A novel antioxidant and anti-inflammatory carboxymethylcellulose/chitosan hydrogel loaded with cannabidiol promotes the healing of radiation-combined wound skin injury in the 60Co γ-irradiated mice

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“Background: Combined radiation and wound skin injury (RW) are frequently observed in patients undergoing tumor surgery plus radiotherapy, and but specific treatment is lacking. Chitosan (CS) and carboxymethyl cellulose (CMC) are commonly used to prepare hydrogel with good biocompatibility and low toxicity.

Cannabidiol (CBD) has presented anti-inflammatory, antioxidant, and neuroprotective properties.

Methods: CMC, CS, and CBD were used and designed for three types of hydrogels (CMC/CS2/CBD, CMC/CS3/CBD, CMC/CS4/CBD) with different ratios of CMC and CS based on previous report and our preliminary experiments. The CMC/CS/CBD hydrogel was synthesized using electrostatic interaction without chemical crosslinking, characterized via fourier transform infrared (FT-IR), and tested for mechanical properties, swelling behavior, biocompatibility, antioxidant activity, cytotoxicity, and hemocompatibility. 60Co γ irradiation (5 Gy, 0.62 Gy/min) combined with 1 cm circular trauma was applied to establish RW mice model. Topical applications of CMC/CS3, CMC/CS2/CBD, CMC/CS3/CBD were used to treat RW injury once a day for 10 consecutive days. The mice were euthanized 7, 14, 21 days after radiation, and samples were collected.

Results: FT-IR confirmed the successful formation of a polyelectrolyte network. The CMC/CS3/CBD hydrogel exhibited optimal mechanical strength, rapid gelation, high swelling capacity, and excellent biocompatibility. Both CMC/CS2/CBD and CMC/CS3/CBD hydrogels effectively improved RW injury 7, 14, 21 days after radiation. Reduced inflammation and increased collagen production were observed the two groups. The significant increased expression of interleukin (IL)-1β, IL-22, IL-17A, IL-6, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, CC motif chemokine ligand (CCL)2, CCL3, CCL4, CCL5, CCL11 in the RW group was greatly inhibited after treatment with CMC/CS3/CBD hydrogel. Transcriptome analysis revealed the hydrogel’s impact on lipid metabolism and epithelial differentiation pathways.

Conclusions: By integrating CBD into a CMC/CS-based hydrogel without using toxic crosslinkers, this study provides a novel, biomaterial-based, biocompatible approach for RW injury. These findings pave the way for future clinical application of CMC/CS3/CBD hydrogel in RW injury.”

https://pubmed.ncbi.nlm.nih.gov/40318533/

“We developed an injectable CMC/CS/CBD hydrogel for the treatment of RW injuries. The hydrogel was fabricated via electrostatic self-assembly, eliminating the need for toxic chemical crosslinkers, exhibiting excellent biocompatibility and low cytotoxicity. Our work firstly integrated CBD into a hydrogel matrix specifically for RW treatment, and confirmed its ability to suppress inflammation and regulate macrophage polarization.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711325004283?via%3Dihub

Efficacy of a Neuroimmune Therapy Including Pineal Methoxyindoles, Angiotensin 1-7, and Endocannabinoids in Cancer, Autoimmune, and Neurodegenerative Diseases

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“Purpose: Recent advancements in psycho-neuro-endocrine-immunology indicate that numerous noncommunicable diseases (NCDs) originate from disruptions in the cytokine immune network, resulting in chronic inflammatory responses. This persistent low-degree inflammation is attributed to deficiencies in crucial endogenous anti-inflammatory neuroendocrine systems, including the pineal gland, the endocannabinoid system, and the angiotensin-converting enzyme 2 / angiotensin 1-7 axis.

The administration of pineal methoxyindoles (melatonin, 5-methoxytryptamine), cannabinoids, and angiotensin 1-7 may entail potential therapeutic benefits for NCDs, particularly for patients who do not respond to conventional treatments.

Patients and methods: This study evaluates the safety and efficacy of a neuroimmune regimen comprising melatonin (100 mg/day at night), 5-methoxytryptamine (30 mg in the early afternoon), angiotensin 1-7 (0.5 mg twice daily), and cannabidiol (20 mg twice daily) in 306 patients with NCDs, including advanced cancer, autoimmune diseases, neurodegenerative disorders, depression, and cardiovascular disease.

Results: The neuroimmune regimen successfully halted cancer progression in 68% of cancer patients, who also reported improvements in mood, sleep, and relief from anxiety, pain, and fatigue. In patients with autoimmune diseases, the treatment effectively controlled the disease process, remarkable in cases of multiple sclerosis. Additionally, positive outcomes were observed in patients with Parkinson’s disease, Alzheimer’s disease, and depression.

Conclusion: Randomized controlled trials are required to assess this therapeutic approach for NCDs that includes endogenous neuroendocrine molecules regulating immune responses in an anti-inflammatory manner.”

https://pubmed.ncbi.nlm.nih.gov/40330271/

“This study highlights the potential of leveraging endogenous molecules to treat NCDs by modulating cell proliferation, inflammation, immune responses, metabolism, and neurological functions. The findings suggest that a neuroimmune regimen incorporating melatonin, angiotensin 1–7, and other bioactive compounds could offer a low-cost, minimally toxic therapeutic approach.”

https://www.dovepress.com/efficacy-of-a-neuroimmune-therapy-including-pineal-methoxyindoles-angi-peer-reviewed-fulltext-article-CIA

Effects of heat reflux extraction on the content, antioxidant, and immune activity of polyphenols and flavonoids from hempseed threshing residues

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“Objective: Hempseed threshing residues are rich in phytochemicals such as polyphenols and flavonoids. Phenolic and flavonoid compounds have been associated with antioxidant, antibacterial and anticancer activities. The re-use of the hempseed threshing residues as value-added materials is, not only cost-saving, but also environmentally beneficial. It is therefore important to develop an effective method for extraction of phenolic compounds and flavonoids from hempseed threshing residues.

Methods: In this investigation, the extraction of phenolic constituents and flavonoids from hempseed threshing residues using heat reflux extraction (HRE) were optimized through response surface methodology (RSM). Four HRE parameters to enhance the yield of crude extracts (CE), total phenolic content (TPC), and total flavonoids content (TFC) were evaluated. Additionally, the study evaluated the chemical compounds, antioxidant characteristics of the extracts, and the immune activity of the extracts was assessed by quantifying the levels of inflammatory cytokines, specifically IL-6, IL-10, and TNF-α.

Results: The best extraction parameters were determined as: for the extraction time of 69.71 min, a liquid-solid proportion of 5.12:1, a particle size of 1150 µm, and an ethanol concentration of 69.60%. Under these optimized conditions, the yields for CE, TPC, and TFC were 4.74%, 27.54%, and 16.02% respectively. The data conformed well to multiple regression models, showing that these extraction parameters markedly influence the yields of CE, TPC, and TFC. Most of the compounds found may belong to the class of polyphenol and flavonoids. Cellular assays indicated that extracts from hempseed threshing residue notably reduced pro-inflammatory factors (TNF-α, IL-6) and increased anti-inflammatory factors (IL-10) in RAW 264.7 cells.

Conclusion: This research lays a theoretical foundation for extracting polyphenols and flavonoids from hempseed threshing residue and for the comprehensive assessment of antioxidant and immune-enhancing products. However, the antioxidant and immune activity of hempseed threshing residues extracts under physiological conditions in vivo, and the relevant mechanism should be further studied.”

https://pubmed.ncbi.nlm.nih.gov/40333885/

“These findings highlight the potential of utilizing hempseed threshing residues in food or health product industries as natural alternatives to synthetic antioxidants.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0322134

Cannabinoids: Therapeutic Perspectives for Management of Orofacial Pain, Oral Inflammation and Bone Healing-A Systematic Review

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“Cannabinoids, particularly cannabidiol (CBD) and tetrahydrocannabinol (THC), have been increasingly studied for their therapeutic applications in various medical fields. This systematic review aims to explore their role in oral surgery, focusing on pain management, inflammation control, and bone regeneration.

A systematic review was conducted using the PRISMA framework to identify relevant studies from the PubMed, Scopus, and Web of Science databases published up to November 2024. The review included clinical and preclinical studies investigating the effects of cannabinoids on orofacial pain, oral inflammation, and bone healing. Data on study design, cannabinoid types, and relevant outcomes were extracted and analyzed. CBD was the most commonly studied compound, with other studies evaluating CB1/CB2 receptor agonists, THC, and cannabis smoke.

Clinical trials showed mixed results: some studies found CBD effective in reducing dental or myofascial pain, while others found limited or non-superior outcomes compared to standard treatments (e.g., NSAIDs, corticosteroids). Among the four RCTs, three had a low risk of bias, and one moderate; all nine animal studies had a high risk of bias.

In conclusion, preclinical and clinical studies suggest that cannabinoids represent a promising non-opioid alternative for pain management and for oral inflammation.

Although some evidence suggests potential benefits of cannabinoids, particularly CBD, in oral health contexts, findings are derived from heterogeneous studies-many with high risk of bias. More high-quality, standardized clinical trials are necessary before recommending cannabinoids for routine dental practice.”

https://pubmed.ncbi.nlm.nih.gov/40332414/

“Within the limitations of this review, cannabinoids—especially cannabidiol (CBD)—demonstrated potential in managing orofacial pain, reducing inflammation, and promoting bone healing.”

https://www.mdpi.com/1422-0067/26/8/3766

Cannabinoids: Adaptogens or Not?

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“Since ancient times, humanity has been exploring natural substances with the aim of increasing stress resistance, enhancing biochemical homeostasis, and treating different diseases. In this way, the objective of the present review is to compare the biological effects of cannabinoids (CNBs) with adaptogens, this exploration allows us to consider the controversy if they can be classified together considering the effects on the body.

First, the work revises different features of adaptogens such as their chemical structure, ligand-receptors properties, and homeostasis-stress capabilities. Also, this review includes an overview of preclinical and clinical studies of the effect of adaptogens considering a broad spectrum of adverse biological, chemical, and physical factors.

Then, the work does a review of the CNBs effects on the body including the principal uses for the treatment of several diseases as neurodegenerative disorders, arthritis, cancer, cardiovascular affections, diabetes, anxiety, chronic pain, among others. In addition, the different characteristics of the specific endocannabinoid system are described explaining the wide CNBs body effects.

Finally, this review presents a comparative analysis between CNBs and adaptogens properties, expecting to contribute to understanding if CNBs can be classified as adaptogens.”

https://pubmed.ncbi.nlm.nih.gov/40332769/

https://www.liebertpub.com/doi/10.1089/can.2024.0108

“Adaptogens are herbs and plant-based substances believed to help the body manage stress and restore balance after stressful situations”

“Adaptogens are active ingredients in certain plants and mushrooms that may impact how your body deals with stress, anxiety and fatigue.”

Impact of cannabis consumption on perioperative outcomes in patients undergoing hepatobiliary and pancreatic surgery: a nationwide analysis

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“Background: There is paucity of high-quality data on the effect of cannabis consumption on perioperative outcomes after hepatobiliary and pancreatic (HPB) surgery.

Methods: Data from the Nationwide Inpatient Sample (2016-2020) were used. In-hospital complications, length-of-stay and hospitalisation charges were compared among patients undergoing HPB surgery.

Results: We identified 191,315 patients, of which 1705 (0.89 %) were cannabis consumers. Cannabis consumers were more likely to be male (67.5 % vs 50.2 %), younger, and Black (22.6 % vs 11.0); p < 0.001 for all. Multivariate analysis demonstrated a significantly lower risk of pneumonia (OR 0.54, 95 % CI 0.29-0.99) among cannabis consumers. There was no significant difference in risk of in-hospital mortality (OR 0.64, 95 % CI 0.31-1.30), acute kidney injury, hemodialysis, blood transfusion, vasopressor use, invasive and non-invasive mechanical ventilation, venous thromboembolism, portal vein thrombosis, intraabdominal abscess, peritonitis, surgical site infection, post-procedure haemorrhage/hematoma, wound dehiscence, liver failure, or sudden cardiac arrest. There was no significant difference in length-of-stay (mean 10.99 vs 9.69 days; p = 0.348) or hospitalisation costs ($49,444 vs $43,661; p = 0.109).

Conclusion: There is no significant difference in major perioperative complications after HPB surgery among patients with cannabis use disorder. Further, there is no significant difference in health services utilisation among consumers versus non-consumers.”

https://pubmed.ncbi.nlm.nih.gov/40324909/

https://www.hpbonline.org/article/S1365-182X(25)00550-7/abstract

Cannabigerol and Cannabinoid Receptors in Major Depressive Disorder: Network Pharmacology, Molecular Docking, and In-vivo Analysis

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“Introduction: Cannabigerol (CBG), being one of the non-psychotropic phyto-cannabinoid, has been labelled and recognized to be antioxidant and neuroprotective; it may conceivably hold depression-relieving activity. Consequently, the objective of the present research procedure was to explore the depression-alleviating competence of cannabigerol in both stressed and unstressed mice using computational/in-silico modelling, followed by in-vivo analysis.

Method: Target genes for Major Depressive Disorder (MDD) were identified using GeneCards and Swiss Target Prediction, with common targets screened via Venny software. STRING database anal-ysis established protein-protein interactions (PPI), identifying CNR2 (CB2 receptor) as a key target. Molecular docking of CBG with CB2 (PDB ID: 8GUR) showed strong binding, prompting in vivo evaluation. ADME profiling via Schrödinger Maestro v10.5 confirmed CBG’s high oral absorption and favorable pharmacokinetics. Male Swiss albino mice underwent chronic unpredictable mild stress (CUMS) for three successive weeks, with CBG (10, 20, 40 mg/kg) and imipramine (15 mg/kg) administered and various behavioral and biochemical parameters being analyzed.

Results: Cannabigerol demonstrated maximum oral absorption in ADME predictions using Schrö-dinger’s Maestro (v10.5). Wayne diagram illustrated MDD-related targets, with CB2 (CNR2) rank-ings in top targets, based on SwissADME and Venny software analysis. Docking analysis revealed a high binding affinity (-10.53) for CB2, outperforming cannabidiol (-9.56) and comparable to Δ9-THC (-10.11). During in vivo evaluation, CBG (40 mg/kg) and Imipramine 15mg/kg significantly reduced CUMS-induced exalted plasma corticosterone, nitrite quantities, and monoamine oxidase-A action in the brain of stressed mice. Additionally, both treatments substantially reversed the unpre-dictable chronic stress-induced decline in catalase action, demonstrating CBG’s possible potential in alleviating depression-like symptoms in mice.

Conclusion: Cannabigerol has shown significant depressive alleviating potential in mice exposed to chronic and unpredictable stress regimes, possibly via interaction with cannabinoid receptors as in-dicated by in-silico modelling, which has been validated by our findings of the in-vivo protocol.”

https://pubmed.ncbi.nlm.nih.gov/40326034/

https://www.eurekaselect.com/article/148152

Genotoxic assessment of a Cannabis sativa L. extract

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“Context: As a naturally occurring terpenoid found in Cannabis sativa L. (Cannabaceae), cannabidiol (CBD) has gained public and industry interest for the purposes of personal well-being as a foodstuff and pharmaceutical. Despite a number of publications on CBD toxicology, many have significant limitations, especially those relating to genotoxicity. These include poor characterization of the CBD extract and/or lack rigor in conforming to accepted regulatory guidelines and best practice. A number of regulatory agencies have highlighted these issues and requested additional genotoxicity data to help ensure the safe use of CBD.

Objective: To provide insights into the genotoxicity of a CBD isolate and its lipid carrier.

Materials and methods: We have conducted an in vitro mammalian cell micronucleus (OECD 487) and a bacterial reverse mutagenicity assay (Ames test) (OECD 471) in a CBD isolate (97% > CBD) with its carrier.

Results: The samples tested were non-mutagenic, as determined in the Ames test. The in vitro micronucleus assay conducted was negative for genotoxicity, with no statistically significant increases in the incidences of micronucleated cells observed at any dose compared to negative controls.

Conclusions: These studies confirm that this CBD rich isolate in combination with its carrier, are unlikely to post any genotoxic hazard at exposure levels expected in foods.”

https://pubmed.ncbi.nlm.nih.gov/40326262/

“In summary, the potential genotoxicity of the CBD test substance was assessed using a mammalian cell micronucleus test and Ames test. These tests respectively assess chromosomal damage and base changes, or frameshift mutations in the genome. Application of these assays to the CBD test substance did not produce any evidence of genotoxic effects, findings that are consistent with other studies.”

https://www.tandfonline.com/doi/full/10.1080/13880209.2025.2499075

Cannabis use is associated with less peripheral inflammation but similar insulin sensitivity as non-use in healthy adults

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“Objective: This study tested whether cannabis affects inflammation and insulin sensitivity and if this varied based on THC:CBD ratios. Participants who currently used cannabis were assigned to use one of three cannabis flower products ad libitum for four weeks and compared to non-using participants.

Methods: Healthy participants 21 to 40 years old without diabetes were included. Participants had to engage in ≥ weekly cannabis use for ≥ one year (cannabis use groups) or no cannabis use in the past year (cannabis non-use group). Participants who used cannabis purchased and used a THC-dominant (23% THC, 0% CBD), THC+CBD (10% THC, 8% CBD), or CBD-dominant product (20% CBD, 1% THC). Peripheral inflammation was assessed with several cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-12, IFNG, IL10) and one chemokine (MCP-1). Insulin sensitivity was assessed via the Matsuda Index.

Results: Models were intent-to-treat and utilized maximum likelihood estimation. Cannabis use was associated with lower peripheral inflammation (p<.001) than non-use. THC:CBD ratio of products used over four weeks did not change peripheral inflammation levels nor affect insulin sensitivity compared to non-use.

Conclusions: Habitual cannabis use (vs. non-use) is associated with lower peripheral inflammation with no difference in insulin sensitivity in metabolically healthy, young people.”

https://pubmed.ncbi.nlm.nih.gov/40324550/

https://www.amjmed.com/article/S0002-9343(25)00281-5/abstract

Cannabis use is associated with a lower likelihood of presence of HIV drug resistance mutations in a retrospective cohort of adults with HIV

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“Objectives: A significant clinical concern in the era of Pre-Exposure Prophylaxis (PrEP) is the increased incidence of HIV Anti-Retroviral Drug Resistance Mutations (ARV-DRM). Previous research has indicated that there is an association between substance use and failed viral suppression, which can lead to ARV-DRM. The goal of this retrospective study was to investigate whether substance use as determined by at least one positive urinalysis screen is associated with increased/decreased odds of having a ARV-DRM.

Methods: This study used firth logistic regression analyses of data retrieved from the National NeuroAIDS Tissue Consortium Data Coordinating Center to examine the relationship between substance use and ARV-DRM. The dataset analyzed 614 participants with the following criteria: HIV+ status, at least one paired plasma and cerebrospinal fluid (CSF) viral load measurement, at least one urinalysis of substance use, at least 18 years of age, and analysis of DRM in CSF/Plasma.

Results: Cannabis use was a significant predictor of ARV-DRM and was associated with a lower odds of having ARV-DRM (odds ratio=0.189), after accounting for demographic variables and the interaction between polysubstance use and cannabis use. A significant negative relationship was observed between a cannabis positive test and high viremia (>1,000 copies/mL) but not between a cannabis positive test and CSF Escape (viral load CSF>viral load plasma).

Conclusions: The above results may suggest an immunomodulatory role for cannabis that impacts the propensity for ARV-DRM. These findings could incentivize future research to further investigate effects of cannabis use on the development of HIV ARV-DRM.”

https://pubmed.ncbi.nlm.nih.gov/40313366/

“We have found that cannabis use is significantly associated with a decreased likelihood of HIV ARV-DRM and suggest that cannabis use may be a protective factor against the development of anti-retroviral drug resistance mutations. “

https://www.degruyterbrill.com/document/doi/10.1515/nipt-2024-0010/html