Graphene quantum dots based on cannabis seeds for efficient wound healing in a mouse incisional wound model: Link with stress and neurobehavioral effect

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“Graphene quantum dots (GQDs) are promising biomaterials with potential applicability in several areas due to their many useful and unique features. Among different applications, GQDs are photodynamic therapy agents that generate single oxygen and improve antimicrobial activity. In the present study, and for the first time, GQD were isolated from the Cannabis sativa L. seeds to generate C-GQD as a new biomaterial for antibacterial and wound healing applications. Detailed characterization was performed using FTIR, UV-vis, Raman spectra, photoluminescence, TEM examination, HRTEM, ζ-potential, and XRD. Our results revealed in vitro and in vivo antibacterial activity of C-GQDs against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with reduced minimal inhibitory concentration (MIC) of 236µg/mL for both strains. In addition, the C-GQDs confirmed the in vitro analysis and exhibited anti-inflammatory activity by reducing the level of neutrophils in blood and skin tissue. C-GQDs act by accelerating re-epithelization and granulation tissue formation. In addition, C-GQDs restored neurobehavioral alteration induced by incisional wounds by reducing oxidative stress, decreasing cortisol levels, increasing anxiolytic-like effect, and increasing vertical locomotor activity. The wound-healing effects of C-GQDs support its role as a potential therapeutic agent for diverse skin injuries.”

https://pubmed.ncbi.nlm.nih.gov/38042382/

“In the present work, Cannabis sativa L. seeds GQDs (termed here as C-GQDs) were generated through a novel eco-friendly approach using cannabis seeds as precursor and without the addition of strong oxidants, thus avoiding the production of toxic gases.

Cannabis seeds offer an opportunity in regard to versatility, cost, and availability. They are a rich source of fiber and have significant medicinal value. They contain antibacterial cannabinoids with the potential to kill antibiotic-resistant bacteria. They also possess analgesics and anti-inflammatory effects that can be used in various biomedical applications.

More importantly, we found that C-GQDs accelerate the healing process by killing S. aureus and E. coli implicated in skin wound infection.

The C-GQDs, via their antibacterial, anti-inflammatory, anti-stress, anxiolytic-like effects showed an accelerative potential of wound closure in mice models of incisional wounds.”

https://www.sciencedirect.com/science/article/abs/pii/S0378517323010803?via%3Dihub

Cannabidiol represses miR-143 to promote cardiomyocyte proliferation and heart regeneration after myocardial infarction

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“Mammalian heart is capable to regenerate almost completely early after birth through endogenous cardiomyocyte proliferation. However, this regenerative capacity diminishes gradually with growth and is nearly lost in adulthood. Cannabidiol (CBD) is a major component of cannabis and has various biological activities to regulate oxidative stress, fibrosis, inflammation, and cell death. The present study was conducted to investigate the pharmacological effects of CBD on heart regeneration in post-MI mice. MI models in adult mice were constructed via coronary artery ligation, which were administrated with or without CBD. Our results demonstrate that systemic administration (10 mg/kg) of CBD markedly increased cardiac regenerative ability, reduced infarct size, and restored cardiac function in MI mice. Consistently, in vitro study also showed that CBD was able to promote the proliferation of neonatal cardiomyocytes. Mechanistically, the expression of miR-143-3p related to cardiomyocyte proliferation was significantly down-regulated in CBD-treated cardiomyocytes, while the overexpression of miR-143-3p inhibited cardiomyocyte mitosis and eliminated CBD-induced cardiomyocyte proliferation. Moreover, CBD enhanced the expression of Yap and Ctnnd1, which were demonstrated as the target genes of miR-143-3p. Silencing of Yap and Ctnnd1 hindered the proliferative effects of CBD. We further revealed that inhibition of the cannabinoid receptor 2 impeded the regulatory effect of CBD on miR-143-3p and its downstream target Yap/Ctnnd1, which ultimately eliminated the pro-proliferative effect of CBD on neonatal and adult cardiomyocytes. Taken together, CBD promotes cardiomyocyte proliferation and heart regeneration after MI via miR-143-3p/Yap/Ctnnd1 signaling pathway, which provides a new strategy for cardiac repair in adult myocardium.”

https://pubmed.ncbi.nlm.nih.gov/38052413/

“Cannabidiol (CBD)-an abundant component of cannabis with no psychoactive or cognitive effect has been shown to have extensive therapeutic properties including neuroprotection, anti-inflammation, anti-tumor and analgesic effects. In addition, multiple lines of evidence indicated that CBD is a potent protective agent against cardiovascular disease.”

https://www.sciencedirect.com/science/article/abs/pii/S0014299923007598?via%3Dihub

Antinociceptive action of cannabidiol on thermal sensitivity and post-operative pain in male and female rats

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“This study investigated the antinociceptive potential of cannabidiol (CBD) in male and female Wistar rats. The assessment and analysis included tail withdrawal to thermal stimulation (tail flick test) and mechanical allodynia induced by plantar incision injury (von Frey test). CBD reduced acute thermal sensitivity in uninjured animals and post-operative mechanical allodynia in males and females. In the tail flick test, CBD 30mg/kg i.p. was required to induce antinociception in males. During the proestrus phase, females did not show a statistically significant antinociceptive response to CBD treatment despite a noticeable trend. In contrast, in a separate group of rats tested during the late diestrus phase, antinociception varied with CBD dosage and time. In the post-operative pain model, CBD at 3mg/kg decreased mechanical allodynia in males. Similarly, this dose reduced allodynia in females during proestrus. However, in females during late diestrus, the lower dose of CBD (0.3mg/kg) reduced mechanical allodynia, although the latency to onset of the effect was slower (90minutes). The effectiveness of a 10-fold lower dose of CBD during the late diestrus stage in females suggests that ovarian hormones can influence the action of CBD. While CBD has potential for alleviating pain in humans, personalized dosing regimens may need to be developed to treat pain in women.”

https://pubmed.ncbi.nlm.nih.gov/38048909/

“•CBD produces antinociception in male and female rats.

•CBD was effective against acute thermal and post-operative pain in both sexes.

•Females in late diestrus were sensitive to a 10-fold lower dose of CBD than in proestrus.”

https://www.sciencedirect.com/science/article/pii/S0166432823005119?via%3Dihub


Cancer-Cachexia-Induced Human Skeletal Muscle Myotube Degeneration Is Prevented via Cannabinoid Receptor 2 Agonism In Vitro

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“Cachexia syndrome, leading to reduced skeletal muscle and fat mass, is highly prevalent in cancer patients, resulting in further negative implications for these patients. To date, there is no approved therapy for cachexia syndrome. The objective of this study was to establish an in vitro model of cancer cachexia in mature human skeletal muscle myotubes, with the intention of exploiting the cell model to assess potential cachexia therapeutics, specifically cannabinoid related drugs. Having cultured and differentiated primary human muscle myoblasts to mature myotubes, we successfully established two cancer cachexia models using conditioned media (CM) from human colon adenocarcinoma (SW480) and from non-small-cell lung carcinoma (H1299) cultured cells. The cancer-CM-induced extensive myotube degeneration, demonstrated by a significant reduction in mature myotube diameter, which progressed over the period studied. Myotube degeneration is a characteristic feature of cancer cachexia and was used in this study as an index of cachexia. Expression of cannabinoid 1 and 2 receptors (CB1R and CB2R) was confirmed in the mature human skeletal muscle myotubes. Subsequently, the effect of cannabinoid compounds on this myotube degeneration were assessed.

Tetrahydrocannabinol (THC), a partial CB1R/CB2R agonist, and JWH133, a selective CB2R agonist, proved efficacious in protecting mature human myotubes from the deleterious effects of both (SW480 and H1299) cancer cachexia conditions.

ART27.13, a full, peripherally selective CB1R/CB2R agonist, currently being trialled in cancer cachexia (IRAS ID 278450, REC 20/NE/0198), was also significantly protective against myotube degeneration in both (SW480 and H1299) cancer cachexia conditions. Furthermore, the addition of the CB2R antagonist AM630, but not the CB1R antagonist Rimonabant, abolished the protective effect of ART27.13. In short, we have established a convenient and robust in vitro model of cancer-induced human skeletal muscle cachexia. The data obtained using the model demonstrate the therapeutic potential of ART27.13 in cancer-induced cachexia prevention and provides evidence indicating that this effect is via CB2R, and not CB1R.”

https://pubmed.ncbi.nlm.nih.gov/38004445/

“Several cannabinoid drugs have emerged as potential therapeutics for various conditions.”

https://www.mdpi.com/1424-8247/16/11/1580

Cannabinoids and Their Receptors in Skin Diseases

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“The therapeutic application of cannabinoids has gained traction in recent years. Cannabinoids interact with the human endocannabinoid system in the skin. A large body of research indicates that cannabinoids could hold promise for the treatment of eczema, psoriasis, acne, pruritus, hair disorders, and skin cancer. However, most of the available data are at the preclinical stage. Comprehensive, large-scale, randomized, controlled clinical trials have not yet been fully conducted. In this article, we describe new findings in cannabinoid research and point out promising future research areas.”

https://pubmed.ncbi.nlm.nih.gov/38003712/

“In recent years, some components of cannabis, also known as marijuana, have been studied. Cannabis has been used for various purposes throughout history, including recreational, medicinal, and industrial uses. In recent years, cannabinoid components are emerging as therapeutic alternatives for patients with a variety of illnesses and conditions. In particular, their anti-inflammatory properties have piqued the interest of dermatologists [1]. Given the growing number of pre-clinical and clinical studies exploring the potential of cannabinoids to treat dermatologic conditions, we here summarize reports of cannabinoid use in dermatologic therapy.”

https://www.mdpi.com/1422-0067/24/22/16523

Efficacy and safety of medical cannabinoids in children with cerebral palsy: a systematic review

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“Introduction: The increasing popularity of cannabinoids for treating numerous neurological disorders has been reported in various countries. Although it reduces tetrahydrocannabinol psychoactivity, it helps patients tolerate higher doses and complements the anti-spasmodic effects of tetrahydrocannabinol. One of the most important potential of cannabinoids are related to its potential to help children with cerebral palsy, a contributor of lifelong disability. Therefore, this systematic review aimed to assess the efficacy and safety of medical cannabinoids in children with cerebral palsy.

Methods: This review adhered to The Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Seven databases, namely, Scopus, PubMed, EBSCO Host, ProQuest, Google Scholar, Semantic Scholar, and JSTOR, were used to identify relevant studies. Studies examining pediatric patients with cerebral palsy and reporting the efficacy and safety of medical cannabinoids through clinical trials, observational cross-sectional studies, or cohort designs were included. The outcomes of the studies included the efficacy of medical cannabinoids administered for spasticity, motor components, pain control, sleep difficulties, adverse effects, and seizure control.

Results: Of 803 identified articles, only three met the inclusion criteria for data synthesis. One study exhibited a moderate risk-of-bias. A total of 133 respondents, mainly from Europe, were investigated. Overall effectiveness and safety were considered good. However, the results are inconsistent, especially regarding spasticity treatment variables.

Conclusion: The anti-spasticity, anti-inflammatory, and anti-seizure properties of cannabinoids might be beneficial for patients with cerebral palsy, although their effectiveness has not been widely studied. Further studies with larger sample sizes and various ethnicities are warranted.”

https://pubmed.ncbi.nlm.nih.gov/37991091/

https://journal.einstein.br/article/efficacy-and-safety-of-medical-cannabinoids-in-children-with-cerebral-palsy-a-systematic-review/

Cannabis and Endometriosis: The Roles of the Gut Microbiota and the Endocannabinoid System

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“Endometriosis, a chronic condition affecting around 10-14% of women, is challenging to manage, due to its complex pathogenesis and limited treatment options. Research has suggested a potential role of the gut microbiota and the endocannabinoid system in the development and progression of endometriosis. This narrative review aims to explore the role of, and any potential interactions between, the endocannabinoid system (ECS) and the gut microbiota in endometriosis. This review found that both the ECS and microbiota influence endometriosis, with the former regulating inflammation and pain perception and the latter influencing immune responses and hormonal balance. There is evidence that a dysregulation of the endocannabinoid system and the gut microbiota influence endometriosis symptoms and progression via changes in CB1 receptor expression and increased circulating levels of endocannabinoids. Microbial imbalances in the gut, such as increases in Prevotella, have been directly correlated to increased bloating, a common endometriosis symptom, while increases in E. coli have supported the bacterial contamination hypothesis as a potential pathway for endometriosis pathogenesis. These microbial imbalances have been correlated with increases in inflammatory markers such as TNF-α and IL-6, both often raised in those with endometriosis. Protective effects of the ECS on the gut were observed by increases in endocannabinoids, including 2-AG, resulting in decreased inflammation and improved gut permeability. Given these findings, both the ECS and the gut microbiota may be targets for therapeutic interventions for endometriosis; however, clinical studies are required to determine effectiveness.”

https://pubmed.ncbi.nlm.nih.gov/38002684/

https://www.mdpi.com/2077-0383/12/22/7071

Terpenes in Cannabis sativa Inhibit Capsaicin Responses in Rat DRG Neurons via Na+/K+ ATPase Activation

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“Terpenes in Cannabis sativa exert analgesic effects, but the mechanisms are uncertain. We examined the effects of 10 terpenes on capsaicin responses in an established model of neuronal hypersensitivity. Adult rat DRG neurons cultured with neurotrophic factors NGF and GDNF were loaded with Fura2AM for calcium imaging, and treated with individual terpenes or vehicle for 5 min, followed by 1 µMol capsaicin. In vehicle treated control experiments, capsaicin elicited immediate and sustained calcium influx. Most neurons treated with terpenes responded to capsaicin after 6-8 min. Few neurons showed immediate capsaicin responses that were transient or normal. The delayed responses were found to be due to calcium released from the endoplasmic reticulum, as they were maintained in calcium/magnesium free media, but not after thapsigargin pre-treatment. Terpene inhibition of calcium influx was reversed after washout of medium, in the absence of terpenes, and in the presence of the Na+/K+ ATPase inhibitor ouabain, but not CB1 or CB2 receptor antagonists. Thus, terpenes inhibit capsaicin evoked calcium influx by Na+/K+ ATPase activation. Immunofluorescence showed TRPV1 co-expression with α1β1 Na+/K+ ATPase in most neurons while others were either TRPV1 or α1β1 Na+/K+ ATPase positive.”

https://pubmed.ncbi.nlm.nih.gov/38003528/

“The neuromodulatory effects of cannabinoids have been recognized for millenia in traditional medicine, including for pain relief. Following the opioid crisis, attention has been focussed on developing alternatives including cannabinoid-based pain therapies, as chronic pain remains an unmet need. The best known of the phytocannabinoids is Δ9tetrahydrocannabinol (THC), the only known psychoactive component, along with many other cannabinoids with potential therapeutic benefits, such as cannabidiol (CBD), and cannabigerol (CBG) [2]. Amongst the several hundred components in Cannabis sativa are terpenes, which are produced in small and varying amounts in different cultivars of C. sativa, leading to potential variation in their effects [3]. Some of these, including limonene, phytol, borneol, terpineol, and caryophyllene, provide pain relief via calcium channel inhibition [4]. Similarly, antinociceptive and anti-tumour effects of α-phellandrene were reported, although the mechanisms were unknown. Terpenes as a class of compounds are generally described as safe by the FDA, with low toxicity that extends their efficacy to a variety of indications including chronic pain and anxiety.”

https://www.mdpi.com/1422-0067/24/22/16340

An Emerging Strategy for Neuroinflammation Treatment: Combined Cannabidiol and Angiotensin Receptor Blockers Treatments Effectively Inhibit Glial Nitric Oxide Release

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“Cannabidiol (CBD), the major non-psychoactive phytocannabinoid found in cannabis, has anti-neuroinflammatory properties.

Despite the increasing use of CBD, little is known about its effect in combination with other substances. Combination therapy has been gaining attention recently, aiming to produce more efficient effects. Angiotensin II activates the angiotensin 1 receptor and regulates neuroinflammation and cognition. Angiotensin receptor 1 blockers (ARBs) were shown to be neuroprotective and prevent cognitive decline. The present study aimed to elucidate the combined role of CBD and ARBs in the modulation of lipopolysaccharide (LPS)-induced glial inflammation. While LPS significantly enhanced nitric oxide synthesis vs. the control, telmisartan and CBD, when administered alone, attenuated this effect by 60% and 36%, respectively. Exposure of LPS-stimulated cells to both compounds resulted in the 95% inhibition of glial nitric oxide release (additive effect). A synergistic inhibitory effect on nitric oxide release was observed when cells were co-treated with losartan (5 μM) and CBD (5 μM) (by 80%) compared to exposure to each compound alone (by 22% and 26%, respectively). Telmisartan and CBD given alone increased TNFα levels by 60% and 40%, respectively. CBD and telmisartan, when given together, attenuated the LPS-induced increase in TNFα levels without statistical significance. LPS-induced IL-17 release was attenuated by CBD with or without telmisartan (by 75%) or telmisartan alone (by 60%). LPS-induced Interferon-γ release was attenuated by 80% when telmisartan was administered in the absence or presence of CBD. Anti-inflammatory effects were recorded when CBD was combined with the known anti-inflammatory agent dimethyl fumarate (DMF)/monomethyl fumarate (MMF). A synergistic inhibitory effect of CBD and MMF on glial release of nitric oxide (by 77%) was observed compared to cells exposed to MMF (by 35%) or CBD (by 12%) alone. Overall, this study highlights the potential of new combinations of CBD (5 μM) with losartan (5 μM) or MMF (1 μM) to synergistically attenuate glial NO synthesis. Additive effects on NO production were observed when telmisartan (5 μM) and CBD (5 μM) were administered together to glial cells.”

https://pubmed.ncbi.nlm.nih.gov/38003444/

https://www.mdpi.com/1422-0067/24/22/16254

Oil Extraction from Hemp Plant as a Potential Source of Cannabidiol for Healthy Protein Foods

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“In recent years, the increasing demand for alternative foods has shifted research toward new sources enriched with nutraceutical molecules. It is well known that many diseases are caused by oxidative stress; thus, the supplementation of antioxidants has been proposed to reduce it. Cannabis sativa L. is an interesting species that could provide an alternative source of antioxidants. This work aimed to investigate the possibility of optimizing the yield of cannabidiol (CBD) and recovering it from residual biomass (stalks), valorizing the residual biomass, and using this for protein bar preparation. Different extraction methods were used, and High-Pressure Liquid Chromatography (HPLC) analysis was used to analyze the extracts. Antioxidant power was investigated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. The best results in terms of CBD yield were obtained via dynamic maceration after decarboxylation with a quantity of 26.7 ± 2 mgCBD/graw material from inflorescences. The extract also shows good antioxidant power with an IC50 value of 38.1 ± 1.1 µg/mL measured using the DPPH assay. The CBD extract was added to the hemp oil to obtain dough for protein bars. The doughs were studied by taking rheological and technological measurements, and it was found that the protein bars could provide an excellent means for the consumption of products enriched with antioxidants because their CBD anti-inflammatory activity is preserved after cooking.”

https://pubmed.ncbi.nlm.nih.gov/38001803/

https://www.mdpi.com/2076-3921/12/11/1950