Monthly Archives: April 2025

UK Medical Cannabis Registry: A Clinical Outcomes Analysis for Epilepsy

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“Background: A third of epilepsy patients fail to enter seizure remission despite optimal therapeutic management. Cannabis-based medicinal products (CBMPs) have shown promise as a potential therapy. However, a paucity of high-quality literature regarding CBMPs’ efficacy and safety profile means further investigation is needed. The study aimed to examine changes in epilepsy-specific and general health-related quality of life (HRQoL) patient-reported outcome measures (PROMs) in individuals with treatment-resistant epilepsy.

Methods: A case series of patients with epilepsy from the UK Medical Cannabis Registry analyzed changes in Quality of Life in Epilpesy-31 (QOILE-31), Single-Item Sleep Quality Score (SQS), EQ-5D-5L, Generalized Anxiety Disorder-7 (GAD-7) and Patient Global Impression of Change (PGIC) between baseline, one, three, and six months. Adverse events (AEs) were collected and classified by severity. p < 0.050 was considered statistically significant.

Results: There were 134 patients included. Improvements were recorded from baseline to one, three, and six months in QOILE-31 and all HRQoL PROMs (p < 0.050). Forty patients (29.85%) reported a minimal clinically important difference in Quality of Life in Epilepsy-31 (QOLIE-31) at six months. There were 18 (13.43%) AEs reported by 5 (3.73%) patients, mainly mild and moderate.

Discussion: The proportion of patients achieving a clinically significant change is similar to existing CBMPs in epilepsy literature. AE incidence was lower than similar studies although this may be due to the large proportion (67.16%) of individuals who were not cannabis naïve.

Conclusion: Initiation of CBMPs was associated with an improvement across all PROMs. CBMPs were well tolerated across the cohort. However, randomized controlled trials are needed to help determine causality.”

https://pubmed.ncbi.nlm.nih.gov/40249168/

“Treatment with CBMPs was associated with an improvement in both epilepsy-specific and general HRQoL outcomes at one, three, and six months. This study shows the promising potential of CBMPs as an adjunctive treatment option in the management of TRE.”

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70490

UK medical cannabis registry: an updated clinical outcomes analysis of patients with post-traumatic stress disorder

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“Background: Cannabis-based medicinal products (CBMPs) are a potential treatment for post-traumatic stress disorder (PTSD), but their long-term efficacy and safety need further investigation. This study assessed the changes in health-related quality of life (HRQoL) and adverse events in PTSD patients prescribed CBMPs.

Research design and methods: This observational cohort study included PTSD patients enrolled on the UK Medical Cannabis Registry for 18 months or longer. Changes in PTSD-specific symptoms (IES-R), anxiety (GAD-7), sleep quality (SQS), and general HRQoL (EQ-5D-5 L) were assessed at 1, 3, 6, 12, and 18 months.

Results: In 269 patients, significant improvements in PTSD symptoms, anxiety, sleep quality, and HRQoL were observed at all follow-up points (p < 0.001). On multivariate logistic regression, male gender (OR = 0.51; 95% CI:0.28-0.94; p = 0.034) was associated with a reduced chance of reporting improvements in IES-R. Adverse events were reported by 70 (26.02%) patients, with insomnia (n = 42, 15.61%) and fatigue (n = 40, 14.87%) being the most common.

Conclusions: CBMPs were associated with improvements in PTSD symptoms, anxiety, sleep, and HRQoL at up to 18 months. Although the study’s observational nature limits causal conclusions, these findings support further assessment of medical cannabis.”

https://pubmed.ncbi.nlm.nih.gov/40235073/

“Cannabis-based medicinal products (CBMPs) have emerged as novel treatments for PTSD. This analysis suggests that initiation of CBMP therapy for up to 18 months is associated with improvements in PTSD-specific, HRQoL, anxiety, and sleep symptoms in PTSD patients. Moreover, CBMPs are largely well tolerated across this short-term follow-up.”

https://www.tandfonline.com/doi/full/10.1080/14737175.2025.2490539#abstract

Efficacy and Safety of Cannabinoids for Autism Spectrum Disorder: An Updated Systematic Review

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“Autism Spectrum Disorder (ASD) lacks an established pharmacological treatment protocol, prompting interest in alternative therapeutic approaches, such as cannabidiol (CBD). This systematic review evaluates the potential efficacy and safety of CBD-rich formulations in managing ASD symptoms. A comprehensive search of PubMed, Embase, Scopus, Web of Science, and the Cochrane Library identified seven studies encompassing 494 patients from Brazil and Israel.

Preliminary findings suggest that CBD-rich formulations may provide modest benefits for sleep and social interaction, with a reduction in anxiety symptoms. Regarding core ASD symptoms and behavioral outcomes, cannabinoids demonstrated greater efficacy compared to placebo in some studies. However, adverse events varied, and response to treatment was inconsistent across individuals. While cannabinoids, particularly CBD-rich formulations, appear to be relatively safe and potentially beneficial, further large-scale, controlled trials comparing CBD to established ASD treatments are essential to clarify its role and long-term impact in ASD management.”

https://pubmed.ncbi.nlm.nih.gov/40248548/

https://www.cureus.com/articles/347254-efficacy-and-safety-of-cannabinoids-for-autism-spectrum-disorder-an-updated-systematic-review#!/

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