Cas-9 signaling pathway

Posted on February 7, 2025 by David

“Purpose: This study aimed to investigate the hypothesis that cannabidiol (CBD), with known anti-inflammatory and anti-apoptotic effects, would reduce the severity of acute lung injury in pulmonary contusion following blunt chest trauma.

Methods: Forty male Wistar Albino rats were randomly divided into four groups, each consisting of 10 rats: Sham, Trauma, Trauma + CBD, and CBD. The rats were treated with a single dose of 5 mg/kg CBD intraperitoneally 30 min before trauma. Then, the trauma were exposed to a weight of 200 g and a height of 1 m. After sacrifice, the lung tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analyses.

Results: Pulmonary injury of trauma group led to increases in tumor necrosis factor α, caspase-3, caspase-9, Bcl-2-associated X protein expressions, total oxidant status, oxidative stress index levels, and decreases in B-cell lymphoma expression and total antioxidant levels. Additionally, inflammatory cell infiltration, damage-related emphysema, pronounced hyperemia, and increased septal tissue thickness were observed histopathologically. CBD treatment ameliorated all these findings.

Conclusion: CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. More detailed studies investigating other important intracellular pathways are needed.”

https://pubmed.ncbi.nlm.nih.gov/39918746/

“In conclusion, it has been observed that CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. In addition, the effects of a single dose of CBD were examined in this study, and more detailed molecular studies are needed in which longer-term use or higher doses are preferred, in addition to this study, which highlights the acute effects of CBD. The ability to perform analyses at the gene level at the protein level via the western blot method will increase the effectiveness of the study.”

https://link.springer.com/article/10.1007/s00068-025-02767-0

Advances in cannabinoid receptors pharmacology: from receptor structural insights to ligand discovery

Posted on February 6, 2025 by David

“The medicinal and recreational uses of Cannabis sativa have been recognized for thousands of years.

Today, cannabis-derived medicines are used to treat a variety of conditions, including chronic pain, epilepsy, multiple sclerosis, and chemotherapy-induced nausea. However, cannabis use disorder (CUD) has become the third most prevalent substance use disorder globally.

Cannabinoid receptors are the primary targets that mediate the effects of cannabis and its analogs. Despite their importance, the mechanisms of modulation and the full therapeutic potential of cannabinoid receptors remain unclear, hindering the development of the next generation of cannabinoid-based drugs.

This review summarizes the discovery and medicinal potential of phytocannabinoids and explores the distribution, signaling pathways, and functional roles of cannabinoid receptors. It also discusses classical cannabinoid drugs, as well as agonists, antagonists, and inverse agonists, which serve as key therapeutic agents.

Recent advancements in the development of allosteric drugs are highlighted, with a focus on positive and negative allosteric modulators (PAMs and NAMs) that target CB1 and CB2 receptors. The identification of multiple allosteric sites on the CB1 receptor and the structural basis for allosteric modulation are emphasized, along with the structure-based discovery of ago-BAMs for CB1.

This review concludes by examining the future potential of allosteric modulators in cannabinoid drug development, noting that ongoing progress in cannabinoid-derived drugs continues to open new avenues for therapeutic use and paves the way for future research into their full medicinal potential.”

https://pubmed.ncbi.nlm.nih.gov/39910211/

https://www.nature.com/articles/s41401-024-01472-9

The effects of recreational cannabis laws on alcohol and tobacco use among US adults, 2012 to 2022

Posted on February 6, 2025 by David

“Introduction: Many states have legalized cannabis for medicinal and recreational purposes in the past decade. However, it is unclear how recreational cannabis laws (RCLs) may affect alcohol and tobacco use among adults.

Methods: This is a cross-sectional study of 4.8 million adults from the 2012-2022 Behavioral Risk Factor Surveillance System. A difference-in-differences approach was used to examine the impact of RCLs on the use of alcohol and tobacco, adjusting for individual-level characteristics and time-varying state-level factors. The analyses were performed in 2024.

Results: Three alcohol use outcomes (current drinking, binge drinking, and heavy drinking) and two tobacco use outcomes (current tobacco use and smokeless tobacco use) were examined. Considering passage of cannabis laws as RCL implementation,

RCLs were not associated with any alcohol or tobacco use outcomes in the fully adjusted model. However, considering operational dispensary as RCL implementation, RCLs were associated with a decrease of 0.95 percentage point (95% CI, 1.80 to 0.09) in current drinking and a decrease of 0.48 percentage point (95% CI, 0.85 to 0.10) in current cigarette use.

Subgroup analysis showed that RCLs were associated with reductions in current drinking, binge drinking, and current cigarette use in multiple groups. However, RCLs were associated with increases in current smokeless tobacco use for some groups.

Conclusions: The findings suggest that while the overall effects of RCLs on the use of alcohol and tobacco may be limited, there are heterogeneous associations of RCLs with drinking and smoking by age, sex, race and ethnicity, education, and income.”

https://pubmed.ncbi.nlm.nih.gov/39909135/

https://www.ajpmonline.org/article/S0749-3797(25)00038-8/abstract

Cannabidiol-Induced Autophagy Ameliorates Tau Protein Clearance

Posted on February 4, 2025 by David

“Tau is a neuronal protein that confers stability to microtubules; however, its hyperphosphorylation and accumulation can lead to an impairment of protein degradation pathways, such as autophagy. Autophagy is a lysosomal catabolic process responsible for degrading cytosolic components, being essential for cellular homeostasis and survival.

In this context, autophagy modulation has been postulated as a possible therapeutic target for the treatment of neurodegenerative diseases.

Studies point to the modulatory and neuroprotective role of the cannabinoid system in neurodegenerative models and here it was investigated the effects of cannabidiol (CBD) on autophagy in a human neuroblastoma strain (SH-SY5Y) that overexpresses the EGFP-Tau WT (Wild Type) protein in an inducible Tet-On system way.

The results demonstrated that CBD (100 nM and 10 µM) decreased the expression of AT8 and total tau proteins, activating autophagy, evidenced by increased expression of light chain 3-II (LC3-II) protein and formation of autophagosomes.

Furthermore, the cannabinoid compounds CBD, ACEA (CB1 agonist) and GW-405,833 (CB2 agonist) decreased the fluorescence intensity of EGFP-Tau WT; and when chloroquine, an autophagic blocker, was used, there was a reversal in the fluorescence intensity of EGFP-Tau WT with CBD (1 and 10 µM) and GW-405,833 (2 µM), demonstrating the possible participation of autophagy in these groups.

Thus, it was possible to conclude that CBD induced autophagy in EGFP-Tau WT cells which increased tau degradation, showing its possible neuroprotective role. Hence, this study may contribute to a better understanding of how cannabinoids can modulate autophagy and present a potential therapeutic target in a neurodegeneration model.”

https://pubmed.ncbi.nlm.nih.gov/39900844/

“CBD induces autophagy promoting tau clearance in an in vitro model of tauopathy. Moreover, CBD, ACEA and GW-405,833 decreased tau expression, which was reversed by chloroquine indicating that autophagy participates in tau clearance.

Our results support the relevance of cannabinoid compounds in the autophagic process involved in the degradation of accumulated tau, which has been associated with several neuropathies. Therefore, autophagy is a potential therapeutic target of cannabinoids in neurodegenerative diseases.”

https://link.springer.com/article/10.1007/s12640-025-00729-3

Physiochemical properties of hemp extract (Cannabis sativa L) inflorescences grown in Northern Alabama

Posted on February 3, 2025 by David

“Medicinal plants are an excellent source of bioactive components and are gaining significant attention for food protection due to their bioactive properties.

In this context, hemp (Cannabis sp.) is being explored for such applications because of its well-known antibacterial and antioxidant activities. However, the bioactive efficacy of cultivars currently grown in Northern Alabama has not been widely studied. Therefore, the purpose of this study was to evaluate the physicochemical properties of two hemp cultivars (Hemp 5 and Hemp 17).

Hemp inflorescences grown at the Winfred Thomas Agricultural Research Station were used in this study. The antioxidant activity and content of the extracts were determined by ferric reducing antioxidant power, radical scavenging activity, total phenolic content, and total flavonoid content. Antibacterial activity against cocktails of Listeria monocytogenes (LM) and Salmonella enterica (SE) was evaluated by optical density and disc diffusion. All treatments were analyzed in triplicate, and analysis of variance was conducted with statistical significance based on p ≤ 0.05.

Results indicated that cultivars and defatting significantly affected (p ≤ 0.05) the antioxidant properties, with Hemp 17 DF (defatted) having the highest RSA (70.51 ± 4.24%) compared to the positive control of ascorbic acid (83.81 ± 5.85%). Antibacterial results based on optical density indicated that hemp extracts had a significantly (p ≤ 0.05) lower optical density compared to the negative controls (LM and SE).

These findings suggest that Northern Alabama hemp cultivars can potentially be utilized to enhance food safety and quality.

PRACTICAL APPLICATION: Northern Alabama cultivars of hemp extract can be utilized for the enhancement of the safety and quality application due to inherent antioxidant and antimicrobial properties.”

https://pubmed.ncbi.nlm.nih.gov/39898995/

https://ift.onlinelibrary.wiley.com/doi/10.1111/1750-3841.17642

In vitro characterization the antioxidant and antibacterial properties of hemp (Cannabis sativa spp.) varieties cultivated in Northern Alabama

Posted on February 2, 2025 by David

“Plants, especially those recognized for their medicinal properties, are an excellent source of bioactive components and are attracting considerable interest in the food industry due to their natural bioactivity.

In this context, hemp species (Cannabis sativa spp.) were investigated for such applications because of their well-documented antibacterial and antioxidant activities. However, the bioactive efficacy of varieties being introduced in Northern Alabama and their implications for food safety have not been studied.

The purpose of this study was to evaluate the antibacterial and antioxidative potential of four hemp varieties grown at the Alabama A&M University, Winfred Thomas Agricultural Research Station in Northern Alabama using three different extraction solvents (deionized water, acetone, and ethanol).

Antioxidant potential was evaluated by DPPH free radical scavenging activity (2, 2-diphenyl-1- picrylhydrazyl), Total phenolic and flavonoid contents. Antibacterial activity against cocktails of enteric pathogens, including Listeria monocytogenese, E. coli O157:H7, and Salmonella enterica was evaluated for optical density using a BioScreen-C microtiter. Also, the disc diffusion extraction yield was evaluated to determine the best extraction solvent. Data were expressed as mean ± standard error (n = 3) and ANOVA (P ≤ 0.05).

The ethanolic extracts exhibited the the highest extraction yield at 25.29 ± 0.70% (RE), while the antioxidant result demonstrated that the ethanolic extracts had the highest DPPH free radical scavenging activity at 64.03 ± 0.26% (RE).

The results of the antibacterial studies showed that ethanolic hemp extracts exhibited significantly higher growth inhibition against all foodborne pathogens > 70% (p ≤ 0.05).

The results show that the ethanolic extracts has significant extraction yield and bioactivity, highlighting ethanolic extract utilization in future antimicrobial nanofiber application.”

https://pubmed.ncbi.nlm.nih.gov/39891281/

“Hemp (Cannabis sativa). Cannabis sativa has been used for thousands of years to prevent disease in humans.”

“In various reports, hemp has been shown to contain phytochemical compounds (such as phenolics, flavonoids, and terpenophenolics) that effectively inhibit the growth of pathogenic bacteria and scavenge free radicals.

Hemp has been used in traditional medicine as a therapeutic agent with antibacterial, anti-inflammatory, and chemopreventive properties that can cure many ailments.

The ability of the hemp ethanolic extracts to scavenge the DPPH free radical indicates that they may have antioxidant properties. The inhibition of EC, SE, and LM in disc diffusion and growth inhibition assays by ethanolic hemp extracts suggests growth inhibitory effects of the extract, and pinpoints ethanol as the most effective extraction solvent for maceration extraction of northern Alabama varieties.

The obtained results support the idea that hemp grown in northern Alabama can be used as a plant-based natural preservative because of its antibacterial and antioxidant potential in food preservation. Future research is required to study quantitative antibacterial and antioxidant activities, mechanisms of antibacterial action, phytochemical profiles through analytical chromatography, and applications of hemp ethanol extract in nanotechnology.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00258-y

Retinal pharmacodynamic and pharmacokinetics profile of cannabidiol in an in vivo model of retinal excitotoxicity

Posted on February 2, 2025 by David

“Cannabidiol (CBD) is one of the principal constituents of Cannabis Sativa with no psychoactive properties. CBD is a promising neuroprotective compound bearing anti-inflammatory and antioxidant properties. However, considering its low solubility, CBD delivery to the retina represents an unresolved issue.

The first aim was to investigate the potential neuroprotective effects of CBD in an in vivo model of retinal excitotoxicity induced by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA).

Rats underwent intravitreal co-injection of AMPA (42 nmol) and CBD (10^-4 M). The neuroprotective effect of CBD was investigated with histology and immunohistochemical evaluation of inflammatory and oxidative stress biomarkers.

CBD reversed the AMPA-induced total retinal, inner nuclear layer and inner plexiform layer shrinkage and loss of amacrine cells. Moreover, CBD decreased the AMPA induced number of cleaved caspase-3, Iba-1 and nitrotyrosine (NT) positive cells.

Based on this evidence, we developed a nanotechnological formulation of CBD to overcome critical issues related to its eye delivery. Particularly, nanostructured lipid carriers (NLC) loaded with CBD were prepared, optimized and characterized.

Due to the optimal physicochemical characteristics, CBD-NLC3 has been selected and the in vitro release profile has been investigated. Additionally, CBD-NLC3 was topically administered to rats, and retinal CBD levels were determined. CBD-NLC3 formulation, after a single topical administration, efficiently delivered CBD in the retina (C_max= 98 ± 25.9 ng/mg; T_max = 60 minutes), showing a high translational value.

In conclusion, these findings showed a good PD/PK profile of CBD warranting further pre-clinical and clinical evaluation of the new formulation for the treatment of retinal degenerative diseases.”

https://pubmed.ncbi.nlm.nih.gov/39892452/

https://www.sciencedirect.com/science/article/pii/S0014299925000767?via%3Dihub

Cannabidiol Ameliorates Doxorubicin-Induced Myocardial Injury via Activating Hippo Pathway

Posted on January 29, 2025 by David

“Background: Doxorubicin (DOX) is a chemotherapeutic agent widely used for cancer treatment and has non-negligible cardiotoxicity. Some previous studies have reported that cannabidiol (CBD) has cardioprotective effects. In this study, we evaluated the protective effects of CBD against DOX-induced cardiomyocyte injury, and explored the downstream molecular mechanism.

Methods and materials: GSE193861, containing healthy myocardial tissues and myocardial tissues with DOX-induced injury, was analyzed to screen for the involved proteins and pathways. Molecular docking was performed to identify candidate drugs. After H9c2 cells were treated with DOX and CBD, their viability, oxidative stress, and apoptosis were assessed. After YAP depletion, the role of the Hippo pathway in CBD function was investigated. C57BL/6 mice were treated with DOX to establish an in vivo model, and CBD and verteporfin (VP) were used to treat the mice. Histological analyses and immunofluorescence were used to evaluate myocardial tissue injury, and apoptosis and oxidative stress of the myocardial tissues were also analyzed. Western blotting was used to investigate the regulatory effects of CBD on the Hippo and apoptosis-related pathways.

Results: Bioinformatic analysis suggested that the Hippo pathway was a crucial pathway involved in DOX-induced myocardial injury. Molecular docking showed that CBD targeted multiple regulators of the Hippo pathway. CBD showed cardioprotective effects against DOX-induced myocardial injury both in vitro and in vivo and regulated Hippo pathway activity in cardiomyocytes. After inactivation of the Hippo pathway by YAP knockdown or VP intervention, the protective effects of CBD were reversed.

Conclusion: For the first time, we revealed that CBD is likely to reduce DOX-induced myocardial injury by regulating the Hippo signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/39876987/

“Overall, this study reports that CBD alleviates DOX-induced myocardial injury by regulating the Hippo pathway.”

https://www.dovepress.com/cannabidiol-ameliorates-doxorubicin-induced-myocardial-injury-via-acti-peer-reviewed-fulltext-article-DDDT

Permeability of active ingredients of cannabis and possibility for further antituberculosis drug development

Posted on January 27, 2025 by David

“Background

Cannabis is presently legalized in several countries owing to its medicinal property. The antibacterial properties of active ingredients of cannabis have been mentioned. Their usefulness in the management of tuberculosis is very interesting.

Materials and methods

The authors performed a bioinformatics analysis to assess the possibility of important active ingredients of cannabis.

Results

Based on the present analysis, it can be seen that the studied active ingredients of cannabis can effectively pass through the cell wall of Mycobacterium tuberculosis, indicating the possibility of further pharmacological actions.

Conclusion

The active ingredients of cannabis are the possible new targets for further antituberculosis drug development.”

“Cannabis is presently legalized in several countries owing to its medicinal properties[³]. The antibacterial property of active ingredients of cannabis is mentioned. Their usefulness in management of tuberculosis is very interesting. In the present study, the authors studied the permeability of active ingredients detectable in cannabis. The studied ingredients are the important main ingredients including tetrahydrocannabinol (THC) and cannabidiol (CBD)[⁴]. The study is a useful basic study for further antituberculosis drug search.”

“Here, it can be shown that the studied active ingredients of cannabis have the possibility to pass into the mycobacterial cell. Difference in permeability based on the size of the ingredients can be observed. Of interest, it can confirm the previous reports that the Mycobacteria can cause biotransformation of CBD[⁹], delta-8-THC[⁹], and delta-9 THC[¹⁰]. This observation can show that CHD, delta-8-THC, and delta-9 THC can be a further target for antituberculosis drug development. The three studied main active ingredients of cannabis are reported for bactericidal activity for some gram-positive bacteria.”

“The present study is a medical pharmacoinformatics study. It can confirm that the active ingredients of cannabis are the possible new targets for further antituberculosis drug development.”

https://journals.lww.com/ecdt/fulltext/2021/70030/permeability_of_active_ingredients_of_cannabis_and.3.aspx

Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature

Posted on January 26, 2025 by David

“Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain’s immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system.

Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework.

This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science.

The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa,

Cannabis sativa,

and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation.

Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.”

https://pubmed.ncbi.nlm.nih.gov/39861194/

“Addressing neuroinflammation to reduce disease severity and improve patient outcomes is a promising strategy against neurodegeneration. From a molecular perspective, there are several conventional drug targets for neuroinflammation, such as enzymes, receptors, and ion channels. However, the high cost of synthetic drugs presents a challenge, emphasizing the need for alternative approaches. This has heightened interest in naturally occurring medicinal plants known for their antioxidant, anti-inflammatory, and neuroprotective properties. These plants are often more cost-effective and have been safely utilized in treatments for thousands of year.”

https://www.mdpi.com/1424-8247/18/1/133

www.thctotalhealthcare.com

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