“The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB1 receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system.
In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration.
Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP).”
“To develop effective therapies for conditions with defective endocannabinoid system (ECS) activity, it is essential to understand the skeletal ECS’s function in health and disease. Here, we present a detailed functional and molecular characterization of a transgenic mouse model with skeletal muscle-specific Cnr1 genetic ablation.
Our in vivo results demonstrate that CB1R knockdown impairs motor coordination and grip strength in mice. Furthermore, at the cellular level, we observed modestly altered calcium homeostasis and significantly decreased mitochondrial function (decreased complex IV activity). Therefore, we propose that the ECS (particularly CB1R) plays a key role in physiological muscle force generation and in maintaining cellular and mitochondrial homeostasis and function.”
“Mesenchymal stem cells isolated from human adipose tissue (hASCs) are a promising tool for tissue repair due to their ability to differentiate into specific cell lineages. The possibility of modulating the adipogenic differentiation of hASCs is crucial in improving their therapeutic potential.
This study aimed to investigate the effects of cannabidiol (CBD), a phytocannabinoid isolated from Cannabis sativa L., on hASCs. Few studies have evaluated its role in stem cell (SC) properties and their differentiation potential.
hASCs were first treated with different concentrations of CBD (ranging from 0.1 to 10 μM) to assess its effects on viability, demonstrating that this molecule is non-toxic, except at the concentration of 10 μM. Subsequently, the role of CBD in the proliferation, metabolism and adipogenic potential of hASCs was analyzed.
CBD promoted adipogenesis in a dose-dependent manner, even in the absence of differentiation medium. This result was evidenced by the presence of lipid vacuoles, the expression of adipogenic markers, cytoskeletal actin rearrangement and modulation in the expression of osteogenic genes.
Although the results indicated a role of CBD in promoting hASC adipogenesis, further research will be needed to explore the mechanism of action of CBD in SC differentiation and to deepen its utility in SC-based approaches.”
“Therefore, as the field of regenerative medicine continues to evolve, the integration of CBD’s properties into therapeutic strategies could hold significant promise in terms of enhancing tissue repair and recovery, offering novel strategies for optimizing healing outcomes and improving patient well-being.”
“Fungal infections pose a major threat to human health with increasing incidence of antifungal resistance globally. Despite the need for novel antifungal drugs, few are currently in clinical development.
Here we evaluate the antifungal activity of five phytocannabinoids against several clinically relevant fungal pathogens, with a focus on the priority pathogen Cryptococcus neoformans.
Our results demonstrate that Cannabidiol (CBD), and particularly Cannabidivarin (CBDV), have broad activity against C. neoformans and other fungal pathogens, including dermatophytes that cause common tinea. We found that both CBD and CBDV acted in a fungicidal manner and prevented biofilm formation in C. neoformans.
Phytocannabinoid treatment impeded factors important for virulence and antifungal resistance, including reduced capsule size and disruption of mature biofilms. Proteomics analysis revealed that the antifungal activity of CBD and CBDV was linked to destabilisation of the membrane, alterations in ergosterol biosynthesis, disruption of metabolic pathways, as well as selective involvement of mitochondrial-associated proteins. We next tested the ability of CBD to topically clear a C. neoformans fungal infection in vivo using the Galleria mellonella burn wound model, and we observed greatly improved survival in the CBD treated larvae.
This study illustrates the potential of phytocannabinoids as antifungal treatments and opens up new routes towards development of novel antifungal drugs.”
“Fungal infections are a major public health issue affecting over a billion people globally. Current antifungal treatments are increasingly compromised by drug resistance and show adverse side effects, underscoring the urgent need for novel therapies.
Phytocannabinoids like Cannabidiol (CBD) and Cannabidivarin (CBDV), which have established safety profiles and are approved or under investigation for neurological conditions, may hold promise in this domain. Despite this, their antifungal properties remain underexplored.
Here we show that CBD and CBDV exhibit in vitro antifungal activity against various fungi, including common dermatophytes causing “jock itch” and “athlete’s foot”, as well as WHO Critical Priority pathogens, such as Cryptococcus neoformans. Further investigation in C. neoformans revealed that CBD and CBDV appear to work by disrupting biofilms, altering fungal cell morphology, and impacting metabolic pathways and membrane integrity, as observed through comparative proteomics. Further, in vivo experiments using Galleria mellonella infected with C. neoformans revealed significantly improved survival with CBD treatment.
The in vitro and in vivo antifungal efficacy of CBD and CBDV established in this study highlights the potential of phytocannabinoids to address the pressing need for effective and new treatments for fungal infections.”
“Overall, this study highlights promising antifungal properties of the phytocannabinoids CBD and CBDV against select fungal pathogens. We demonstrated not only their fungicidal activity against C. neoformans, but also their potential effectiveness against wider Cryptococcus strains, various other yeasts, and moulds including common dermatophytes, emphasizing their potential broader applicability in the clinic and the community.
We demonstrated that the phytocannabinoids appear to work via disrupting biofilms and altering cell morphology, while clear impacts on metabolism and membrane production could be observed with comparative proteomics. We finally showed that for the commonly available CBD, in vivo survival of G. mellonella was significantly boosted after C. neoformans infection, emphasizing the clear potential of CBD as an antifungal.
Taken together, the demonstrated efficacy of CBD and CBDV as broad antifungal agents, coupled with their established safety profile, makes them an exciting resource as a foundation for the development of future therapeutic interventions.”
“This study examined the xanthine oxidase (XO) inhibitory potential of hemp protein hydrolysates, prepared using various proteases.
The hydrolysate derived from neutral protease showed the strongest XO inhibition (IC50 = 0.99 ± 0.31 mg/mL) and significantly reduced serum uric acid, creatinine, and urea nitrogen levels in hyperuricemia mice while enhancing renal histopathology.
LC-MS/MS identified three novel XO-inhibitory peptides (AMRAMPDDVLAN, NNYNLPIL, KTNDNAWVSPLAG) with IC50 values ranging from 1.34 to 2.81 mM. Molecular docking and dynamics simulations revealed the binding mechanisms through interactions with key catalytic residues, such as Ser876, and the obstruction of the hydrophobic channel.
These findings emphasize the hydrolysate and its bioactive peptides as promising candidates for controlling hyperuricemia.”
“Introduction: Cannabis sativa has been cultivated for over 11,700 years, originating in Central and Southeast Asia, and has been used for medical, recreational, and religious purposes. Among its therapeutic potentials, it is notable for its capacity to alleviate pain, nausea, anxiety, and more. The plant’s primary secondary metabolites are cannabinoids, which interact with the endocannabinoid system to produce these effects. However, due to the dosage variability and the secondary effects associated with a lack of targeted action, their medical use is limited, creating the need for effective delivery systems.
Methodology: This systematic patent review on cannabis drug delivery systems was conducted using patents retrieved from the Espacenet database. The search employed the keywords “Cannabis” and “Delivery,” along with the IPC classification code A61, to filter patents filed between 2012 and 2024. This initial search yielded 99 patents, which were further screened to identify 15 patents that met the inclusion criteria.
Results: Of the selected patents, most originated from the United States, followed by Canada, international patents (WIPO), and China. A notable increase in patent filings occurred in 2022, coinciding with the peak in scientific publications on the topic. This trend indicates a growing interest in the design of cannabis delivery systems.
Discussion: The historical importance and therapeutic potential of Cannabis sativa are welldocumented, yet modern medical use remains restricted due to pharmacokinetic limitations. Delivery systems such as extracellular vesicles, microneedles, and emulsions have been developed to improve the bioavailability and stability of cannabinoids. Extracellular vesicles facilitate targeted, noninvasive delivery of cannabinoids to the central nervous system. Microneedles offer a painless method for transdermal administration, overcoming skin barrier limitations. Emulsions improve the solubility and bioavailability of lipophilic cannabinoids, making them suitable for various administration routes.
Conclusion: Since 2012, there has been considerable growth in patents and publications related to cannabis drug delivery systems, driven by the therapeutic potential of cannabinoids. Innovations in delivery systems like emulsions, microneedles, and extracellular vesicles aim to improve the pharmacokinetics and therapeutic efficacy of cannabis-derived compounds, representing a shift towards medical cannabis applications.”
“The main objective of the present study was to determine the protolytic and coordination properties of two bioactive cannabinoid acids (cannabidiolic acid and cannabigerolic acid) in ethyl alcohol-water mixture (50/50, v/v).
The complexation properties of these acids with copper(II) and zinc(II) ions were determined by potentiometric and ESI-MS methods. UV-Vis absorption spectra for the copper(II) systems confirmed the speciation models with one type of complex indicating coordination with completely deprotonated dinegative ligand molecule. The occurrence of precipitation at lower pH values limited the ability to determine complexes under these conditions.
The research also aimed to identify potential biological and medicinal applications of cannabinoid acids and their complexes with zinc(II). The ability of these compounds to influence the growth of human Hs68 skin fibroblasts and AGS gastric adenocarcinoma cells was investigated. Furthermore, these structures were tested against Helicobacter pylori strains, one of the factors promoting gastric cancer development.
At concentrations that were not-toxic to healthy cells (after dilution of the solutions, the composition of the ethanol/water mixture was approximately 1/99, v/v), the ligands exhibited bacterial inhibitory activity and cytotoxic properties against AGS cancer cells. Zinc(II) complexes, on the other hand, being biologically safe for all cells, had strong antibacterial properties, both inhibitory and bactericidal.”
“Naturally occurring compounds known as plant cannabinoids or phytocannabinoids, responsible for the physiological effects of cannabis, have been used medicinally for thousands of years.”
“The importance of hemp seeds (Cannabis sativa L.) as a nutrient-rich resource in agricultural studies is often underestimated by cannabis farmers, who tend instead to treat them as byproducts.
The purpose of this study was to assess the nutritional composition of Beldiya, a distinct ecotype of hemp seed from the northern regions of Morocco. The proximal composition, mineral content, total phenolic content, tocopherol content, fatty acid profile and lipid health indices of the seeds were assessed.
The results revealed that the ‘Beldiya’ ecotype (Be-ecot) contained 94.08% dry matter, 32.81% oil, 24.84% protein, 27.54% fiber and 4.29% ash. It is rich in total phenolic content (201.88 mg GAE/100 g) and total flavonoid content (69.77 mg QE/100 g). The predominant tocopherol in its oil is γ-tocopherol (409.72 mg/kg), with δ-tocopherol (21.91 mg/kg) and α-tocopherol (18.89 mg/kg), contributing to a total tocopherol content of 450.82 mg/kg.
The main fatty acids in the oil are linoleic acid (51.02%), oleic acid (18.05%), linolenic acid (16.46%) and palmitic acid (7.68%). The ratio of n-6 to n-3 polyunsaturated fatty acids (PUFAs) is 3:1, which corresponds to the recommended dietary balance for these essential fatty acids.
These results highlight the nutritional benefits and balanced composition of hemp seeds, highlighting their potential as valuable edible food sources for promoting a healthy lifestyle.”
“Ethnopharmacological relevance: Cannabis sativa has been traditionally used in Moroccan medicine for centuries, either for its psychoactive or therapeutic effects. However, the safety profile of extracts from macerated leaves remains poorly documented in the scientific literature.
Aim of the study: This study, for the first time, evaluates the phytochemical composition and the toxicological profile of an ethanolic extract of Cannabis sativa (CEE) leaves in mice, focusing on behavioral effects, oxidative stress markers, and histopathological examination.
Materials and methods: The CEE was evaluated using HPLC analysis, secondary metabolites quantification, and in vitro antioxidant assays. Acute oral toxicity was assessed in female mice at doses from 500 to 3000 mg/kg, while oral subacute toxicity was evaluated over 7 days in male mice receiving 10, 30, or 50 mg/kg of CEE. Behavioral assessments included the open field, rotarod, and elevated plus maze tests. Additionally, body weight gain, organ coefficients, organ edema, oxidative stress markers, and histopathology of the brain, liver, kidneys, spleen, and testes were examined.
Results: CEE exhibited substantial amounts of polyphenols, flavonoids, tannins, and saponins, with notable antioxidant activity (DPPH IC50: 289.01 ± 0.003 μg/mL; FRAP IC50: 57.29 ± 6.7 μg/mL). No mortality was observed in the acute toxicity study. The 7-day treatment caused no sedation or motor impairment, rather, it showed anxiolytic effects. A significant increase in body weight gain was noted, particularly at 10 mg/kg, while no changes in organ coefficients or signs of organ edema were detected. However, MDA and catalase activity increased in the liver and brain at 50 mg/kg. Histopathological examination revealed signs of cellular stress without severe tissue damage.
Conclusions: CEE appears to be safe at moderate doses, with an LD50 above 3000 mg/kg. Further studies are needed to assess long-term effects.”
“The ultra-high-performance liquid chromatography high-resolution mass spectrometry (LC-ESI-HR-MS/MS) technique was used to characterize the polyphenolic fraction of the hot water infusion (WI) of inflorescences of Cannabis sativa L. Kompolti variety, commercially used for food preparations or cosmetic purposes.
On water infusion extract, we applied a multidisciplinary approach, where NMR, MS, in vitro cell-free and cell-based assays coupled with in silico studies, were used to rationalize at the molecular level the effects of the major component Cannabidiol (CBD), in a model of Parkinson’s disease (PD). The phytochemical analysis by LC-MS/MS led to the tentative identification of many components belonging to different classes of polyphenols, such as phenolic acids, flavonoids, and their glycosides. CBD and cannabidiolic acid (CBDA) were also detected in good amounts in the infusion, together with several minor cannabinoids. In addition, the water infusion WI was evaluated for mineral content, total phenolic content, flavonoid content, and antioxidant capacity by DPPH and FRAP methods.
Notably, our results in a cellular model of PD highlight that CBD protects against rotenone-induced cell death without recovering neuronal morphology. These biological outcomes were rationalized by an in silico approach, where we hypothesize that CBD could influence the cellular response to oxidative stress via its interaction with the Keap1/Nrf2 pathway.
In summary, these results enriched the nutraceutical profile of the water infusion of the inflorescences of the Kompolti cultivar, which demonstrated a high CBD content.
This study could lead to the development of dietary supplements that could help in the management of clinical symptoms related to the antioxidant activity of CBD in the pathophysiology of PD, which remains poorly characterized.”
“In summary, this multidisciplinary approach has provided further insight into the human health properties of C. sativa L. Kompolti infusions. When consumed as a beverage as part of a normal diet, the phytoconstituents could provide health benefits through their antioxidant activity in various diseases and would be promising for protection against environmental stresses that contribute to inflammatory processes, cancer, and other degenerative diseases.”
“Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30% of affected individuals and are frequently accompanied by undesirable side effects.
Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood.
In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD.
In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.”
