximately 1% of the global population and is associated with significant morbidity and mortality. Given the known anti-inflammatory effects of cannabinoids, we investigated the therapeutic potential of a high-CBD extract, termed CBD-X, by assessing its effects on immune cells and disease progression. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in RA.

Methods: We evaluated the effects of CBD-X on cells involved in RA pathogenesis using macrophages and primary human neutrophils as ex vivo models. In addition, two murine models of RA were applied: collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA).

Results: Ex vivo experiments demonstrated that CBD-X inhibited the secretion of pro-inflammatory cytokines, including IL-1β from macrophages and IL-8, IL-6, and TNF-α from human neutrophils, suggesting its potential to modulate inflammatory responses. Moreover, CBD-X attenuated NF-κB p65 and Akt phosphorylation downstream LPS-activation signal in neutrophils. To further evaluate its therapeutic effects, we employed two murine models of RA: collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA). In both models, CBD-X treatment resulted in a significant reduction of leukocyte levels in the blood, primarily through the suppression of neutrophil and monocyte populations, which play a central role in RA pathogenesis. Additionally, CBD-X reduced neutrophil migration to the joints in the CAIA model, highlighting its potential to alleviate joint inflammation. Furthermore, it modulated the neutrophil-to-macrophage ratio (NMR), an important marker of RA progression, an effect that was not observed with dexamethasone treatment, suggesting a distinct mechanism of immune regulation. Notably, CBD-X promoted the pro-resolving macrophages to the rheumatic joints. Importantly, CBD-X exerted its anti-inflammatory effect by downregulating TNF-α and MCP-1 while upregulating IL-10, a key anti-inflammatory cytokine involved in immune homeostasis.

Discussion: These findings indicate that CBD-X has a significant potential as a therapeutic agent for RA, offering a promising approach to modulate immune responses and reduce inflammation in RA patients.”

https://pubmed.ncbi.nlm.nih.gov/40709173/

“Cannabinoids, including CBD, have demonstrated anti-inflammatory effects in conditions like severe COVID-19 and may help prevent disease progression from mild to severe stages.”

“These results demonstrate that CBD-X treatment exerts an anti-inflammatory effect by reducing pro-inflammatory cytokines also enhances anti-inflammatory IL-10 levels highlighting its therapeutic potential in RA management.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1599109/full

Cannabinoid Receptor Modulation in Focal Ischemic Stroke: A Systematic Review and Meta-Analysis of Infarct Volume and Behavioral Deficits in Animal Models

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“Introduction: Stroke is a leading cause of morbidity and mortality worldwide, with ischemic stroke accounting for the majority of cases. The endocannabinoid system (ECS), comprising cannabinoid receptors CB1 and CB2, has been implicated in regulating physiological processes and has shown potential neuroprotective effects in preclinical studies. However, the precise impact of cannabinoid receptor modulation on stroke outcomes remains unclear. This systematic review and meta-analysis aimed to evaluate the impact of cannabinoid receptor modulation on infarct volume and behavioral deficits in animal models of focal ischemic stroke, with a primary focus on infarct outcomes.

Method: A comprehensive literature search was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, yielding 29 eligible studies for inclusion.

Results: The analysis revealed significant reductions in infarct volume with cannabinoid agonists, particularly CB1 and CB2 agonists, indicating their potential as neuroprotective agents. Subgroup analyses further highlighted specific agonists, such as ACEA and KN38-72717, as particularly effective in reducing infarct volume. Additionally, CB antagonists, particularly CB1 antagonists, such as SR141716, showed promising results in reducing infarct volume. Although improvements in neurological scores were observed with both agonists and antagonists, statistical significance was not reached, indicating the need for further investigation.

Conclusion: These results highlight the potential of cannabinoid receptor modulation as a neuroprotective strategy in ischemic strokes and underscore the need for further research to elucidate the underlying mechanisms and optimize therapeutic approaches.”

https://pubmed.ncbi.nlm.nih.gov/40706582/

https://karger.com/mpp/article/doi/10.1159/000547277/930925/Cannabinoid-Receptor-Modulation-in-Focal-Ischemic