Relief of nocturnal neuropathic pain with the use of cannabis in a patient with Fabry disease

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“Neuropathic pain is one of the most invalidating symptoms in patients with Fabry disease (FD), affecting their quality of life, it is linked to small fiber neuropathy and it may not respond to available disease specific treatments. We report the case of a 32 years old man with classic FD and severe neuropathic pain who, after the failure of several standard pharmaceutical approaches, was treated with medical cannabis with relief of nocturnal pain and sleep improvement.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694749/

“In conclusion: although more evidence is needed, this case report suggests that the use of medical cannabis could be considered as a pain treatment option for patient with FD, in particular for nocturnal pain relief, when other pharmacological approaches have failed.”

https://www.sciencedirect.com/science/article/pii/S2214426923000563?via%3Dihub


Exploring the Antibacterial Potential of Semisynthetic Phytocannabinoid: Tetrahydrocannabidiol (THCBD) as a Potential Antibacterial Agent against Sensitive and Resistant Strains of Staphylococcus aureus

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“Antimicrobial resistance (AMR) is one of the most challenging problems and is responsible for millions of deaths every year. We therefore urgently require new chemical entities with novel mechanisms of action. Phytocannabinoids have been adequately reported for the antimicrobial effect but not seriously pursued because of either stringent regulatory issues or poor drug-like properties. In this regard, the current work demonstrated the antibacterial potential of tetrahydrocannabidiol (THCBD, 4), a semisynthetic phytocannabinoid, against Staphylococcus aureus, the second-most widespread bug recognized by the WHO. THCBD (4) was generated from cannabidiol and subjected to extensive antibacterial screening. In in vitro studies, THCBD (4) demonstrated a potent MIC of 0.25 μg/mL against Gram-positive bacteria, S. aureus ATCC-29213. It is interesting to note that THCBD (4) has demonstrated strong effectiveness against efflux pump-overexpressing (SA-1199B, SA-K2191, SA-K2192, and Mupr-1) and multidrug-resistant (MRSA-15187) S. aureus strains. THCBD (4) has also shown a good effect in kill kinetic assays against ATCC-29213 and MRSA-15187. In the checkerboard assay, THCBD (4) has shown additive/indifference effects with several well-known clinically used antibiotics, tetracycline, mupirocin, penicillin G, and ciprofloxacin. THCBD (4) also exhibited good permeability in the artificial skin model. Most importantly, THCBD (4) has significantly reduced CFU in mice’s in vivo skin infection models and also demonstrated decent plasma exposure with 16-17% oral bioavailability. Acute dermal toxicity of THCBD (4) suggests no marked treatment-related impact on gross pathophysiology. This attractive in vitro and in vivo profile of plant-based compounds opens a new direction for new-generation antibiotics and warrants further detailed investigation.”

https://pubmed.ncbi.nlm.nih.gov/38051636/

https://pubs.acs.org/doi/10.1021/acsinfecdis.3c00154

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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

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

Cannabidiol protects the liver from α-Amanitin-induced apoptosis and oxidative stress through the regulation of Nrf2

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“α-Amanitin, the primary lethal toxin of Amanita, specifically targets the liver, causing oxidative stress, hepatocyte apoptosis, and irreversible liver damage. As little as 0.1 mg/kg of α-amanitin can be lethal for humans, and there is currently no effective antidote for α-amanitin poisoning. Cannabidiol is a non-psychoactive natural compound derived from Cannabis sativa that exhibits a wide range of anti-inflammatory, antioxidant, and anti-apoptotic effects. It may play a protective role in preventing liver damage induced by α-amanitin. To investigate the potential protective effects of cannabidiol on α-amanitin-induced hepatocyte apoptosis and oxidative stress, we established α-amanitin exposure models using C57BL/6J mice and L-02 cells in vitro. Our results showed that α-amanitin exposure led to oxidative stress, apoptosis, and DNA damage in both mouse hepatocytes and L-02 cells, resulting in the death of mice. We also found that cannabidiol upregulated the level of Nrf2 and antioxidant enzymes, alleviating apoptosis, and oxidative stress in mouse hepatocytes and L-02 cells and increasing the survival rate of mice. Our findings suggest that cannabidiol has hepatoprotective effects through the regulation of Nrf2 and antioxidant enzymes and may be a potential therapeutic drug for Amanita poisoning.”

https://pubmed.ncbi.nlm.nih.gov/37992955/

https://www.sciencedirect.com/science/article/abs/pii/S0278691523005987?via%3Dihub

Cannabis Use Linked to Enhanced Empathy

“Summary: A new study suggests regular cannabis users may have a heightened ability to understand others’ emotions. Psychological assessments coupled with brain imaging revealed that users show stronger connectivity in brain regions associated with empathy. The research, involving 136 participants, could have implications for treating social interaction deficits.

Key Facts:

  1. Regular cannabis users may have a greater empathetic understanding of others compared to non-users.
  2. Brain imaging indicates enhanced connectivity in the anterior cingulate cortex, a region related to empathy, among cannabis users.
  3. The study’s findings may inform potential treatments for social interaction deficits in various psychological conditions.”

https://neurosciencenews.com/empathy-cannabis-use-25173/

Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review

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“Cannabinoid receptors, endogenous cannabinoids (endocannabinoids), and the enzymes involved in the biosynthesis and degradation of the endocannabinoids make up the endocannabinoid system (ECS). The components of the ECS are proven to modulate a vast bulk of various physiological and pathological processes due to their abundance throughout the human body. Such discoveries have attracted the researchers’ attention and emerged as a potential therapeutical target for the treatment of various diseases.

In the present article, we reviewed the discoveries of natural compounds, herbs, herbs formula, and their therapeutic properties in various diseases and disorders by modulating the ECS. We also summarize the molecular mechanisms through which these compounds elicit their properties by interacting with the ECS based on the existing findings.

Our study provides the insight into the use of natural compounds that modulate ECS in various diseases and disorders, which in turn may facilitate future studies exploiting natural lead compounds as novel frameworks for designing more effective and safer therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/37906390/

https://link.springer.com/article/10.1007/s43440-023-00544-7

The Antioxidant and Neuroprotective Potential of Leaves and Inflorescences Extracts of Selected Hemp Varieties Obtained with scCO2

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“Cannabis sativa, a versatile plant with numerous varieties, holds promising potential for a wide range of biological activity. As raw materials for research, we chose leaves and inflorescences of hemp varieties such as Białobrzeskie, Henola, and Tygra, which are cultivated mainly for their fibers or seeds. The choice of extraction is a key step in obtaining the selected compositions of active compounds from plant material. Bearing in mind the lipophilic nature of cannabinoids, we performed supercritical carbon dioxide (scCO2) extraction at 50 °C under 2000 (a) and 6000 PSI (b). The cannabinoid contents were determined with the use of the HPLC-DAD method. The antioxidant capabilities were assessed through a series of procedures, including the DPPH, ABTS, CUPRAC, and FRAP methods. The capacity to inhibit enzymes that play a role in the progression of neurodegenerative diseases, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase was also studied. The dominant cannabinoids in the extracts were cannabidiol (CBD) and cannabidiolic acid (CBDA). The highest concentration of eight cannabinoids was detected in the Tygra inflorescences extract (b). The most notable antioxidant properties were provided by the Tygra inflorescences extract (b). Nonetheless, it was the Henola inflorescences extract (b) that demonstrated the most efficient inhibition of AChE and BChE, and tyrosinase was inhibited the most significantly by the Białobrzeskie inflorescences extract (b). Multidimensional comparative analysis enrolled all assays and revealed that the Henola inflorescences extract (b) showed the most substantial neuroprotective potential.”

https://pubmed.ncbi.nlm.nih.gov/37891906/

https://www.mdpi.com/2076-3921/12/10/1827

Cannabidiol Reduces Systemic Immune Activation in Experimental Acute Lung Injury

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“Background: The underlying pathomechanism of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the immune response to inflammation or infection within the pulmonary microcirculation. Systemic spread of pathogens, activated immune cells, and inflammatory mediators contributes significantly to mortality in patients with ARDS. 

Objective: The endogenous cannabinoid system is a major modulator of the immune response during inflammation and infection. Phytocannabinoids, such as cannabidiol (CBD), have shown promising anti-inflammatory effects in several pathologies. The overall objective of this study was to evaluate the effects of CBD on local and systemic inflammation in endotoxin-induced ALI in mice. 

Materials and Methods: ALI was induced by pulmonary endotoxin challenge. Four groups of male C57BL/6 mice were randomized in this study: control, ALI, ALI with CBD treatment, and control with CBD treatment. Analyses of local and systemic cytokine levels, lung histology, and leukocyte activation as visualized by intravital microscopy of the intestinal and pulmonary microcirculation were performed 6 h following intranasal endotoxin administration. 

Results: Pulmonary endotoxin challenge induced significant inflammation evidenced by local and systemic cytokine and chemokine release, lung histopathology, and leukocyte adhesion. Intraperitoneal CBD treatment resulted in a significant decrease in systemic inflammation as shown by reduced leukocyte adhesion in the intestinal microcirculation and reduced plasma cytokine and chemokine levels. Pulmonary chemokine levels were decreased, while pulmonary cytokine levels were unchanged. Surprisingly, the ALI score was slightly increased by CBD treatment in a manner driven by enhanced neutrophil infiltration of the alveoli. 

Conclusion: In this model of experimental ALI, CBD administration was associated with reduced systemic inflammation and heterogeneous effects on pulmonary inflammation. Future studies should explore the mechanisms involved as they relate to neutrophil infiltration and proinflammatory mediator production within the lungs.”

https://pubmed.ncbi.nlm.nih.gov/37815809/

https://www.liebertpub.com/doi/10.1089/can.2023.0039