“The present study investigates the effects of cannabidiol (CBD), the major non-psychoactive compound of Cannabis sativa L. extracts, on ferroptotic cell death in human articular chondrocytes.
Exposure to known ferroptosis inducers RSL3, erastin and its analogue IKE, FINO2 and FIN56 led to a varying extent of reduced cell viability in two chondrocyte cell lines (in C-28/I2, T/C-28/A2) and primary chondrocytes, suggesting different sensitivity and defence mechanisms towards the respective substances. The cytotoxic effects were aggravated by additional exposure to iron and inhibited by the specific ferroptosis inhibitor ferrostatin-1 (Fer-1), proving the occurrence of ferroptosis.
Strikingly, co-treatment of ferroptosis inducers with CBD clearly restored cell viability in a dose-dependent manner (10 nM to 1 μM CBD) in both cell lines and primary chondrocytes. Moreover, CBD restored the activity of GPX4, a major anti-oxidative enzyme, to varying degrees when combined with IKE or RSL3. Increasing evidence has emerged for an important role of iron dyshomeostasis and ferroptosis in the onset and progression of various orthopaedic diseases, including osteoarthritis.
Therefore, the here demonstrated and previously unreported cytoprotective and anti-oxidative effects of CBD in the context of ferroptosis have highly promising therapeutic implications.”
“Objective: Cannabis sativa L. is aware of a rich source of bioactive substances with various structures that exhibit pharmacological activity in the central nervous system, cardiovascular, cerebrovascular, respiratory, reproductive, and gastrointestinal systems.
Materials and methods: In this study, cannabis sugar leaves were soaked in 99% ethanol, followed by evaporation. The antibacterial effect of the cannabis sugar leaf extract was then evaluated using the disc diffusion method. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using broth dilution.
Results: The results of this study indicated that the cannabis sugar leaf extract inhibited Bacillus cereus, Vibrio cholerae, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis when compared to tetracycline, but it did not inhibit Pseudomonasaeruginosa. The MIC and MBC of the cannabis sugar leaves extract against B. cereus, V. cholerae, E. coli, S. aureus, and S. epidermidis were 0.977, 1.953, 31.25, 62.5, 125, 250, 250, 500, 250, and 500 mg/ml, respectively. The bioactive compounds in cannabis sugar leaf extract were identified using high-performance liquid chromatography.
Conclusion: The results indicated that the major bioactive compounds were Δ-9- tetrahydrocannabinol (THC) and cannabidiol (CBD). While minor bioactive compounds included gallic acid and tannic acid. These results support the benefits of cannabis sugar leaf extract, which has been used for its pharmacological properties and may be useful as an alternative antimicrobial agent in medicine.”
“The endocannabinoid system (eCB) is a complex signaling network discovered in mammals during the 1980s-1990s.
It conventionally revolves around two arachidonic acid-derived mediators, N-arachidonoyl-ethanolamine (anandamide) and 2-arachidonoyl-glycerol; their main receptors, the cannabinoid receptors of type 1 (CB1) and type 2 (CB2), and the transient receptor potential vanilloid-1 channels; and the enzymes responsible for their biosynthesis and degradation. However, drawing on these discoveries, numerous eCB-like signaling lipids beyond the classical eCBs, have been unveiled, together with their receptors and metabolic enzymes, thus forming a more complex signaling network known as the endocannabinoidome (eCBome).
This review explores the physiology, pharmacological complexity, and molecular targets of the mammalian eCBome, highlighting its versatility and redundancy in the context of global health. Emerging mediators, metabolic pathways and mechanisms, receptors, and their implications in human physiology and pathology are described, particularly concerning metabolic disorders, pain, inflammation, neurodegenerative diseases, and cancer.
The importance of other “eCBomes” in nonmammalian forms of life that constitute the external and internal environments of mammals is also discussed for the first time in this context. The overarching objective of this article is to gain insights into the potential of eCBome-based therapeutic strategies aimed at enhancing both human and environmental well-being.
SIGNIFICANCE STATEMENT: Lipid-based signaling molecules are ubiquitous in nature, yet their study remains challenging due to intricate regulatory mechanisms. Among lipid signaling pathways, the endocannabinoid (eCB) system and its extended version, the endocannabinoidome (eCBome), are particularly remarkable. Comprising hundreds of mediators, and dozens of receptors and metabolic enzymes, the eCBome regulates critical physiological processes not only in mammals but also across diverse organisms, including plants, fungi, and bacteria. This article examines the evolutionary and functional diversity of eCBomes and highlights their untapped potential as multikingdom therapeutic targets to address pressing challenges in global health.”
“Monocytes are innate immune cells that release inflammatory factors upon detection of infectious and injurious stimuli. CD16+ monocytes, a subset of the total monocyte population, are associated with acute and chronic inflammation in human immunodeficiency virus-associated neurocognitive disorder and rheumatoid arthritis. Given the role monocytes play in regulating the host immune response, this investigation explored the effects of cannabinoids on the monocyte secretome for potential therapeutic applications.
Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are major cannabis-derived compounds established to have immune-modulating properties. Despite a rise in medical cannabis use, the specific mechanism by which THC and CBD modulate the inflammatory response, including by human monocytes remains poorly understood.
We hypothesized that THC and CBD suppress toll-like receptor (TLR) 7- or TLR8-induced inflammatory profiles by CD16+ and CD16– monocytes, specifically interleukin (IL) 1β maturation. Cannabinoid receptor 2 selective agonist, JWH-015, was used to deduce whether cannabinoid receptor 2 signaling alone can mimic immune-modulating properties of THC. Primary human CD16+ and CD16– monocytes were pretreated with THC, CBD, or JWH-015 and then activated through TLR7 or TLR8. Activated monocytes mainly produced IL-1β, tumor necrosis factor-⍺, and IL-6.
We show that THC and CBD, but not JWH-015, exert anti-inflammatory effects on primary human monocyte apoptosis-associated speck-like protein-incorporating inflammasome formation and subsequent caspase-1 activity, contributing to suppressed IL-1β production. In addition, mRNA expression of IL1B, CASP1, NLRP3, and PYCARD were unaffected by THC. Minimal THC effects were observed on TLR8-mediated AIM2 mRNA expression.
Collectively, results from these studies suggest THC and CBD may be useful in mitigating IL-1β-mediated acute or chronic inflammation.
SIGNIFICANCE STATEMENT: This current investigation aimed to understand the role of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in mediating virally activated CD16+ monocyte inflammatory cytokine production. Further, the results indicated that THC and CBD selectively suppress monocyte interleukin 1β production, though THC is more efficacious, through its maturation, as evidenced by suppressed caspase-1 activity and apoptosis-associated speck-like protein-incorporating inflammasome formation.
This work provides evidence to support that THC, and to an extent CBD, exert anti-inflammatory effects that could be useful in mitigating monocyte interleukin 1β-mediated chronic inflammation.”
“Background: Eicosanoids-lipid mediators derived from polyunsaturated fatty acids such as arachidonic acid-have a notable role in inflammatory signaling. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have been shown in preclinical studies to modulate inflammatory pathways the modulating the enzymes that generate eicosanoids, namely lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450).
Methods: This present study aimed to investigate how CBD and THC effect plasma levels of eicosanoids generated through LOX, COX, and cytochrome P450 (CYP450) pathways. Using plasma sample data from multiple clinical studies, we tested the hypothesis that high-CBD cannabis use would increase eicosanoid levels compared with high-THC cannabis.
Results: Following cannabis use, high-CBD cannabis led to a rise in plasma eicosanoids, particularly lipoxins, while high-THC cannabis did not.
Conclusions: CBD promoted anti-inflammatory eicosanoid production via the 15-LOX pathway, therefore supporting the potential role of CBD as a therapeutic candidate for inflammatory diseases.”
“Purpose: Although medical cannabis (MC) has been shown to relieve cancer- and treatment-related symptoms, there is increasing misinformation regarding its antitumor efficacy. We aimed to identify opportunities for oncologists to communicate evidence-based guidance to patients regarding its use.
Methods and materials: Patients with cancer seen in radiation oncology clinic between June 2022 and July 2023 were surveyed with a questionnaire regarding their perceptions and information sources of MC. Associations between survey responses and demographic and disease variables were evaluated. Qualitative thematic analysis was performed on narrative responses in search of common themes.
Results: Eighty-four patients (84% completion rate) were included in the analysis. Most (83.3%) strongly agreed or agreed that MC can provide symptom relief, whereas a subset of patients (15.5%) strongly agreed or agreed that MC can cure cancer. This latter subcohort was significantly more likely to identify as Hispanic/Latino (38.5% vs 9.9%, P = .009) and less likely to be up to date on COVID-19 vaccinations (30.8% vs 8.5%, P = 0.044). Identifying as Hispanic/Latino remained significantly associated with strongly agreeing or agreeing that MC can cure cancer on bivariate analysis (odds ratio, 6.528; 95% CI, 1.477-28.715; P = .012). Education level, other sociodemographic characteristics, and sources for information about MC were not significantly different between these patients. Thematic analysis revealed that patients hoped to learn more about MC from their oncologists but perceived them to be unknowledgeable on the subject.
Conclusions: Although most patients consider MC to be a valuable addition to conventional therapies for managing refractory symptoms, a subset believed it had potential as an anticancer therapy. Many patients rely on unregulated sources, highlighting the need for providers to address misinformation, bridge knowledge gaps, and clarify its use.”
“Most patients (83.3%) strongly agreed or agreed that MC can provide symptom relief for cancer and treatment-related symptoms, whereas 15.5% strongly agreed or agreed that MC can cure cancer.”
“Iron oxide nanoparticles (IONPs) have emerged as the most widely synthesized metal nanoparticles in sustainable chemistry due to their unique magnetic properties, excellent biocompatibility, biodegradability, and non-toxicity.
In this study, IONPs are successfully synthesized via a rapid, sustainable, and environmentally friendly green synthesis approach using Cannabis sativa L. leaf extract. X-ray diffraction analysis determined that the synthesized NPs had an average particle size of 18.8 nm, while transmission electron microscopy images reveal a spherical morphology with sizes ranging from 12 to 21 nm.
Fourier-transform infrared spectroscopy analysis confirmed the presence of cannabinoids, terpenoids, and flavonoids, which are believed to play a crucial role in the formation and stabilization of IONPs. Its photocatalytic potential is demonstrated through the degradation of bromophenol blue dye.
Additionally, the NPs exhibited significant antibacterial and antifungal activity against various microbial species, along with promising anticancer effects on cancer cell lines.
In conclusion, this study provides a promising foundation for advancing the large-scale, commercial production of IONPs through green synthesis methods. By offering an eco-friendly and efficient alternative to conventional nanoparticle synthesis, the findings contribute significantly to the growing body of research in sustainable nanotechnology.”
“In this study, IONPs were successfully synthesized via a single-step green approach using C. sativa leaf extract as the sole reducing and stabilizing agent, eliminating the need for secondary chemicals. Collectively, these findings underscore the potential of eco-friendly IONPs for biomedical and environmental applications, aligning with sustainable nanotechnology paradigms.”
“Inflammation is the organism’s protective mechanism to restore cellular and tissue homeostasis. Cannabidiol has been reported for its ability to bind to diverse receptors related to or not related to the endocannabinoid system, with good safety being one of the most promising phytocannabinoids for therapeutical purposes. CBD has shown in vitro and in vivo ability to significantly reduce the production of cytokines and other inflammatory mediators, with an unclear mechanism of action.
Herein, we report the design and synthesis of a novel series of eight terpene N-acylaryl hydrazone analogues and their pharmacological evaluation for potential antioxidant, antinociceptive, and anti-inflammatory properties.
Our results led to the identification of compounds 5a (PQM-242), with significant peripheral and central antinociceptive effects, 5b (PQM-243), and 5g (PQM-248) with antinociceptive activities probably related to the ability of modulation of TRPV1 receptors, and 5c (PQM-244) that seems to have the most promising peripheral antinociceptive profile, showing significant effects on both neurogenic and inflammatory phases of formalin-induced licking test, coupled to potential antioxidant activity.
Overall, our experimental data suggest that the new CBD-based architecture is capable of ensuring peripheral and central antinociceptive effects by different modes of action, with no in vivo toxicity and adequate predicted ADME properties.”
“There is an urgent need for alternative antimicrobial therapies in veterinary small animal dermatology due to the limited therapeutic options available for treatment of infections caused by multidrug-resistant bacteria.
This study aimed to evaluate the potential of hemp (Cannabis sativa L.) seed oil for topical treatment of localized infections of the skin, such as otitis externa.
Antimicrobial activity was determined by broth microdilution using a strain collection of bacterial pathogens associated with skin infections, including Staphylococcus pseudintermedius (n=120), Staphylococcus aureus (n=48), and Pseudomonas aeruginosa (n=26). Checkerboard dilution tests were used to assess the interaction of hemp seed oil with two antimicrobials used for management of otitis externa, gentamicin and enrofloxacin, while in vitro cytotoxicity was evaluated by the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay on mouse fibroblast cell line L929. Minimum inhibitory concentrations (MICs) in staphylococci (0.025-0.2% v/v) were markedly lower than in P. aeruginosa (>0.4% v/v). Within S. pseudintermedius, methicillin-resistant strains displayed lower susceptibility compared to susceptible strains.
Hemp seed oil showed synergy with gentamicin (Fractional Inhibitory Concentration Index < 0.5), reducing the MIC of gentamicin-resistant S. pseudintermedius strains (≥16µg/ml) below the clinical susceptibility breakpoint (≤4µg/ml). No changes in cell viability were observed at concentrations below 2% v/v.
These findings suggest that hemp seed oil could be an effective and safe alternative or adjuvant to conventional antimicrobials for managing otitis externa and other skin focal infections caused by staphylococci, including methicillin-resistant strains.”
“The findings suggest that hemp seed oil could serve as an effective and safe alternative or adjunct to conventional antimicrobial treatments for localized skin infections, including otitis externa caused by staphylococci, even those resistant to methicillin;”
“Hemp (Cannabis sativa L.) is a versatile crop that can be processed to obtain different products with multiple applications. Its seeds are a well-documented ancient source of proteins, fibers and fats, all of which possess high nutritional value. Additionally, metabolites such as flavones and phenols are present in the seeds, contributing to their antioxidant properties.
Due to hemp seeds’ distinctive nutritional profile, the interest in exploring the potential use in food and nutraceuticals is growing, and they can be considered an interesting and promising alternative resource for human and animal feeding. Omics studies on hemp seeds and their by-products are also being developed, and they contribute to improving our knowledge about the genome, transcriptome, proteome, metabolome/lipidome, and ionome of these sustainable food resources.
This review illustrates the main nutrients and bioactive compounds of hemp seeds and explores the most relevant omics techniques and investigations related to them. It also addresses the various products derived from processing the whole seed, such as oil, dehulled seeds, hulls, flour, cakes, meals, and proteins. Moreover, this work discusses research aimed at elucidating the molecular mechanisms underlying their protein, lipid, fiber, and metabolic profile. The advantages of using omics and multi-omics approaches to highlight the nutritional values of hemp seed by-products are also discussed.
In our opinion, this work represents an excellent starting point for researchers interested in studying hemp seeds as source of nutrients and bioactive compounds from a multi-level molecular perspective.”
“By advancing the understanding and utilization of hemp seeds and their by-products in food, feed, and medical applications, we hope to contribute to positioning hemp as a sustainable and valuable resource for the future.”
