Cannabinoid Use in Pediatric Epilepsy

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“Cannabidiol has shown promising effects on reducing seizure frequency in children and adults with selected epilepsy syndromes. In this narrative brief review, we provide an update on the use of cannabidiol in pediatric epilepsy including the indications for its use, clinical efficacy, adverse effects, requirements for monitoring and regulations.”

https://pubmed.ncbi.nlm.nih.gov/40244307/

https://link.springer.com/article/10.1007/s13312-025-00015-7

Cannabinoid Receptors Reduced Early Brain Damage by Regulating NOX-2 and the NLRP3 Inflammasome in an Animal Model of Intracerebral Hemorrhage

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“Background: Intracerebral hemorrhage (ICH) is a leading cause of death and disability worldwide. Following the initial mechanical injury caused by hematoma expansion, a secondary injury occurs, characterized by the production of reactive oxygen species (ROS) generated by NOX-2 and neuroinflammation, which is exacerbated by the upregulation of the NLRP3 inflammasome. These conditions collectively aggravate brain damage.

The endocannabinoid system (ECS), through the activation of the cannabinoid receptors, has demonstrated neuroprotective properties in various models of brain injury. However, the role of the ECS during ICH remains poorly understood, particularly regarding the action of the CB1 receptor in the activation of NOX-2 and the inflammasome. The present study investigates the neuroprotective effects of the cannabinoid receptor agonist WIN55,212-2 in an ICH animal model, specifically examining the roles of NLRP3 and NOX-2.

Methods: Male C57BL/6 mice were subjected to ICH through an intracerebral injection of collagenase, followed by intraperitoneal administration of WIN55,212-2 and/or MCC950, a selective NLRP3 inhibitor. Various outcome measures were employed, including assessments of motor activity, hematoma volume, brain water content, and blood-brain barrier (BBB) permeability, which was evaluated using Evans blue assay. Additionally, the activity of NOX and the protein levels of crucial markers such as CB1, gp91phox, NLRP3, AQP4, and caspase-1 were measured via western blot analysis.

Result: The findings demonstrate that ICH induced a significant brain lesion characterized by hematoma formation, edema, BBB disruption, and subsequent motor impairments in the affected mice. Notably, these detrimental effects were markedly reduced in animals treated with WIN55,212-2. The study also revealed an activation of both NOX-2 and NLRP3 in response to ICH, which was reduced by cannabinoid receptor activation. Furthermore, the pharmacological inhibition of NLRP3 using MCC950 also led to a reduction in hematoma size, edema, and motor impairment secondary to ICH.

Conclusions: These results support a neuroprotective role of the cannabinoid receptor activation during ICH and suggest the involvement of NOX-2 and NLRP3.”

https://pubmed.ncbi.nlm.nih.gov/40245261/

Utilizing ADMET Analysis and Molecular Docking to Elucidate the Neuroprotective Mechanisms of a Cannabis-Containing Herbal Remedy (Suk-Saiyasna) in Inhibiting Acetylcholinesterase

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“Alzheimer’s disease is characterized by the degeneration of cholinergic neurons, which is primarily driven by the acetylcholinesterase (AChE) enzyme and oxidative stress.

This study investigated the therapeutic potential of the cannabis-containing herbal remedy Suk-Saiyasna in alleviating amyloid β42 (Aβ42)-induced cytotoxicity in SH-SY5Y cells.

The DPPH radical-scavenging activity and inhibitory effects on AChE were evaluated in vitro. The AChE inhibitory potential of 167 ligands, including cannabinoids, flavonoids, terpenoids, and alkaloids derived from Suk-Saiyasna, was assessed using ADMET analysis and molecular docking techniques.

The results demonstrated that the Suk-Saiyasna extract exhibited a DPPH radical scavenging effect with an IC50 value of 27.40 ± 1.15 µg/mL and notable AChE inhibitory activity with an IC50 of 1.25 ± 0.35 mg/mL. Importantly, at a concentration of 1 µg/mL, the extract significantly protected cells from Aβ42-induced stress compared to controls.

Docking studies revealed that delta-9-tetrahydrocannabinol (Δ9-THC), mesuaferrone B, piperine, β-sitosterol, and chlorogenic acid exhibited substantial binding affinities to AChE, surpassing reference drugs like galantamine and rivastigmine. Furthermore, in silico ADMET predictions indicated that Δ9-THC and piperine possessed favorable pharmacokinetic profiles, including solubility, absorption, and blood-brain barrier permeability, with no neurotoxicity or carcinogenicity associated with Δ9-THC.”

https://pubmed.ncbi.nlm.nih.gov/40243991/

“This study highlighted the potential of the Suk-Saiyasna herbal remedy in developing novel neuroprotective compounds for Alzheimer’s disease. The extracts of Suk-Saiyasna demonstrated significant antioxidant and acetylcholinesterase inhibitory activities, indicating their therapeutic applications. Molecular docking studies identified various active constituents with promising binding affinities, reinforcing their potential as acetylcholinesterase inhibitors.

Additionally, ADME predictions indicated favorable properties for Δ9-THC and piperine, underscoring their ability to cross the blood–brain barrier, which is crucial for neuroprotective effects. The safety evaluation of the extracts revealed moderate toxicity for piperine and Δ9-THC, while mesuaferrone B and chlorogenic acid displayed a safer profile. The inactivity of these compounds regarding hepatotoxicity and neurotoxicity further supported their potential use in therapeutic settings. However, concerns regarding carcinogenicity associated with piperine, donepezil, and galantamine necessitate rigorous safety assessments.

Overall, the findings from this research provide a foundation for the future exploration of Suk-Saiyasna as a promising source of natural antioxidants and neuroprotective agents.”

https://www.mdpi.com/1422-0067/26/7/3189

Therapeutic Potential of Cannabidiol Cyclodextrin Complex in Polymeric Micelle and Tetrahydrocurcumin Cyclodextrin Complex Loaded in Hydrogel to Treat Lymphedema

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“Cannabidiol (CBD) and tetrahydrocurcumin (THC) have demonstrated anti-inflammatory activity as well as generating new lymph vessels. We present the formulations and evaluations of CBD and THC loaded in hydrogels for the treatment of lymphedema to promote angiogenesis of lymph vessels and an anti-inflammatory response.

Six CBD-THC hydrogel formulations were prepared and evaluated. The hydrodynamic particle sizes were 302.0-545.1 nm and the zeta potentials were from -58.80 to -33.63 mV. The hydrogel pHs were 6.43-6.54.

The hydrogel formulations were non-toxic for both CBD (<25 µg/mL) and THC (<12.5 µg/mL). It was observed that high-molecular-weight hyaluronic acid in hydrogel affected collagen production. Hydrogel formulations at 2 µg/mL of CBD and 1 µg/mL of THC induced human dermal lymphatic endothelial cell tube formation.

CBD-THC hydrogel formulations showed a notable ability to induce angiogenesis, which suggested its potential effectiveness in promoting new lymphatic vessel formation. Moreover, CBD-THC hydrogels showed anti-inflammatory properties. Further research is needed to ensure these treatments effectively enhance lymphatic repair.”

https://pubmed.ncbi.nlm.nih.gov/40244338/

“In conclusion, CBD-THC hydrogels offer a multifunctional therapeutic strategy for lymphedema by combining angiogenesis promotion, anti-inflammatory effects, and injectable gelation behavior.”

https://www.mdpi.com/1422-0067/26/7/3428

Cannabinerol Restores mRNA Splicing Defects Induced by β-Amyloid in an In Vitro Model of Alzheimer’s Disease: A Transcriptomic Study

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“Alzheimer’s disease (AD) is the most common form of dementia, characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles, leading to neuronal loss and cognitive impairments. Recent studies have reported the dysregulation of RNA splicing in AD pathogenesis.

Our previous transcriptomic study demonstrated the neuroprotective effect of the phytocannabinoid cannabinerol (CBNR) against the cell viability loss induced by Aβ in differentiated SH-SY5Y cells. This study also highlighted the deregulation of genes involved in mRNA splicing after Aβ exposure or CBNR pre-treatment.

Here, we investigated whether CBNR could restore the splicing defects induced by Aβ in an AD in vitro model.

Using the rMATS computational tool for detecting differential alternative splicing events (DASEs) from RNA-Seq data, we obtained 96 DASEs regulated in both conditions and, remarkably, they were all restored by CBNR pre-treatment. The pathway analysis indicated an over-representation of the “Alzheimer’s disease-amyloid secretase pathway”. Additionally, we observed that Aβ exposure increased the frequency of retained introns (RIs) among the shared DASEs, and that this frequency returned to normality by CBNR pre-treatment. Interestingly, most of these RIs contain a premature in-frame stop codon within the RNA sequence. Finally, analyzing the DASE regions for miRNA hybridization, we found 33 potential DASE/miRNA interactions that were relevant in AD pathogenesis.

These findings revealed a novel trans-gene regulation by CBNR, potentially explaining part of its neuroprotective role. This is the first study demonstrating the involvement of a cannabinoid in the regulation of mRNA splicing in an AD model.”

https://pubmed.ncbi.nlm.nih.gov/40243843/

“In conclusion, we documented for the first time that a cannabinoid, CBNR, is able to regulate AS in an in vitro AD model. CBNR pre-treatment restored the splicing defects produced by Aβ exposure, involving genes also highly associated with AD. Moreover, thanks to this mechanism, CBNR probably counteracts the Aβ-induced mis-regulation of genes, due to premature stop codons and miRNA or lncRNA targeting. This work improves our knowledge of the molecular mechanisms that can be potentially useful in treating AD, corroborating the fact that drugs targeting post-transcriptional splicing processes could be considered novel and valid choices in neuroprotection and prevention issues.”

https://www.mdpi.com/1422-0067/26/7/3113

The Identification of Novel Anti-Inflammatory Effects of Cannabigerol in the Kidney Tissue of Rats Subjected to a High-Fat High-Sucrose Diet

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“The inflammatory state is a significant factor associated with diabetic kidney disease (DKD), making it one of the significant causes of chronic kidney disease. Despite the availability of data, there is a lack of targeted treatment strategies for diabetes-related kidney disorders.

The aim of our study was to determine the impact of cannabigerol (CBG) on lipid precursors for inflammatory mediators during DKD development.

A six-week experiment was conducted on male Wistar rats fed standard (Control) or high-fat high-sucrose (HFHS) diets. For the last 14 days of the experiment (5th and 6th weeks), half of the rats from the Control and HFHS groups intragastrically received CBG solution. Gas-liquid chromatography (GLC) was used to measure the activities of n-6 and n-3 polyunsaturated fatty acid (PUFA) metabolic pathways and the concentrations of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in selected lipid fractions. Immunoblotting was performed to assess the expression of proteins involved in the regulation of the inflammatory state. A multiplex immunoassay kit was used to determine kidney toxicity biomarker levels.

Our results revealed that CBG administration to rats fed an HFHS diet decreased n-6 PUFA biosynthetic pathway activity in phospholipid (PL) and triacylglycerol (TAG) and increased n-3 PUFA biosynthetic pathway activity in TAG and free fatty acid (FFA). We also observed a reduction in the AA concentration in PL, FFA, and diacylglycerol (DAG). CBG supplementation reduced the level of kidney damage biomarkers, such as osteopontin (OPN).

Our observations confirm that CBG has potential anti-inflammatory properties and may be successfully used for further research to seek targeted therapies of inflammatory disorders, including diabetic kidney disease progression.”

https://pubmed.ncbi.nlm.nih.gov/40243749/

“These results suggest that cannabigerol may have potential anti-inflammatory effects and could be used as a therapeutic agent to support the treatment of inflammatory-related diseases.”

https://www.mdpi.com/1422-0067/26/7/3114

Preparation, Modification, Food Application, and Health Effects of Protein and Peptide from Hemp (Cannabis sativa L.) Seed: A Review of the Recent Literature

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“Hemp is a multiuse crop used for fiber, food, and medicinal purposes. The seed of hemp has attracted great attention as a good plant protein resource with remarkable nutritional and biological properties. However, the application of hemp seed protein (HSP) is limited due to its unsatisfactory functional properties. Physical, chemical, and biological technologies have been explored to modify the structure of HSP and improve its functionality. The investigation of the biological activity of HSP and its derived peptide to deal with intestinal, metabolic, and muscle concerns has broadened its utilization in healthy products. Therefore, the current review is performed to summarize the recent research progress on the novel extraction and modification of HSP, as well as the purification and identification of active peptide. The multi-functional multi-bioactive properties and adverse effects of HSP and peptide are also depicted to facilitate their potential applications in the food industry.”

https://pubmed.ncbi.nlm.nih.gov/40238243/

“This review highlights the potential of hemp seed protein and peptides as emerging valuable bioactive ingredients to improve food quality and develop functional products. Furthermore, the extraction and modification methods of HSP, as well as the preparation and identification of active peptides, are summarized. Despite hemp seed protein being characterized as a good source of essential amino acids with multiple health benefits, the use of the cannabis plant has been stigmatized in most countries in the world due to its psychoactive effects. Accordingly, increasing science popularization and raising public acceptance about hemp is necessary to facilitate the promotion of related products. And more research is highly recommended to confirm the potential allergens in hempseed protein. Moreover, although in silico analysis can predict hemp seed active peptides properties and sequence as time- and cost-effective alternative tools, more in vitro analyses, animal tests, and human intervention trials are still required to better support their application in daily diets and as a functional food. In conclusion, this plant-based health protein offers an excellent opportunity to meet the demands of the food industry and benefit human wellness.”

https://www.mdpi.com/2304-8158/14/7/1149


Research mapping of cannabinoids and endocannabinoid system in cancer over the past three decades: insights from bibliometric analysis

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“Background: The cannabinoids and endocannabinoid system are thought to play critical roles in multiple signaling pathways in organisms, and extensive evidence from preclinical studies indicated that cannabinoids and endocannabinoids displayed anticancer potential. This study aimed to summarize the research of cannabinoids and endocannabinoid system in cancer through bibliometric analysis.

Methods: Relevant literature in the field of cannabinoids and endocannabinoid system in cancer published during 1995-2024 were collected from the Web of Science Core Collection database. VOSviewer and SCImago Graphica were applied to perform bibliometric analysis of countries, institutions, authors, journals, documents, and keywords.

Results: A total of 3,052 publications were identified, and the global output exhibited a generally upward trend over the past 3 decades. The USA had the greatest number of publications and citations in this research field. Italian National Research Council led in terms of publication, while Complutense University of Madrid had the highest total citations. Vincenzo Di Marzo was the leading author in this field with the greatest number of publications and citations. The co-occurrence of keywords revealed that the research frontiers mainly included “cannabinoids”, “endocannabinoid system”, “cancer”, “anandamide”, “cannabidiol”, “cannabinoid receptor”, “apoptosis”, and “proliferation”.

Conclusion: Our results revealed that the research of cannabinoids and endocannabinoid system in cancer would receive continuous attention. The USA and Italy have made remarkable contributions to this field, supported by their influential institutions and prolific scholars. The research emphasis has evolved from basic functional characterization to mechanistic exploration of disease pathways and translational applications within multidisciplinary framework.”

https://pubmed.ncbi.nlm.nih.gov/40242437/

“In this study, we conducted a comprehensive bibliometric analysis on the research of cannabinoids and endocannabinoid system in cancer over the past 3 decades. Our results would provide referable guidance for the understanding of research emphasis on this topic, offering insights for clinical interventions and scientific inquiries.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1540619/full

Cannabinoids as Multitarget Drugs for the Treatment of Autoimmunity in Glaucoma

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“Diseases of multifactorial origin like neurodegenerative and autoimmune diseases require a multitargeted approach.

The discovery of the role of autoimmunity in glaucoma and retinal ganglionic cell (RGC) death has led to a paradigm shift in our understanding of the etiopathology of glaucoma. Glaucoma can cause irreversible vision loss that affects up to an estimated 3% of the population over 40 years of age. The current pharmacotherapy primarily aims to manage only intraocular pressure (IOP), a modifiable risk factor in the glaucomatous neurodegeneration of RGCs. However, neurodegeneration continues to happen in normotensive patients (where the IOP is below a reference value), and the silent nature of the disease can cause significant visual impairment and take a massive toll on the healthcare system.

Cannabinoids, although known to reduce IOP since the 1970s, have received renewed interest due to their neuroprotective, anti-inflammatory, and immunosuppressive effects on autoimmunity. Additionally, the role of the gut-retina axis and abnormal Wnt signaling in glaucoma makes cannabinoids even more relevant because of their action on multiple targets, all converging in the pathogenesis of glaucomatous neurodegeneration. Cannabinoids also cause epigenetic changes in immune cells associated with autoimmunity.

In this Review, we are proposing the use of cannabinoids as a multitargeted approach for treating autoimmunity associated with glaucomatous neurodegeneration, especially for the silent nature of glaucomatous neurodegeneration in normotensive patients.”

https://pubmed.ncbi.nlm.nih.gov/40242585/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00583

Meta-analysis of medical cannabis outcomes and associations with cancer

“Background: Growing bodies of evidence suggest that cannabis may play a significant role in both oncological palliative care and as a direct anticarcinogenic agent, but classification as a Schedule I substance has complicated research into its therapeutic potential, leaving the state of research scattered and heterogeneous. This meta-analysis was conducted to determine the scientific consensus on medical cannabis’ viability in cancer treatment.

Objective: The aim of this meta-analysis was to systematically assess the existing literature on medical cannabis, focusing on its therapeutic potential, safety profiles, and role in cancer treatment.

Methods: This study synthesized data from over 10,000 peer-reviewed research papers, encompassing 39,767 data points related to cannabis and various health outcomes. Using sentiment analysis, the study identified correlations between cannabis use and supported, not supported, and unclear sentiments across multiple categories, including cancer dynamics, health metrics, and cancer treatments. A sensitivity analysis was conducted to validate the reliability of the findings.

Results: The meta-analysis revealed a significant consensus supporting the use of medical cannabis in the categories of health metrics, cancer treatments, and cancer dynamics. The aggregated correlation strength of cannabis across all cancer topics indicates that support for medical cannabis is 31.38× stronger than opposition to it. The analysis highlighted the anti-inflammatory potential of cannabis, its use in managing cancer-related symptoms such as pain, nausea, and appetite loss, and explored the consensus on its use as an anticarcinogenic agent.

Discussion: The findings indicate a strong and growing consensus within the scientific community regarding the therapeutic benefits of cannabis, particularly in the context of cancer. The consistent correlation strengths for cannabis as both a palliative adjunct and a potential anticarcinogenic agent redefine the consensus around cannabis as a medical intervention.

Conclusion: The consistency of positive sentiments across a wide range of studies suggests that cannabis should be re-evaluated within the medical community as a treatment option. The findings have implications for public health research, clinical practice, and discussions surrounding the legal status of medical cannabis. These results suggest a need for further research to explore the full therapeutic potential of cannabis and address knowledge gaps.”

“The data presented here indicate that cannabis has a well-established role in managing symptoms related to cancer and may have both direct and indirect anticancer properties, which challenges the notion that it has no accepted medical use.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1490621/full