Author Archives: David Worrell

Assessment of nutritional and functional profile of whole, hulled and germinated hemp (Cannabis sativa L.) seeds

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“Hemp seeds (Cannabis sativa L.) have received considerable attention due to their nutrient and phytochemical content. However, while the nutritional and functional profile of whole hemp seeds has been adequately described in the literature, these aspects have not been investigated for hulled seeds, especially germinated hemp seeds.

Therefore, the aim of this work was to explore the nutritional and functional profile of hulled seeds (DH) and germinated seeds (GH), compared to whole hemp seeds (WH), to elucidate their potential to be considered as viable alternatives for the food industry and animal feed.

The proximal composition, concentration of antinutritional compounds, amino acid profile (AA), fatty acid profile (FA), tocopherol and phenolic content, and antioxidant activity were determined. Protein quality was assessed after in vitro digestibility was determined, and lipid quality indices were calculated.

Compared to WH, hulled seeds had a higher content of crude protein (33.78% vs. 25.14%), crude fat (48.13% vs. 31.46%) and metabolizable energy (23.43 MJ kg-1 vs. 13.75 MJ kg-1), as well as the best in vitro protein digestibility (86.73% vs. 78.34%), which also ensured the best IVPDCAAS (in vitro protein digestibility corrected amino acid score) value.

Seed germination resulted in a significant increase in protein, fiber and minerals, as well as in the content of antioxidant compounds, responsible for the higher antioxidant activity compared to WH and DH.

In conclusion, hulling or germination improves the nutritional and functional profile of hemp seeds, confirming their potential for use in various emerging food matrices or in animal feed.”

https://pubmed.ncbi.nlm.nih.gov/42099769

“In the context of the growing interest in plant-based protein diets, our results suggest that hulled or germinated hemp seeds have the potential to serve as sustainable sources of protein and bioactive compounds (omega-3 and antioxidants).”

https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2026.1825902/full


Cannabinoids in autoimmune diseases: mechanistic insights and translational challenges

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“Cannabinoids are traditionally recognized for their effect on the nervous system. Emerging evidence suggests that cannabinoids mitigate inflammation driven by Th1/Th17 responses, which are linked to autoimmune diseases.

In addition to their symptomatic, and analgesic effects, cannabinoids suppress the immune response by modulating regulatory T-cell activity, reducing microglial activation, and help in maintaining the integrity of the epithelial barrier. These findings suggest that cannabinoids may be involved in immune, and metabolic regulatory pathways.

Despite the promising preclinical data, translating these findings into effective treatments for autoimmune disorders has proven challenging. Current human studies have primarily focused on symptomatic relief such as reducing spasticity, managing pain, improving sleep quality, and boosting appetite. However, few trials have included immune profiling, i.e., assessed cytokine panels, performed immune cell phenotyping, tracked relapses, or utilized inflammation-focused imaging endpoints. Consequently, documented benefits are primarily symptomatic, while potential disease-modifying effects are not yet adequately studied.

Cannabinoids interact with CB1, CB2, TRP, and PPAR-γ receptor proteins, suggesting that they may offer targeted immune modulation rather than broad immunosuppression, potentially overcoming limitations of conventional therapies.

Moreover, new compounds like cannabigerol (CBG), cannabidivarin (CBV), and CB2-selective agonists with minimal psychoactivity offer expanded therapeutic options. However, challenges persist due to variability in formulations, bioavailability issues, regulatory hurdles, and a lack of long-term safety data. Future clinical development will require standardised GMP-grade preparations, robust pharmacokinetic evaluation, and trials that include immune-related endpoints such as T-cell polarisation, inflammasome markers, oxidative stress profiles, microbiome signatures, and longitudinal imaging, to clarify their therapeutic potential in autoimmune diseases.”

https://pubmed.ncbi.nlm.nih.gov/42105814

“Cannabinoids are versatile bioactive compounds that modulate immune function, and inflammation through classical (CB1, CB2), and non-classical pathways [(TRP channels; TRPV1, TRPA1), PPAR-γ), and orphan GPCRs (GPR55, GPR18)]. They engage interconnected signalling networks rather than a single dominant mechanism, collectively influencing immune cell function.”

https://www.sciencedirect.com/science/article/abs/pii/S0006295226003655?via%3Dihub

“List of Autoimmune Diseases”

https://www.ncbi.nlm.nih.gov/books/NBK605867


Acute anti-proliferative and anti-migratory effects of cannabidiol on C6 rat glioma, SH-SY5Y human neuroblastoma, and HT22 mouse hippocampal neuronal cell cultures

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“Background: The treatment of central nervous system tumors remains challenging owing to their highly proliferative nature, aggressiveness, and poor prognosis. Additionally, existing treatment methods have several problems, including high risk of complications, systemic side effects, and impact on patients’ quality of life. Recently, cannabidiol (CBD), a non-psychoactive cannabinoid found in Cannabis sativa, has emerged as an alternative therapeutic medication because of its potential antitumor activity with fewer side effects.

Methods: We evaluated the cell viability, clonogenicity, migration, apoptotic nuclear morphology, and cell cycle phases of C6 rat glioma, SH-SY5Y human neuroblastoma, and HT22 immortalized mouse hippocampus neuronal cultures treated with CBD ranged between 0 and 10 μg/mL.

Results: CBD concentrations exceeding 5 μg/mL induced significant reductions in cell viability in C6 glioma and SH-SY5Y neuroblastoma cultures, accompanied by decreased clonogenicity in both cultures at 10 μg/mL. A scratch assay for cell migration revealed that 5 μg/mL CBD suppressed C6 glioma cell migration. Additionally, late apoptotic nuclear morphology was observed in C6 glioma cultures treated with 10 μg/mL cannabidiol. Similarly, HT22 hippocampal neuronal cultures exhibited decreased cell viability and clonogenicity, with apparent nuclear signs of apoptosis at CBD concentrations over 5 μg/mL. Notably, CBD disrupted HT22 cell migration at concentrations of 2.5 and 5 μg/mL. Proteomic profiling of C6 glioma revealed upregulation of ribosomal proteins, molecular chaperones, and modulators of cytoskeletal dynamics upon treatment with 1 μg/mL CBD. In comparison, treatment with 2.5 μg/mL CBD led to marked downregulation of endoplasmic reticulum chaperones, mitochondrial ATP synthase, and cytoskeletal regulators.

Conclusion: Our findings confirm the sensitivity of glioma, neuroblastoma, and hippocampal neuronal cultures to CBD, providing valuable insights for further research into its therapeutic potential against glioma, neuroblastoma, and neuronal disorders.”

https://pubmed.ncbi.nlm.nih.gov/42088408

“Our findings demonstrate that CBD exerts dose-dependent anti-proliferative effects across all three cell lines, with tumor cells and neuronal cells exhibiting comparable sensitivity at higher concentrations.”

https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2026.1727831/full

Cannabinoids for Dermatological Applications: Mechanistic Insights, Clinical Evidence, and Emerging Nanotechnology-Enabled Delivery Strategies

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“Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin penetration, and inconsistent bioavailability.

At the molecular level, CBs modulate keratinocyte proliferation, sebocyte activity, fibroblast function, melanocyte balance, and immune signalling through CB1/CB2 receptors, TRP channels, and PPARγ pathways.

Evidence supports their potential in the treatment of psoriasis, atopic dermatitis, acne, allergic contact dermatitis, pruritus, scleroderma, and skin cancers. Clinical evidence remains preliminary: topical and oral formulations have demonstrated anti-inflammatory, antiproliferative, antibacterial, and antifibrotic effects, with improvements in pruritus, lesion severity, and quality of life in early-phase studies. However, most trials are small, uncontrolled, and lack placebo comparators, limiting generalisability.

To overcome formulation barriers and enhance dermal delivery, advanced pharmaceutical strategies such as liposomes, nanoemulsions, polymeric nanoparticles, micelles, and transdermal systems have been investigated to improve stability, controlled release, and targeted skin deposition while minimising systemic exposure.

This review integrates mechanistic insights, clinical evidence, and emerging nanotechnology-enabled delivery approaches, emphasising rational formulation design and translational considerations necessary for advancing CBs toward standardised and clinically reliable dermatological therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/42076122

“In summary, cannabinoids represent a biologically plausible yet clinically evolving therapeutic class in dermatology. Advancing their role in patient care will depend on coordinated progress in mechanistic understanding, pharmaceutical design, and structured clinical validation.”

https://www.mdpi.com/1999-4923/18/4/469

Cannabigerol (CBG) Modulates Neutrophil Activity and Ameliorates Rheumatoid Arthritis Pathogenesis

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“Background/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. 

Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. 

Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-α and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1β by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1β cytokines in the joints by 22% and 38%, respectively. 

Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning.”

https://pubmed.ncbi.nlm.nih.gov/42075816

“So far, these findings highlight CBG as an effective preclinical modulator candidate for affecting neutrophil-mediated immune responses and attenuating inflammation in rheumatoid arthritis.”

https://www.mdpi.com/1424-8247/19/4/560

Molecular Dynamics and Solvated Interaction Energy Prioritize Cannabidiol and Cannabinol as Variant-Spanning SARS-CoV-2 RBD-ACE2 Interface Blockers

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“Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells when the spike receptor-binding domain (RBD) engages angiotensin-converting enzyme 2 (ACE2).

Cannabinoid scaffolds have recently been reported to bind S1/RBD, block spike-mediated membrane fusion, and modulate host inflammatory pathways, making them attractive candidates for entry inhibition.

Here, we applied an integrated computational pipeline to prioritize cannabis-derived compounds as interfacial blockers of the RBD-ACE2 complex across variants.

Eleven phytocannabinoids were docked into the wild-type (WT) RBD-ACE2 interface, identifying three cavities, with ligands preferentially occupying pocket 1. Complexes were subjected to triplicate 200 ns all-atom molecular dynamics (MD) simulations for WT, Delta, and Omicron BA.1 RBD-ACE2. Binding energetics were quantified using molecular mechanics/generalized Born surface area (MM/GBSA) and solvated interaction energy (SIE), and per-residue contributions were analyzed together with solvent-accessible surface area (SASA) and residue interaction networks.

Among all compounds, cannabidiol (CBD) and cannabinol (CBN) were the only ligands that remained stably bound in pocket 1 for all variants. CBN showed the most favorable ligand-complex binding in WT, whereas CBD preserved favorable binding in Omicron BA.1 despite reduced interface burial, indicating that van der Waals/electrostatic complementarity and solvation, rather than surface coverage alone, govern affinity. Both ligands weakened modeled RBD-ACE2 binding by perturbing hot-spot residues centered on Y505 or N501Y in RBD and E37, A387, and R393 in ACE2.

Overall, our results highlight CBD and CBN as tractable, variant-spanning interface disruptors and illustrate how MD-based free-energy calculations can support computational drug discovery against evolving viral protein-protein interfaces.”

https://pubmed.ncbi.nlm.nih.gov/42075932

“Together, these docking results support the hypothesis that specific phytocannabinoids can effectively occupy critical interface pockets of the RBD/ACE2 complex, with potential to sterically hinder or allosterically modulate spike–receptor recognition.”

https://www.mdpi.com/1420-3049/31/8/1253

CBD Promotes Structural and Functional Epithelial Restoration and Alleviates Inflammation in a Mouse Model of Interstitial Cystitis

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“Background: Interstitial cystitis (IC) is a debilitating lower urinary tract condition characterised by chronic inflammation of the bladder. As the aetiology remains unknown, current treatments are symptomatic, aiming to reduce inflammation and pain. Cannabidiol (CBD), the most common cannabinoid in industrial Cannabis sativa (hemp), is one of the most important pharmacologically active cannabinoids used in medicine due to its anti-inflammatory and antioxidant effects without psychoactive properties. While other cannabinoids have shown beneficial effects in animal models of IC, the impact of CBD on the urinary bladder and overall animal well-being has not been elucidated. 

Methods: Using a cyclophosphamide (CYP)-induced mouse model of IC, we investigated the effects of intraperitoneally administered CBD on bladder structure, function, inflammation, and animal behaviour. A multimodal approach was applied, including light and electron microscopy, immunolabeling, qPCR, transepithelial electrical resistance (TEER) measurements, behavioural testing, and monitoring of animals. 

Results: CBD treatment promoted the restoration of damaged urothelial structure and improved the integrity of the blood-urine barrier. Additionally, CBD exerted an anti-inflammatory effect, reducing oedema and infiltration of inflammatory cells in the bladder wall with chronic cystitis. Finally, the increased burrowing activity of CBD-treated mice suggests a benefit of CBD on overall well-being. 

Conclusions: Our findings suggest that CBD has a beneficial effect on the inflamed urinary bladder and could potentially serve as an adjunct treatment for patients with IC in the future.”

https://pubmed.ncbi.nlm.nih.gov/42076110

“Overall, the beneficial effects of CBD were observed at several levels: on damaged urothelial structure, compromised bladder barrier function, chronic bladder inflammation, and the well-being of the experimental animals.”

https://www.mdpi.com/1999-4923/18/4/458

Pharmacological Insights into Cannabidiol for Wound Healing and Bone Regeneration

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“Cannabidiol (CBD), a major nonpsychoactive phytocannabinoid derived from Cannabis sativa L., has recently gained prominence for its broad pharmacological profile and emerging applications in regenerative medicine.

Beyond its well-established neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic, and anticancer effects, CBD has demonstrated the capacity to modulate key biological processes involved in tissue repair. Increasing evidence indicates that CBD promotes wound healing by regulating inflammatory responses, cellular proliferation, and extracellular matrix remodeling through interactions with cannabinoid and noncannabinoid receptors expressed in neural, immune, and epithelial cells.

Notably, these receptors are also present in osteogenic and progenitor cells, suggesting that CBD may influence bone metabolism and regeneration. Recent preclinical studies have reported that CBD enhances osteoblastic differentiation, angiogenesis, and matrix mineralization, highlighting its potential as a bioactive molecule for bone tissue engineering.

Within the dental field, such properties open new perspectives for the development of CBD-based biomaterials aimed at improving osseointegration, soft tissue healing, and the overall biological performance of implantable devices.

Accordingly, this review aims to provide a comprehensive overview of the pharmacological and molecular mechanisms underlying the effects of CBD on wound healing and bone regeneration. Furthermore, it discusses dose-response relationships, delivery routes, formulation strategies, and the current legal and regulatory frameworks influencing CBD translation into clinical dental applications.

These insights may support the rational design of next-generation bioactive materials incorporating CBD for oral and maxillofacial regenerative therapies.”

https://pubmed.ncbi.nlm.nih.gov/42077915

“In conclusion, this critical review examined the biological mechanisms through which cannabidiol (CBD) may contribute to wound healing and bone repair/regeneration. Current preclinical evidence supports the therapeutic potential of CBD in enhancing both soft- and hard-tissue repair by modulating key molecular pathways involved in inflammation, cellular proliferation, angiogenesis, and extracellular matrix remodeling.”

https://pubs.acs.org/doi/10.1021/acsomega.5c13259

Modulation of the endocannabinoid system reduces inflammatory signalling in canine mammary carcinoma cells

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“Background: Canine mammary carcinoma (CMC) is characterised by a chronic inflammatory microenvironment resembling human breast cancer; however, the upstream regulatory mechanisms driving this phenotype remain unclear. The endocannabinoid system (ECS) has emerged as a potential modulator of inflammation and tumour biology. This study investigated the role of the ECS in CMC and evaluated the anti-inflammatory effects of cannabidiol (CBD).

Methods: Primary cell cultures were established from surgically excised CMC tissues, with matched normal mammary epithelium used as controls. Basal mRNA expression of ECS-related receptors (CB1, CB2, transient receptor potential vanilloid 1 [TRPV1], G-protein-coupled receptor 55 [GPR55] and peroxisome proliferator-activated receptor alpha [PPAR-α]) and inflammatory mediators (COX-1, COX-2, interleukin [IL]-4, IL-6, IL-33, IL-17A, tumour necrosis factor-alpha [TNF-α] and LCN2) was assessed by reverse transcription quantitative polymerase chain reaction. Cytokine secretion (IL-6, IL-8, TNF-α and IL-17A) was quantified by enzyme-linked immunosorbent assay. Cell viability assays were performed to determine the 24-h IC50 of CBD (32 µM), and sub-cytotoxic concentrations (3, 10 and 20 µM) were subsequently applied for 24 h.

Results: Canine mammary carcinoma-derived cells exhibited significant overexpression of ECS receptors (CB1, CB2, TRPV1, GPR55 and PPAR-α) compared to normal controls. These cells also showed increased secretion of pro-inflammatory cytokines, including IL-6, IL-8, TNF-α and IL-17A. Treatment with CBD at 10-20 µM significantly downregulated key inflammatory genes, particularly COX-2, IL-6 and TNF-α, and reduced corresponding cytokine release without compromising cell viability.

Conclusion: The ECS is upregulated in CMC and appears to contribute to the inflammatory tumour microenvironment. Cannabidiol effectively attenuates this inflammatory phenotype at sub-cytotoxic concentrations, supporting its potential as a therapeutic agent in CMC.”

https://pubmed.ncbi.nlm.nih.gov/42078490

“These findings may also have relevant implications for human health, as CMC shares key molecular and pathological features with human breast cancer. Therefore, the modulation of ECS-related pathways observed in this study may reflect conserved mechanisms that could be exploited for the development of novel anti-inflammatory and anti-tumour strategies in human oncology.”

https://bvajournals.onlinelibrary.wiley.com/doi/10.1002/vro2.70034

The Effect of Cannabidiol on Cancer-Pathway Genes in Doxorubicin-Sensitive and Resistant Breast Cancer Cells

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“Purpose: Cannabidiol (CBD) is a primary bioactive, non-intoxicating cannabinoid found in the cannabis plant. Studies have shown that CBD causes anticancer activity by inhibiting the expression of growth factors and inducing apoptosis, leading to cell cycle arrest. In this study, we aimed to determine how CBD influences the expression of genes that affect cancer pathways in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) breast cancer cells. 

Materials and Methods: IC50 concentrations of CBD in MCF-7 and MCF-7/Adr cell lines were determined by the MTT cell cytotoxicity assay. RNA isolation and subsequent cDNA synthesis were performed for qPCR experiments with the determined IC50 values. The effects of CBD on the cell cycle and apoptosis were studied using flow cytometry. IC50 values of CBD were determined in MCF-7 and MCF-7/Adr breast cancer cell lines at eight different concentrations and at three different incubation periods (24 h, 48 h, and 72 h) with different doses. RT-qPCR was used to investigate the molecular mechanisms underlying the expression of genes involved in cancer pathway analysis. 

Results: Treatment with CBD at concentrations of 17.57 μM (MCF-7) and 11.41 μM (MCF-7/Adr) for 48 h decreased colony formation, induced apoptosis, and inhibited cell invasion in both cell lines. In addition, we observed significant alterations of angiogenesis, apoptosis, cell cycle, cellular senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, metabolism, telomeres, and telomerase in both cell lines. 

Conclusions: Our research indicates that CBD could be an effective natural bioactive compound for breast cancer treatment, inhibiting tumor cell proliferation and inducing apoptosis.”

https://pubmed.ncbi.nlm.nih.gov/42075870

“The plant Cannabis sativa has been used medicinally for several thousand years.”

“These findings support the relevance of CBD as a potential therapeutic agent in breast cancer and provide a basis for further investigation “

https://www.mdpi.com/1424-8247/19/4/615