Multi-level inhibition of SARS-CoV-2 invasion by cannabidiol and epigallocatechin gallate

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“The global pandemic coronavirus disease 2019 (COVID-19) attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study aimed at combination therapies with natural polyphenolic compounds, such as cannabidiol (CBD), green tea polyphenols (Tea-poly), epigallocatechin gallate (EGCG) and theaflavin (TF), to investigate in vitro their inhibitory effects on virus invasion and viral spike (S) protein expression.

Among the compounds tested, CBD and Tea-poly exhibited the most significant inhibitory effects on virus entry, comparable to the positive control chloroquine (CQ). EGCG showed the strongest suppression of the expression of the S protein, while CBD remarkably decreased ACE2 expression. CoIP-MS revealed eleven S-protein-interacting proteins that were significantly affected by EGCG.

Transcriptome analysis demonstrated similar trends of CBD and EGCG in the modulation of many SARS-CoV-2-associated genes, with CBD showing greater impact on the gene profile than EGCG. GO and KEGG functional enrichment analyses revealed overlapping pathways of EGCG and CBD, including DNA repair, cell-cycle, and ER-, spliceosome- and ribosome-related processes.

The combined use of CBD and EGCG can complement each other’s advantages in inhibiting the invasion and reinvasion process of the virus at multiple levels, while minimizing the adverse effects of ACE2 expression level changes.

Findings in this work offer new information for developing multi-level therapeutic strategies to control SARS-CoV-2 infection and, specifically, provide a novel antiviral agent combination of CBD and EGCG for the control of COVID-19.”

https://pubmed.ncbi.nlm.nih.gov/40460494/

“Cannabidiol (CBD), one of the well-known pharmacologically active ingredients from the extracts of cannabis (Cannabis sativa L.), exerts a wide range of anti-inflammatory and immunomodulatory properties, leading to the presumption that CBD might be a potent agent also against COVID-19. Indeed, CBD may alleviate systemic symptoms of COVID-19 and reduce respiratory distress as well as cytokine storm reactions. Additionally, CBD may prime components of the innate immune system, enhancing innate anti-viral response to viral genes.”

“Green tea polyphenols, along with their most abundant bioactive constituent epigallocatechin gallate (EGCG), have been recognized as multi-functional compounds with broad-spectrum antiviral effects in addition to anti-inflammatory, antioxidative, antibacterial and antiproliferative properties.”

“To summarize, natural compounds, such as CBD and EGCG, have the benefits of being widely available, inexpensive, and low in toxicity for supplementing conventional therapies. Our findings in this study indicate great potentials of CBD and EGCG for novel therapeutics against SARS-CoV-2 infection as a multi-level antiviral strategy.”

https://www.sciencedirect.com/science/article/abs/pii/S0042682225001928?via%3Dihub

19 patients report seizure freedom with medical cannabis oil treatment for drug-resistant epilepsy: a case series

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“Purpose: Seizure freedom (SF) is the primary goal of epilepsy treatment. More treatments that produce SF in drug-resistant epilepsy (DRE) are needed. Cannabis-based products for medicinal use (CBPMs) containing cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), administered as oils, have been shown to induce SF in DRE. However, there remains a paucity of published real-world evidence in both pediatrics and adults on SF resulting from CBPM therapy.

Methods: This is a retrospective case series at an outpatient neurology clinic in Toronto, Canada, on patients with DRE who experienced significant SF during CBPM treatment. All patients were treated via the clinic’s stepwise treatment protocol with CBPM oils only. The study describes clinical features of patients and their CBPM-related SF.

Results: We report 19 DRE cases that experienced SF; 15 pediatric, 4 adults. The median cumulative SF duration was 245 days, split between continuous SF periods lasting at least 90 days. Five patients had continuous SF periods lasting ≥ 1 year. Most patients used CBD+THC regimens. Three patients weaned all concomitant ASMs. Adverse events (AEs) were reported by half of the patients.

Conclusion: The results of the study support prioritizing CBPMs in cases of DRE. It also supports research into identifying clinical and biological biomarkers for DRE cases that may achieve SF under CBPM treatment. Lastly, the study supports improving the accessibility of CBPMs, using SF as a primary outcome in future CBPM epilepsy trials, and assessing the role of THC in reducing seizures.”

https://pubmed.ncbi.nlm.nih.gov/40458487/

“A promising treatment for DRE are cannabis-based products for medicinal use (CBPMs) containing variations of cannabinoids, such as cannabidiol (CBD), Δ-9-tetrahydrocannabinol (THC) and other cannabis plant products in an oil formulation.”

“This study reports Real World Evidence from 19 patients with Drug Resistant Epilepsy who experienced Seizure Freedom due to Cannabis based medicinal products therapy. The SF rates observed in this study complement existing literature that reports rates of at least 4%, higher than the 1% observed with established ASMs.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1570531/full

National Multicenter Cohort Study: Adjunctive Cannabidiol-Enriched Cannabis Oil for Pediatric Drug-Resistant Epilepsy Treatment in Thailand

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“Background: Several studies have reported the effectiveness and tolerability of cannabidiol (CBD)-enriched oil adjunctive treatment in children with drug-resistant epilepsy. This is the first multicenter cohort study of medical-grade CBD-enriched drugs in pediatric drug-resistant epilepsy in Thailand.

Methods: A prospective observational study was conducted across 19 Thai government hospitals between 2021 and 2023. The study aimed to assess CBD-enriched adjunctive treatment in pediatric drug-resistant epileptic patients with various etiologies ensuring a follow-up period of at least three months including cases wherein the medication was discontinued before three months.

Results: Of 101 patients, 42% were male with a median age of 10 years, experiencing a seizure frequency of 75 per month, and having failed treatment with an average of seven types of antiseizure medications. The median follow-up duration was 15 months with a median modal CBD dose of 6 mg/kg/day. The ≥50% seizure reduction rate and the median monthly total seizure reduction showed consistent improvement with reductions at three-, six-, nine-, and 12-month and the latest follow-up visits. Most seizure types responded positively to treatment, except for complex motor seizures. The effective CBD dose varied within a range of 1-15 mg/kg/day. Adverse events were reported in 92% of patients, predominantly mild (95%) and including somnolence, increased liver enzymes, anorexia, and irritability. Thirty-three patients discontinued CBD, with 57% due to intolerable adverse events, 30% ineffectiveness, and 12% noncompliance.

Conclusions: The Thai medical-grade CBD-enriched oil is effective and tolerable for at least 12 months of adjunctive treatment in pediatric drug-resistant epilepsy in Thailand.”

https://pubmed.ncbi.nlm.nih.gov/40460512/

“Cannabidiol (CBD) has emerged as a promising therapeutic option, demonstrating efficacy in reducing seizures in children with drug-resistant epilepsy.”

“In conclusion, the Thai medical grade CBD-enriched oil is effective and well tolerated for at least 12 months of continuous adjunctive treatment in pediatric drug-resistant epilepsy in Thailand even at lower CBD doses than those used in other CBD-purified studies.”

https://www.pedneur.com/article/S0887-8994(25)00111-0/fulltext

Cannabidiol and microRNAs: shared cellular targets and new insights for developing anti-seizure modalities

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“Cannabidiol (CBD) and 9-tetrahydrocannabinol (THC) are the two main components of cannabis that provide its therapeutic benefits.

CBD has been extensively studied for its role in reducing seizures, among its many other uses. While the exact mechanisms by which CBD works to relieve seizures have not yet been fully determined, it is evident that CBD effectively diminishes seizure activity and is now being used as an approved treatment for severe forms of non-responsive epilepsy.

As essential components of several biological processes, microRNAs (miRNAs) are crucial for achieving optimal cellular functioning. During the past few years, there has been an increasing interest in elucidating the functional significance of microRNAs in epilepsy. Yet, there is still considerable ambiguity regarding the precise mechanisms by which miRNAs are involved in seizure disorders and also their direct interaction with CBD.

Herein, we seek to present an overview of the varying mechanisms by which CBD offers therapeutic benefits concerning seizures. Accordingly, we highlighted the shared molecular targets between microRNAs and CBD in alleviating seizure symptoms to shed light on the ways in which new therapeutic and diagnostic modalities could be shaped in the future.”

https://pubmed.ncbi.nlm.nih.gov/40461016/

https://academic.oup.com/jpp/advance-article-abstract/doi/10.1093/jpp/rgaf039/8156016?redirectedFrom=fulltext&login=false

Cannabidiol ameliorates seizures and neuronal damage in ferric chloride-induced posttraumatic epilepsy by targeting TRPV1 channel

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“Ethnopharmacological relevance: Posttraumatic epilepsy (PTE) is an acquired epilepsy caused by traumatic brain injury (TBI). From Mesopotamian civilization to Eastern medical classics, the use of Cannabis for anticonvulsant purposes has spanned three millennia of medical history. As a non-psychoactive plant extract of Cannabis, cannabidiol (CBD) has attracted considerable attention in epilepsy-related treatment. However, whether CBD exhibits an anticonvulsant effect against PTE and its underlying molecular mechanisms remains to be elucidated.

Aim of the study: This study aims to investigate the anticonvulsant and neuroprotective effect of CBD on PTE, as well as its molecular mechanisms.

Methods: Ferric chloride (FeCl3)-induced PTE rat models were constructed in normal rats and brain-localized transient receptor potential vanilloid type 1 (TRPV1) overexpression rats. The anticonvulsant effects of CBD were evaluated by epileptic behavioral scoring and electroencephalogram (EEG) monitoring. The neuroprotective effect was measured by histopathological staining of the brain tissues. Immunofluorescence, western blot, q-PCR and Ca2+ fluorescence intensity detection were employed to investigate the mechanisms of CBD on PTE rats.

Results: CBD significantly reduced the seizure severity and brain damage in FeCl3-induced PTE rat models. Besides, EEG data showed decreased amplitude, total power, and spike wave discharges in PTE rats pretreated with CBD. Moreover, CBD suppressed the phosphorylation of heat shock factor 1 (HSF1) by targeting TRPV1, thereby specifically inhibiting the stress-induced heat shock protein 70 (HSP70) increase in the brain-localized TRPV1 overexpression rats.

Conclusion: CBD exerts an anticonvulsant and neuroprotective effect on PTE rats by regulating the TRPV1/HSF1/HSP70 pathway and may be a potential drug for the prophylactic treatment of PTE.”

https://pubmed.ncbi.nlm.nih.gov/40449694/

“CBD may be a potential drug for the prophylactic treatment of PTE.”

https://www.sciencedirect.com/science/article/abs/pii/S0378874125007597?via%3Dihub

Complex forming properties of cannabinoid acids in a green solvent and bioassays focused on gastric disease caused by Helicobacter pylori infection

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“The main objective of the present study was to determine the protolytic and coordination properties of two bioactive cannabinoid acids (cannabidiolic acid and cannabigerolic acid) in ethyl alcohol-water mixture (50/50, v/v).

The complexation properties of these acids with copper(II) and zinc(II) ions were determined by potentiometric and ESI-MS methods. UV-Vis absorption spectra for the copper(II) systems confirmed the speciation models with one type of complex indicating coordination with completely deprotonated dinegative ligand molecule. The occurrence of precipitation at lower pH values limited the ability to determine complexes under these conditions.

The research also aimed to identify potential biological and medicinal applications of cannabinoid acids and their complexes with zinc(II). The ability of these compounds to influence the growth of human Hs68 skin fibroblasts and AGS gastric adenocarcinoma cells was investigated. Furthermore, these structures were tested against Helicobacter pylori strains, one of the factors promoting gastric cancer development.

At concentrations that were not-toxic to healthy cells (after dilution of the solutions, the composition of the ethanol/water mixture was approximately 1/99, v/v), the ligands exhibited bacterial inhibitory activity and cytotoxic properties against AGS cancer cells. Zinc(II) complexes, on the other hand, being biologically safe for all cells, had strong antibacterial properties, both inhibitory and bactericidal.”

https://pubmed.ncbi.nlm.nih.gov/40436988/

“Naturally occurring compounds known as plant cannabinoids or phytocannabinoids, responsible for the physiological effects of cannabis, have been used medicinally for thousands of years.”

https://www.nature.com/articles/s41598-025-03442-5

Nutritional Composition and Functional Properties of ‘Beldiya’ Hemp Seed and Oil: A Sustainable Local Resource from Northern Morocco for Health and Nutrition

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“The importance of hemp seeds (Cannabis sativa L.) as a nutrient-rich resource in agricultural studies is often underestimated by cannabis farmers, who tend instead to treat them as byproducts.

The purpose of this study was to assess the nutritional composition of Beldiya, a distinct ecotype of hemp seed from the northern regions of Morocco. The proximal composition, mineral content, total phenolic content, tocopherol content, fatty acid profile and lipid health indices of the seeds were assessed.

The results revealed that the ‘Beldiya’ ecotype (Be-ecot) contained 94.08% dry matter, 32.81% oil, 24.84% protein, 27.54% fiber and 4.29% ash. It is rich in total phenolic content (201.88 mg GAE/100 g) and total flavonoid content (69.77 mg QE/100 g). The predominant tocopherol in its oil is γ-tocopherol (409.72 mg/kg), with δ-tocopherol (21.91 mg/kg) and α-tocopherol (18.89 mg/kg), contributing to a total tocopherol content of 450.82 mg/kg.

The main fatty acids in the oil are linoleic acid (51.02%), oleic acid (18.05%), linolenic acid (16.46%) and palmitic acid (7.68%). The ratio of n-6 to n-3 polyunsaturated fatty acids (PUFAs) is 3:1, which corresponds to the recommended dietary balance for these essential fatty acids.

These results highlight the nutritional benefits and balanced composition of hemp seeds, highlighting their potential as valuable edible food sources for promoting a healthy lifestyle.”

https://pubmed.ncbi.nlm.nih.gov/40451822/

https://www.jstage.jst.go.jp/article/jos/74/6/74_ess25015/_article

Exploring the Phytochemical and Toxicological Profile of Moroccan Cannabis Sativa L. Leaves Extract: Behavioral, Histological, and Oxidative Stress Assessments

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“Ethnopharmacological relevance: Cannabis sativa has been traditionally used in Moroccan medicine for centuries, either for its psychoactive or therapeutic effects. However, the safety profile of extracts from macerated leaves remains poorly documented in the scientific literature.

Aim of the study: This study, for the first time, evaluates the phytochemical composition and the toxicological profile of an ethanolic extract of Cannabis sativa (CEE) leaves in mice, focusing on behavioral effects, oxidative stress markers, and histopathological examination.

Materials and methods: The CEE was evaluated using HPLC analysis, secondary metabolites quantification, and in vitro antioxidant assays. Acute oral toxicity was assessed in female mice at doses from 500 to 3000 mg/kg, while oral subacute toxicity was evaluated over 7 days in male mice receiving 10, 30, or 50 mg/kg of CEE. Behavioral assessments included the open field, rotarod, and elevated plus maze tests. Additionally, body weight gain, organ coefficients, organ edema, oxidative stress markers, and histopathology of the brain, liver, kidneys, spleen, and testes were examined.

Results: CEE exhibited substantial amounts of polyphenols, flavonoids, tannins, and saponins, with notable antioxidant activity (DPPH IC50: 289.01 ± 0.003 μg/mL; FRAP IC50: 57.29 ± 6.7 μg/mL). No mortality was observed in the acute toxicity study. The 7-day treatment caused no sedation or motor impairment, rather, it showed anxiolytic effects. A significant increase in body weight gain was noted, particularly at 10 mg/kg, while no changes in organ coefficients or signs of organ edema were detected. However, MDA and catalase activity increased in the liver and brain at 50 mg/kg. Histopathological examination revealed signs of cellular stress without severe tissue damage.

Conclusions: CEE appears to be safe at moderate doses, with an LD50 above 3000 mg/kg. Further studies are needed to assess long-term effects.”

https://pubmed.ncbi.nlm.nih.gov/40436124/

https://www.sciencedirect.com/science/article/abs/pii/S0378874125007457?via%3Dihub

Cannabidiolic Acid Rescues Deficits in Hippocampal Long-Term Potentiation in Models of Alzheimer’s Disease: An Electrophysiological and Proteomic Analysis

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“In this study, we have examined the neuroprotective effects of cannabidiolic acid (CBDA) in models of Alzheimer’s disease (AD).

We used in vitro electrophysiological recording in hippocampal slices and performed proteomic analysis of cortical tissue from APPswe/PS1dE9 (APP/PS1) mice. In wild-type (WT) slices from C57BL6 mice, acute treatment with CBDA (10 μM) did not alter levels of hippocampal long-term potentiation (LTP); however, it did reverse the attenuation of LTP produced by acute beta amyloid peptide (Aβ42). We also examined the effects of CBDA or vehicle in APP/PS1 mice and WT littermates over a 5-week period at 8 months.

LTP levels recorded in slices from WT mice treated with CBDA at 1, 10, or 30 mg/kg (IP) or vehicle were similar. LTP was attenuated in slices from vehicle-treated APP/PS1 compared to vehicle-treated WT mice, while treatment of APP/PS1 mice with all doses of CBDA reversed the deficits in LTP. There was also a deficit in paired-pulse facilitation (PPF) in vehicle-treated APP/PS1 compared to WT, indicating altered synaptic function and transmitter release; this was reversed in slices from CBDA-treated APP/PS1 mice. Levels of cortical soluble Aβ42 were similar across CBDA- and vehicle-treated groups; however, the level of aggregated Aβ42 was decreased in the CBDA-treated group.

Proteomic analysis of cortical tissue from APP/PS1 cortex compared to WT revealed alterations in protein expression, with pathway enrichment analyses suggesting implicated canonical pathways, including mitochondrial dysfunction, protein sorting, and synaptogenesis; all were significantly improved by CBDA treatment. These changes likely facilitate the improvement in synaptic transmission and LTP we observed following CBDA treatment in APP/PS1 mice.

This research suggests that CBDA should be considered a novel therapy for AD.”

https://pubmed.ncbi.nlm.nih.gov/40430085/

https://www.mdpi.com/1422-0067/26/10/4944

Chemical Profiling of Polyphenolic Fraction of Cannabis sativa L. vr. Kompolti Industrial Inflorescences: Insights into Cannabidiol Neuroprotective Effects in a Cellular Model of Parkinson’s Disease

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“The ultra-high-performance liquid chromatography high-resolution mass spectrometry (LC-ESI-HR-MS/MS) technique was used to characterize the polyphenolic fraction of the hot water infusion (WI) of inflorescences of Cannabis sativa L. Kompolti variety, commercially used for food preparations or cosmetic purposes.

On water infusion extract, we applied a multidisciplinary approach, where NMR, MS, in vitro cell-free and cell-based assays coupled with in silico studies, were used to rationalize at the molecular level the effects of the major component Cannabidiol (CBD), in a model of Parkinson’s disease (PD). The phytochemical analysis by LC-MS/MS led to the tentative identification of many components belonging to different classes of polyphenols, such as phenolic acids, flavonoids, and their glycosides. CBD and cannabidiolic acid (CBDA) were also detected in good amounts in the infusion, together with several minor cannabinoids. In addition, the water infusion WI was evaluated for mineral content, total phenolic content, flavonoid content, and antioxidant capacity by DPPH and FRAP methods.

Notably, our results in a cellular model of PD highlight that CBD protects against rotenone-induced cell death without recovering neuronal morphology. These biological outcomes were rationalized by an in silico approach, where we hypothesize that CBD could influence the cellular response to oxidative stress via its interaction with the Keap1/Nrf2 pathway.

In summary, these results enriched the nutraceutical profile of the water infusion of the inflorescences of the Kompolti cultivar, which demonstrated a high CBD content.

This study could lead to the development of dietary supplements that could help in the management of clinical symptoms related to the antioxidant activity of CBD in the pathophysiology of PD, which remains poorly characterized.”

https://pubmed.ncbi.nlm.nih.gov/40431038/

“In summary, this multidisciplinary approach has provided further insight into the human health properties of C. sativa L. Kompolti infusions. When consumed as a beverage as part of a normal diet, the phytoconstituents could provide health benefits through their antioxidant activity in various diseases and would be promising for protection against environmental stresses that contribute to inflammatory processes, cancer, and other degenerative diseases.”

https://www.mdpi.com/2223-7747/14/10/1473