Search Results (93)

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

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 Il1b, Il4, Il6, Il13, Il22, Il31, Tlr2, Vegfa, 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. Full article

Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart’s energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency. A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors—CB₁ and CB₂, α2 adrenoceptor, or 5-hydroxytryptamine receptor. Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas–liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method. Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium. The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction. Full article

The increasing environmental and health concerns associated with synthetic pesticides underscore the need for sustainable alternatives in pest management. This study investigates the chemotactic responses of five nematode species—Heterorhabditis bacteriophora, Steinernema carpocapsae, Steinernema feltiae, Phasmarhabditis papillosa, and Oscheius myriophilus—to three major cannabinoids from Cannabis sativa: Δ⁹-tetrahydrocannabinol (THC), cannabigerol (CBG), and cannabidiol (CBD). Using a standardized chemotaxis assay, we quantified infective juvenile movement and calculated Chemotaxis Index (CI) values across varying cannabinoid concentrations. Our results revealed strong species-specific and dose-dependent responses. THC and CBG elicited significant attractant effects in P. papillosa, S. feltiae, and H. bacteriophora, with CI values ≥ 0.2, indicating their potential as behavioral modulators. In contrast, CBD had weaker or repellent effects, particularly at higher concentrations. O. myriophilus exhibited no consistent response, underscoring species-specific variation in chemosensory sensitivity. These findings demonstrate the potential utility of cannabinoids, especially THC and CBG, as biocompatible cues to enhance the efficacy of nematode-based biological control agents in integrated pest management (IPM). Further field-based studies are recommended to validate these results under realistic agricultural conditions. Full article

Malignant gliomas, including glioblastoma multiforme (GBM), are highly aggressive brain tumors with a poor prognosis and limited treatment options. This study investigates the antitumor potential of bioactive compounds derived from Cannabis sativa and Piper nigrum using molecular docking, cell viability assays, and transcriptomic and expression analyses from public databases in humans and cell lines. Cannabichromene (CBC), cannabigerol (CBG), cannabidiol (CBD), and Piper nigrum derivates exhibited strong binding affinities relative to glioblastoma-associated targets GPR55 and PINK1. In vitro analyses demonstrated their cytotoxic effects on glioblastoma cell lines (U87MG, T98G, and CCF-STTG1), as well as on neuroblastoma (SH-SY5Y) and oligodendroglial (MO3.13) cell lines, revealing interactions among these compounds. The differential expression of GPR55 and PINK1 in tumor versus normal tissues further supports their potential as biomarkers and therapeutic targets. These findings provide a basis for the development of novel therapies and suggest unexplored molecular pathways for the treatment of malignant glioma. Full article

Background/Objectives: Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with significant therapeutic potential, showing emerging applications in drug delivery. This study aimed to develop and evaluate CBG-conjugated nanoparticles (NPs) incorporating tubulin-targeting drugs to enhance anticancer activity. Methods: CBG was conjugated with N-desacetylthiocolchicine, paclitaxel, and camptothecin using sebacic acid and 4,4′-dithiodibutyric acid as linkers, and nanoparticles were obtained. The NPs were characterized by their stability and size (hydrodynamic diameters < 90 nm). Their antiproliferative activity was assessed in three human tumor cell lines and non-tumorigenic cells. Their cellular uptake and mechanisms of action were investigated via confocal microscopy and cell cycle analysis. Results: The chemical composition of the linkers significantly influenced the antiproliferative effect, with the NPs containing 4,4′-dithiodibutyric acid demonstrating higher activity. Notably, NP3b, formulated with this linker, exhibited up to an 80-fold increase in antiproliferative potency compared to its sebacic acid counterpart (NP3a). In mesothelioma cells (MSTO-211H), NP3b displayed significantly higher cytotoxicity than in non-tumorigenic mesothelial cells (MeT-5A), indicating selectivity for cancer cells. Further analysis in glioblastoma cells confirmed that the NPs retained the microtubule-disrupting effects of their parent drugs. Conclusions: These findings highlight the potential of CBG-based NPs as versatile nanomedicine platforms for targeted cancer therapy. This study underscores the importance of linker chemistry in modulating therapeutic efficacy and supports the development of multifunctional drug delivery systems. Full article

Background and Aims: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its effects in females remain unknown. Given immune cell population changes in MASLD patients, this study examines CBG’s impact on methionine-choline deficient (MCD) diet-induced MASH in female mice. Methods: MCD-fed female mice are supplemented with two different doses for three weeks. Liver fibrosis, steatosis, oxidative stress, ductular reaction, and inflammation are assessed via Sirius Red, Oil Red O, immunohistochemistry, and immunofluorescence staining. Immune cell changes in non-parenchymal cells (NPCs) are analyzed via flow cytometry. Results: CBG treatment improves liver health by reducing leukocyte infiltration. Both CBG doses significantly decrease fibrosis, oxidative stress, ductular proliferation, and inflammation in MCD-fed mice, including monocyte and T lymphocyte reductions. Additionally, CBG downregulates mast cell activation, inhibiting transforming growth factor (TGF)-β1 release, thereby suppressing hepatic stellate cell activation. This reduces collagen deposition, fibrosis, and ductular proliferation. Conclusions: Our findings provide insights for pre-clinical and clinical research, highlighting CBG’s potential therapeutic role and dosage considerations in mitigating liver fibrosis and inflammation in female patients. Full article

The inflammatory state is a significant factor associated with diabetic kidney disease (DKD), making it one of the significant causes of chronic kidney disease. Despite the availability of data, there is a lack of targeted treatment strategies for diabetes-related kidney disorders. The aim of our study was to determine the impact of cannabigerol (CBG) on lipid precursors for inflammatory mediators during DKD development. A six-week experiment was conducted on male Wistar rats fed standard (Control) or high-fat high-sucrose (HFHS) diets. For the last 14 days of the experiment (5th and 6th weeks), half of the rats from the Control and HFHS groups intragastrically received CBG solution. Gas–liquid chromatography (GLC) was used to measure the activities of n-6 and n-3 polyunsaturated fatty acid (PUFA) metabolic pathways and the concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in selected lipid fractions. Immunoblotting was performed to assess the expression of proteins involved in the regulation of the inflammatory state. A multiplex immunoassay kit was used to determine kidney toxicity biomarker levels. Our results revealed that CBG administration to rats fed an HFHS diet decreased n-6 PUFA biosynthetic pathway activity in phospholipid (PL) and triacylglycerol (TAG) and increased n-3 PUFA biosynthetic pathway activity in TAG and free fatty acid (FFA). We also observed a reduction in the AA concentration in PL, FFA, and diacylglycerol (DAG). CBG supplementation reduced the level of kidney damage biomarkers, such as osteopontin (OPN). Our observations confirm that CBG has potential anti-inflammatory properties and may be successfully used for further research to seek targeted therapies of inflammatory disorders, including diabetic kidney disease progression. Full article

Cannabinoids are widely recognized for their potential therapeutic effects, making them significant and valuable candidates for medical research and applications across various fields. This review aims to analyze the pharmacokinetics of Cannabidiol (CBD), Cannabigerol (CBG), and Cannabichromene (CBC), along with their corresponding acidic forms, Cannabidiolic acid (CBDA), Cannabigerolic acid (CBGA), and Cannabichromenic acid (CBCA). Among these cannabinoids, CBD is the most extensively studied. Nevertheless, research involving all the mentioned cannabinoids has shown that their pharmacokinetic parameters are highly variable, depending significantly on factors such as dose, formulation, route of administration, and diet. Furthermore, challenges such as brain penetration and first-pass metabolism have been highlighted. In conclusion, this review demonstrates significant progress in understanding the pharmacokinetics of non-psychotropic cannabinoids. However, it also underscores the need for further research, particularly on CBG, CBC, and their respective acidic forms, with the most significant gap being in clinical investigations. Expanding these studies is essential to facilitate their optimized use in medical treatments. Full article

Cannabinoid compounds have potential as treatments for a variety of conditions, with cannabigerol (CBG) being known for its anti-inflammatory properties. In this study, we investigated the effects of CBG in a cellular model of 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD). In the cellular model, we confirmed the cytotoxicity of CBG and downregulated the expression of inflammatory markers CCL26, IL1B, IL6, and TNF (p < 0.001). In the mouse model, clinical, histological, and immunological changes were analyzed. The results showed that CBG improved dermatitis severity score, epidermal thickness, and mast cell count and reduced inflammatory cytokines (Tslp, Il1b, Il4, Il6, Il13, Il17, Il18, Il22, and Il33) by qRT-PCR (p < 0.001). Western blot results showed modulated changes in JAK1, JAK2, TYK2, STAT1, STAT2, STAT3, p-STAT3, STAT6, and p-STAT6 (p < 0.05). Subsequently, p-IκBα, NF-κB, and p-NF-κB signaling factors were also reduced (p < 0.05), with corresponding changes in skin barrier factors. The results of this study indicate that CBG effectively alleviates AD-like symptoms and suggest the potential of CBG as a therapeutic agent. Full article

Several cannabis plant-derived compounds, especially cannabinoids, exhibit therapeutic potential in numerous diseases and conditions. In particular, THC and CBD impart palliative, antiemetic, as well as anticancer effects. The antitumor effects include inhibition of cancerous cell growth and metastasis and induction of cell death, all mediated by cannabinoid interaction with the endocannabinoid system (ECS). However, the exact molecular mechanisms are still poorly understood. In addition, their effects on leukemia have scarcely been investigated. The current work aimed to assess the antileukemic effects of CBN and CBG on an acute monocytic leukemia cell line, the THP-1. THP-1 cell viability, morphology and cell cycle analyses were performed to determine potential cytotoxic, antiproliferative, and apoptotic effects of CBN and CBG. Western blotting was carried out to measure the expression of the proapoptotic p53. Both CBN and CBG inhibited cell growth and induced THP-1 cell apoptosis and cell cycle arrest in a dose- and time-dependent manner. CBN and CBG illustrated different dosage effects on THP-1 cells in the MTT assay (CBN > 40 μΜ, CBG > 1 μM) and flow cytometry (CBN > 5 μM, CBG > 40 μM), highlighting the cannabinoids’ antileukemic activity. Our study hints at a direct correlation between p53 expression and CBG or CBN doses exceeding 50 μM, suggesting potential activation of p53-associated signaling pathways underlying these effects. Taken together, CBG and CBN exhibited suppressive, cell death-inducing effects on leukemia cells. However, further in-depth research will be needed to explore the molecular mechanisms driving the anticancer effects of CBN and CBG in the leukemia setting. Full article

Due to the typical production of Cannabis sativa L. for medical use in an artificial environment, it is crucial to optimize environmental and nutritional factors to enhance cannabinoid yield and quality. While the effects of light intensity and nutrient composition on plant growth are well-documented for various crops, there is a relative lack of research specific to Cannabis sativa L., especially in controlled indoor environments where both light and nutrient inputs can be precisely manipulated. This research analyzes the effect of different light intensities and nutrient solutions on growth, flower yield, and cannabinoid concentrations in seeded chemotype III cannabis (high CBD, low THC) in a controlled environment. The experiment was performed in a licensed production facility in the Czech Republic. The plants were exposed to different light regimes during vegetative phase and flowering phase (light 1 (S1), photosynthetic photon flux density (PPFD) 300 µmol/m²/s during vegetative phase, 900 µmol/m²/s in flowering phase and light 2 (S2) PPFD 500 µmol/m²/s during vegetative phase, 1300 µmol/m²/s during flowering phase) and different nutrition regimes R1 (fertilizer 1) and R2 (fertilizer 2). Solution R1 (N-NO₃⁻ 131.25 mg/L; N-NH₄⁺ 6.23 mg/L; P₂O₅ 30.87 mg/L; K₂O 4112.04 mg/L; CaO 147.99 mg/L; MgO 45.68 mg/L; SO₄²⁻ 45.08 mg/L) was used for the whole cultivation cycle (vegetation and flowering). Solution R2 was divided for vegetation phase (N-NO₃⁻ 171.26 mg/L; N-NH₄⁺ 5.26 mg/L; P₂O₅ 65.91 mg/L; K₂O 222.79 mg/L; CaO 125.70 mg/L; MgO 78.88 mf/L; SO₄²⁻ 66.94 mg/L) and for flowering phase (N-NO₃⁻ 97.96 mg/L; N-NH₄⁺ 5.82 mg/L; P₂O₅ 262.66 mg/L; K₂O 244.07 mg/L; CaO 138.26 mg/L; MgO 85.21 mg/L; SO₄²⁻ 281.54 mg/L). The aim of this study was to prove a hypothesis that light will have a significant impact on the yield of flowers and cannabinoids, whereas fertilizers would have no significant effect. The experiment involved a four-week vegetative phase followed by an eight-week flowering phase. During the vegetative and flowering phases, no nutrient deficiencies were observed in plants treated with either nutrient solution R1 (fertilizer 1) or R2 (fertilizer 2). The ANOVA analysis showed that fertilizers had no significant effect on the yield of flowers nor cannabinoids. Also, light intensity differences between groups S1 (light 1) and S2 (light 2) did not result in visible differences in plant growth during the vegetative stage. However, by the fifth week of the flowering phase, plants under higher light intensities (S2—PPFD 1300 µmol/m²/s) developed noticeably larger and denser flowers than plants in the lower light intensity group (S1). The ANOVA analysis also confirmed that the higher light intensities positively influenced cannabidiol (CBD), tetrahydrocannabinol (THC), cannabigerol (CBG), and cannabichromene (CBC) when the increase in the concentration of individual cannabinoids in the harvested product was 17–43%. Nonetheless, the study did not find significant differences during the vegetative stage, highlighting that the impact of light intensities is phase-specific. These results are limited to controlled indoor conditions, and further research is needed to explore their applicability to other environments and genotypes. Full article

The study highlights the need for quality control in evaluating medicinal plant products, especially CBD oils, before market release. Due to varying regulatory requirements, product labeling can sometimes be misleading, especially regarding cannabinoid concentrations such as CBD and THC. This research focused on developing a validated high-performance liquid chromatography (HPLC) method for accurately identifying and quantifying key cannabinoids in Commercial Veterinary CBD Oil. The main compounds identified included Cannabidivarin (CBDV), Cannabidiolic Acid (CBD-A), Cannabigerolic Acid (CBG-A), Cannabigerol (CBG), Cannabidiol (CBD), Tetrahydrocannabivarin (THCV), Cannabinol (CBN), ∆⁹-Tetrahydrocannabinol (d9-THC) ∆8-Tetrahydrocannabinol (d8-THC), Cannabicyclol (CBL), Cannabichromene (CBC), and Tetrahydrocannabinolic Acid (THCA), determined in line with the International Conference on Harmonization’s (ICH) guidelines. The method was validated for linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ). It was determined to be linear, with a correlation coefficient (R²) > 0.999. The LOD and LOQ values calculated from the calibration curve ranged from 0.05 to 0.13 and 0.50 to 0.61 µg/mL, respectively. The method also exhibited acceptable precision, with relative standard deviation values lower than or equal to 2%. The method’s accuracy was assessed through recovery percentages and fell within an acceptable range of 98–102 if the RSD was 2%. This study’s rigorous methodology and comprehensive findings significantly contribute to cannabinoid analysis. This validated protocol was used to analyze cannabinoids in 14 commercial veterinary CBD oil products from the Republic of North Macedonia. The performance parameters demonstrated that the method is reliable for quantitatively measuring cannabinoids in CBD oil. The analysis showed that the cannabinoid levels in the products were consistent with the manufacturers’ declared specifications, with no significant discrepancies in labeling. Full article

In Europe, industrial hemp (Cannabis sativa L.) is currently cultivated primarily for its fibers and seeds due to regulatory restrictions on flower use, although the flowers present untapped valorization potential. This study assesses the economic viability of cultivating hemp for its inflorescences and examines the quality impact of different cultivation methods by testing two varieties, Santhica 27 and Félina 32, across distinct growth environments. The cultivation systems tested include greenhouse-based soilless setup and open-field production. Within the greenhouse, the effects of an ethylene-based growth regulator, applied during the vegetative stage, on plant morphology and cannabinoid concentrations were assessed at three dosage levels (7.5, 15, and 30 µL L⁻¹). The results showed a dose-dependent reduction in shoot height, lasting 21 to 28 days post-treatment before diminishing. Comparable total cannabigerol (CBG) levels were achieved with Santhica 27 in both field conditions and at the 30 µL L⁻¹ ethylene dose in the greenhouse, while total cannabidiol (CBD) levels in Félina 32 were higher in the field than in the greenhouse. Overall, greenhouse cultivation yielded significantly greater cannabinoid production per square meter due to increased inflorescence biomass and the potential for multiple harvest cycles. However, operating costs for greenhouse cultivation are at least 13 to 15 times higher than those of open-field production. Economic analysis suggests that optimizing greenhouse cultivation techniques and reducing labor requirements at harvest could help mitigate these costs, enhancing the economic feasibility of greenhouse-based hemp flower production. Full article

Cannabigerol (CBG), a non-psychoactive cannabinoid found in cannabis, has emerged as a promising therapeutic agent with a diverse range of potential applications. Unlike its well-known counterpart tetrahydrocannabinol (THC), CBG does not induce intoxication, making it an attractive option in the clinic. Recent research has shed light on CBG’s intriguing molecular mechanisms, highlighting its potential to modulate multiple physiological processes. This review delves into the current understanding of CBG’s molecular interactions and explores its therapeutic power to alleviate various conditions, including cancer, metabolic, pain, and inflammatory disorders, amongst others. We discuss how CBG interacts with the endocannabinoid system and other key signaling pathways, such as CB1, CB2, TPR channels, and α2-adrenoceptor, potentially influencing inflammation, pain, neurodegeneration, and other ailments. Additionally, we highlight the ongoing research efforts aimed at elucidating the full spectrum of CBG’s therapeutic potential and its safety profile in clinical settings. Through this comprehensive analysis, we aim to provide a deeper understanding of CBG’s role in promoting human health and pave the way for future research endeavors. Full article