Monthly Archives: July 2025

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 Nrf2, Bax, Bcl-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

Ageing, Neurodegeneration and the Endocannabinoid System

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“Numerous studies carried out in the last 30-40 years have strongly demonstrated that the endocannabinoid system exerts important modulatory functions in the central nervous system (CNS). These neuromodulatory functions encompass the whole life of animals, with specific activities during neurodevelopment (prenatal, postnatal and adolescent periods), adulthood and possibly senescence too. However, this is the life stage less investigated in relation with the endocannabinoid system to date.

In the aged brain, the activity of this system appears to be altered, which contributes to subtle impairments that typically occur during ageing in learning and memory, motor behaviour, social behaviour and other neurobiological functions. Some of the changes in endocannabinoid activity may represent a process to attenuate ageing-related impairment in the brain function, which is consistent with its role as a pro-homeostatic system.

An important observation is that these alterations become extreme when normal brain ageing acquires pathological characteristics, as happens in chronic neurodegenerative disorders. This includes the cannabinoid type-1 (CB1) receptor downregulation or impairment in its signalling and the increase in endocannabinoid-inactivating enzymes, both hypothesised to contribute to pathogenic events. By contrast, elevated levels of endocannabinoids due to a reduced Fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) expression and the upregulation of cannabinoid type-2 (CB2) receptors may in turn serve as endogenous pro-homeostatic adaptations against brain impairment.

This review synthesises information on: (i) subtle alterations in the endocannabinoid system in the senescent brain in the absence of pathology, with the purpose of demonstrating that these alterations are representative of the extreme changes experienced by this system in the brain pathological ageing; and (ii) the development of neuroprotective therapies based on the pharmacological management of specific endocannabinoid targets to combat neurodegenerative pathologies.

Together, research in this area comes at a critical time as global lifespan is increasing, incidence of age-related neurodegenerative disorders is expanding, and the unmet need for efficacious neuroprotective treatments is a public health necessity.”

https://pubmed.ncbi.nlm.nih.gov/40707697/

https://link.springer.com/chapter/10.1007/7854_2025_597

Cannabinoid Derived Product is a Potential Novel Therapeutic for Papillary Thyroid Carcinoma

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“Rationale: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer that typically affects women ages 20 to 50, presenting as an asymptomatic neck mass. Treatment with total or partial thyroidectomy shows an excellent prognosis. However, investigation of non-invasive therapeutic options with minimal adverse effects is ongoing. This study seeks to investigate the K1 cell line, which consists of PTC cells obtained from metastatic tumors of well-differentiated PTC.

Objective: Our investigation focuses on a cannabinoid-based product (named BRF1-A) and its potential anti-cancer effects through modulation of gene expression. We investigated its effects on gene expression of p53, c-Myc, and BCL-2 in K1 papillary thyroid cancer cells.

Methods: BRF1A was co-cultured with K1 cell line (1 × 106 cells/ml) and incubated at 37°C under 5% CO2 for 24 and 48 hours. After the culture time points, the cells were harvested, and cell viability was determined via trypan blue exclusion assay. Using qRT-PCR, we determined the effect on the gene expression of TP53, c-Myc, and BCL-2.

Results: Results show that the BRF1A decreased the viability of K1 PTC cells in a dose and time-dependent manner. Within 24 hours, the cannabinoid- containing product increased the gene expression of TP53 and decreased the gene expression of BCL-2 and c-Myc in K1 PTC cells.

Conclusion: The results suggest that the cannabinoid-containing product BRF1A interacts as a potential regulator in well-differentiated thyroid cancer with the upregulation of p53 and downregulation of BLC-2 and c-Myc. Further in vitro and in vivo studies are needed to understand the exact mechanism and therapeutic potential of the cannabinoid-containing products in papillary thyroid cancer.”

https://pubmed.ncbi.nlm.nih.gov/40703048/

“Our results suggest that a cannabinoid-containing product, BRF1A, functions as a potential regulator of thyroid cancer cells by upregulating tumor suppressor p53 and downregulating c-Myc and BCL-2. BRF1A may have potential therapeutic benefits in the treatment of thyroid carcinoma and warrants further investigation in vitro and in vivo of its potential mechanism.”

https://journals.sagepub.com/doi/10.1177/15347354251332966

Cannabis-derived cellulose acetate electrospun membranes for therapeutic dressings: extraction, characterization, and prototype development

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“This work reports the development of electrospun cellulose acetate (CA) membranes derived from Cannabis sativa biomass for potential use in therapeutic dressings.

Cellulose was extracted from cannabis stalks using alkaline pulping and bleaching, followed by homogeneous acetylation to obtain CA with controlled substitution. CA solutions (13%-25%) were electrospun under varying parameters, and the 17% formulation yielded the most homogeneous, bead-free nanofibers. The resulting membranes were characterized using FTIR, XRD, Raman spectroscopy, UV-Vis spectrophotometry, and SEM. FTIR and Raman confirmed acetylation through characteristic ester and methyl group vibrations.

XRD revealed reduced crystallinity in CA compared to native cellulose. SEM analysis showed uniform fiber networks with diameters between 500 and 800 nm. A bilayer dressing prototype was fabricated by integrating the electrospun membrane with a medical-grade silicone adhesive. Adhesion performance was evaluated on synthetic skin using a FINAT-standardized 180° peel test.

The membranes demonstrated adequate mechanical cohesion and conformability, supporting their application as sustainable, plant-based biomedical patches.”

https://pubmed.ncbi.nlm.nih.gov/40698058/

“Taken together, this work presents the first full validation of cannabis-derived cellulose acetate as a processable, biocompatible, and functionally versatile material for advanced medical dressing systems.

Collectively, these findings support the use of Cannabis sativa as a viable and sustainable raw material for the development of high-performance cellulose acetate membranes. The study demonstrates not only the chemical and morphological comparability of cannabis-derived materials to commercial analogs but also their potential in next-generation biomedical and filtration technologies.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2025.1624736/full

Medical Cannabis Use and Healthcare Utilization Among Patients with Chronic Pain: A Causal Inference Analysis Using TMLE

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“Introduction: Chronic pain affects approximately 20% of U.S. adults, imposing significant burdens on individuals and healthcare systems. Medical cannabis has emerged as a potential therapy, yet its impact on healthcare utilization remains unclear.

Methods: This retrospective cohort study analyzed administrative data from a telehealth platform providing medical cannabis certifications across 36 U.S. states. Patients were classified as cannabis-exposed if they had used cannabis in the past year, while unexposed patients had no prior cannabis use. Outcomes included self-reported urgent care visits, emergency department (ED) visits, hospitalizations, and quality of life (QoL), measured using the CDC’s Healthy Days measure. Targeted Maximum Likelihood Estimation with SuperLearner estimated causal effects, adjusting for numerous covariates.

Results: Medical cannabis users exhibited significantly lower healthcare utilization. Specifically, exposure was associated with a 2.0 percentage point reduction in urgent care visits (95% CI: -0.036, -0.004), a 3.2 percentage point reduction in ED visits (95% CI: -0.051, -0.012) and fewer unhealthy days per month (-3.52 days, 95% CI: -4.28, -2.76). Hospitalization rates trended lower but were not statistically significant. Covariate balance and propensity score overlap indicated well-fitting models.

Conclusions: Medical cannabis use was associated with reduced healthcare utilization and improved self-reported QoL among chronic pain patients.”

https://pubmed.ncbi.nlm.nih.gov/40700267/

“The findings of this study suggest, in line with existing research, that medical cannabis is likely an effective treatment option for patients with chronic pain. Moreover, we found that, in addition to an increase in QoL, medical cannabis exposure is associated with lower risk of urgent care and ED visits, when comparing patients who used medical cannabis for at least one year to cannabis-naïve patients. This underscores the potential for not only QoL gains associated with medical cannabis use, but also positive downstream effects on the healthcare system resulting from treatment.”

https://www.mdpi.com/2226-4787/13/4/96