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

Beyond Cannabidiol: The Contribution of Cannabis sativa Phytocomplex to Skin Anti-Inflammatory Activity in Human Skin Keratinocytes

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“Background:Cannabis sativa L. (C. sativa) has a long history of medicinal use. Its inflorescences contain bioactive compounds like non-psychotropic cannabidiol (CBD), which is well known for its anti-inflammatory potential in skin conditions such as psoriasis, and psychotropic Δ-9-tetrahydrocannabinol (THC). Keratinocytes, the main cells in the epidermis, are crucial for regulating skin inflammation by producing mediators like IL-8 when stimulated by agents like TNFα. 

Methods: This study explores the anti-inflammatory effects of a standardized C. sativa extract (CSE) with 5% CBD and less than 0.2% THC in human keratinocytes challenged by TNFα. The aim of this study is to analyze the specific contributions of the main constituents of CSE to inflammatory responses in human keratinocytes by fractionating the extract and examining the effects of its individual components. 

Results: MTT assays showed that CSE was non-toxic to HaCaT cells up to 50 μg/mL. CSE inhibited NF-κB activity and reduced IL-8 secretion in a concentration-dependent manner, with mean IC50 values of 28.94 ± 10.40 μg/mL and 20.06 ± 2.78 μg/mL (mean ± SEM), respectively. Fractionation of CSE into four subfractions revealed that the more lipophilic fractions (A and B) were the most effective in inhibiting NF-κB, indicating that cannabinoids and cannflavins are key contributors. Pure CBD is one of the most active cannabinoids in reducing NF-κB-driven transcription (together with THC and cannabigerol), and due to its abundance in CSE, it is primarily responsible for the anti-inflammatory activity. 

Conclusions: This study highlights CBD’s significant role in reducing inflammation in human keratinocytes and underscores the need to consider the synergistic interactions of several molecules within C. sativa extracts for maximum efficacy. Standardized extracts are essential for reproducible results due to the variability in responses.”

https://pubmed.ncbi.nlm.nih.gov/40430467/

“In conclusion, the results of this study on CSE underscore the significant role of CBD in exerting anti-inflammatory effects in human keratinocytes.”

https://www.mdpi.com/1424-8247/18/5/647

Cannabidiol dose dependently reduces alcohol intake in mice via a non-5-HT1A receptor mechanism: Exploration of other potential receptor targets

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“Background and purpose: Binge drinking is a risky pattern of alcohol intake and a major predictor of alcohol use disorder (AUD). Current AUD medications have limited efficacy and poor patient compliance, calling for more effective therapeutics. Cannabidiol (CBD), a non-intoxicating component of cannabis, has emerged as a potential novel therapeutic. However, receptor mechanisms in CBD’s alcohol-related effects have not been investigated comprehensively.

Experimental approach: Using the murine drinking-in-the-dark model of binge drinking, our research aimed to confirm a reduction of alcohol consumption with CBD (7.5, 15, 30, 60, 120 mg kg-1) in male and female mice. Behavioural pharmacological approaches were used to explore CBD interactions with identified target mechanisms: serotonin-1A receptor (5-HT1AR) and peroxisome proliferator-activated receptor-gamma (PPARɣ), and the novel targets, chemokine receptor type-4 (CXCR4) and neuropeptide S receptor (NPSR).

Key results: Acute CBD dose dependently suppressed binge-like drinking and blood ethanol concentration. The effect was not driven by locomotor impairments and was maintained across sub-chronic treatment. Blockade of 5-HT1AR and PPARɣ had no impact on CBD’s reduction of alcohol consumption. Co-administration of subthreshold CBD doses and a NPSR antagonist implicated NPSR blockade as a potential mechanism contributing to CBD’s effect, whereas co-administration of CBD and a CXCR4 antagonist suggested CXCR4 was not involved. However, the potent and selective CXCR4 antagonist AMD3100 reduced ethanol consumption.

Conclusions and implications: CBD represents a promising candidate to reduce voluntary alcohol consumption. Mechanisms driving CBD’s alcohol-related effects remain unclear and may involve polypharmacology, including actions at the NPSR identified in the present study.”

https://pubmed.ncbi.nlm.nih.gov/40432283/

“These experiments consistently showed a dose-dependent suppression of alcohol consumption by CBD.”

https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70070

Proteomic Analysis of Invasive Breast Cancer Cells Treated with CBD Reveals Proteins Associated with the Reversal of Their Epithelial-Mesenchymal Transition Induced by IL-1β

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“Cannabidiol (CBD) has shown promise in treating cancers with an inflammatory microenvironment.

Although it has been demonstrated that IL-1β induces epithelial-mesenchymal transition (EMT) of MCF-7 cells and CBD reverts this process, in restoring the epithelial non-invasive phenotype, there is limited understanding of how this cannabinoid regulates these processes.

In this work, MCF-7 cells were induced to adopt an aggressive phenotype (6D cells), which was reversed by CBD.

Then, protein expression was analyzed by mass spectrometry to compare 6D vs. MCF-7 cells and 6D+CBD vs. 6D cells proteomes. Novel proteins associated with EMT and CBD signaling were identified. Twenty-four of them were oppositely regulated by IL-1β and CBD, suggesting new points of crosstalk between the IL-1β and CBD signaling pathways.

From the data, two protein networks were constructed: one related to EMT with 58 up-regulated proteins and another with 21 related to CBD signaling. The first one showed the proteins BRCA1, MSN, and CORO1A as the key axis that contributes to the establishment of a mesenchymal phenotype. In the CBD signaling, the key axis was formed by SUPT16H, SETD2, and H2BC12, which suggests epigenetic regulation by CBD in the restoration of an epithelial phenotype of breast cancer cells, providing new targets for anticancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/40429863/

“All these results provide new important insights that could help to understand how CBD counteracts the effects of IL-1β and the restoration of the epithelial phenotype as a possible control of cancer progression.”

https://www.mdpi.com/1422-0067/26/10/4721

The Anticonvulsant Effects of Different Cannabis Extracts in a Zebrafish Model of Epilepsy

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“Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects.

One promising alternative is pure cannabidiol (CBD), but using a whole cannabis extract may be equally effective and preferred for some patients.

In the current study, we employed the pentylenetetrazole (PTZ)-induced hyperactivity model in zebrafish to compare the effects of CBD with various cannabis extracts. We evaluated three cannabis strains, each subjected to three different extraction methods, and benchmarked the results against the commercially available AED valproic acid (VPA).

Our findings revealed that 5.7 µg/mL of CBD and 10 µg/mL of different extracts significantly reduced movement compared to PTZ and VPA. In addition, effective extracts produced effects similar to pure CBD despite containing much lower molecule levels.

These results reinforced and expanded previous evidence supporting the clinical potential of both CBD and whole cannabis extracts for seizure control while suggesting a possible entourage effect. Further research is necessary to determine which patients may benefit more from pure CBD versus those who might prefer whole cannabis extracts.”

https://pubmed.ncbi.nlm.nih.gov/40427547/

“In conclusion, our results validate and extend previous ones concerning the potential clinical effects of both CBD and whole cannabis extracts used for seizure control.”

https://www.mdpi.com/2218-273X/15/5/654