Category Archives: Uncategorized

Evaluation of long-term safety profile of an EU-GMP certified Cannabis sativa L. strain in a naturally aging preclinical model

Posted on by

“Aging is characterized in part by chronic, low-grade inflammation, a major driver of cognitive decline, metabolic imbalance and organ dysfunction. Despite its central role in age-related morbidity, pharmacological strategies with well-defined long-term safety profiles remain limited.

Phytocannabinoids have been proposed as modulators of neuroinflammatory and metabolic pathways, but their chronic safety during natural aging is poorly characterized.

Our team has previously reported the acute and 28-day repeated-dose toxicity profile of an EU-GMP certified Cannabis sativa L. strain (Cannabixir® Medium Flos). Here, we extend this work by assessing its long-term safety in a naturally aging preclinical model. Mature to older mice received chronic, intermittent administration of Cannabixir® Medium Flos (2.5, 5, and 10 mg/kg), defined as daily weekday dosing for 3 or 6 months. Clinical and histopathological evaluations were conducted with a focus on systemic and central nervous system safety.

Chronic administration was well tolerated across all doses and durations.

Body weight remained stable despite increased food intake. Respiratory quotient values were preserved and close to 1 across all groups. Histological analyses confirmed preserved neuronal and glial architecture with no evidence of central nervous system injury or other organ-level toxicity. Long-term, intermittent Cannabixir® Medium Flos administration was well tolerated in naturally aged mice, with no adverse effects on systemic physiology or central nervous system integrity.

Together with prior acute and sub-chronic toxicity data, these findings provide robust evidence supporting the long-term safety of EU-GMP certified Cannabis sativa L. strain in the context of aging.”

https://pubmed.ncbi.nlm.nih.gov/41357885

“Importantly, the endocannabinoid system itself undergoes profound remodeling with aging, including reduced endocannabinoid tone, altered receptor expression and impaired signaling efficiency, changes that correlate with increased vulnerability to inflammation, metabolic imbalance, and neurodegeneration. These age-related alterations highlight the importance of evaluating the long-term safety of cannabinoid-based interventions in naturally aging bodies.”

“These findings suggest the potential for phytocannabinoid-mediated neuroprotection via modulation of the endocannabinoid system, although the precise molecular pathways remain to be elucidated.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1716366/full

Evaluation of two different Cannabis sativa L. extracts as antioxidant and neuroprotective agents

Posted on by

“Cannabis sativa L. is a plant that contains numerous chemically active compounds including cannabinoids such as trans-Δ-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and flavone derivatives, such as luteolin-7-O-glucuronide and apigenin glucuronide.”

“These extracts could be a source of compounds with potential benefit on human health, especially related to neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/36176449

“In conclusion, this study provided new insights into the biological activities of two different extracts of C. sativa. It was revealed that these extracts constitute a valuable and interesting natural source of bioactive molecules with great antioxidant properties, potentially capable of preventing neurodegenerative diseases.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.1009868/full

 

Characterization and antifungal properties against Botrytis cinerea of bacteria isolated from hemp seed oil

Posted on by

“Botrytis cinerea is a pathogen infecting Cannabis sativa L. plants, causing economic losses, and can develop resistance to chemical fungicides, the use of which is restricted in cannabis production. Thus, developing biocontrol methods is imperative.

Seven bacterial strains were isolated from hemp seed oil, characterized, and examined for the potential to control a B. cinerea isolate from cannabis.

Three isolates, Bacillus mojavensis HOB3, Paenibacillus sp. HOB6 and Bacillus subtilis HOB7 exhibited significant inhibition of B. cinerea. These isolates were further evaluated for their biosurfactant activity using two liquid media, Lysogeny Broth (LB) and hydrocarbon-amended Bushnell and Haas (BH). The oil-spreading and drop-collapse assays revealed growth-medium-dependent variation in surface activity associated with biosurfactant presence. The BH cell-free extract (BH-CFE) of B. subtilis HOB7 showed the highest estimated biosurfactant presence and antifungal activity against B. cinerea, but both activities were absent when using the LB cell-free extract (LB-CFE) of B. subtilis HOB7.

Thus, a potential relationship between antifungal activity and biosurfactant production was suggested. Genome mining of the strains identified gene clusters encoding compounds with antifungal activity, including the biosurfactants polymyxin B, fusaricidin B, fengycin, and surfactin.

To our knowledge, this is the first report of the isolation of hemp seed oil bacteria with potential biocontrol properties against fungal phytopathogens.”

https://pubmed.ncbi.nlm.nih.gov/41349011

https://cdnsciencepub.com/doi/10.1139/cjm-2025-0241

“Polymyxin B, fusaricidin B, fengycin, and surfactin are all natural lipopeptides (or cyclic non-ribosomal peptides) produced by bacteria of the Paenibacillus and Bacillus genera. They act as biosurfactants and have various antimicrobial properties, particularly as antibiotics and fungicides.” 

Computational GWAS Meta Meta Analysis Revealing Cross Talk Between Cannabis CNR1 and DRD2 Receptors Optimizing Long-Term Outcomes for Cannabis Use Disorder (CUD) By Enhancing Dopamine Homeostasis Promoting High-Quality Cannabis Medicinals

Posted on by

“This paper presents a shared perspective from scientists and clinicians seeking to harness the therapeutic potential of cannabis while addressing Cannabis Use Disorder (CUD) through reproducible scientific findings.

Rather than blocking CNR1 receptors, which may induce hypodopaminergia, we propose a pro-dopaminergic strategy using a natural nutraceutical formulation designed to enhance dopamine release and upregulate D2 receptor mRNA, thereby increasing D2 receptor density.

Given the failure of CNR1 antagonists such as Rimonabant, we argue for an opposite approach: restoring dopamine balance through CNR1 stimulation rather than inhibition.”

https://pubmed.ncbi.nlm.nih.gov/41333412

https://www.researchsquare.com/article/rs-8140327/v1


Supercritical CO2 extraction of hemp seeds: A multivariate perspective on the influence of processing parameters on oil composition, antioxidant activity, and enzyme inhibition

Posted on by

“Hemp seeds are valued for their unique nutritional and health benefits.

This study examined the impact of supercritical (sc)CO2 extraction conditions on hemp seed oil yield, composition, antioxidant activity, and enzyme inhibition using a multivariate approach. While pressure (300-500 bar) had minimal effects, temperature (40-60 °C) and ethanol addition (0.6-1.5 %) significantly influenced oil yield.

The levels of fatty acids, tocopherols, carotenoids, chlorophylls, phenolics, and flavonoids varied independently of extraction pressure and temperature, but their extractability generally increased with ethanol concentration. The co-solvent addition also enhanced radical scavenging activity but diminished the metal-reducing and chelating properties.

Hemp seed oils inhibited enzymes linked to chronic diseases like diabetes, skin disorders, and Alzheimer’s.

Multivariate analysis grouped samples by fatty acid profile, pigment content, and bioactivity. This work provides novel insights into how scCO2 conditions affect the chemical and biological properties of hemp seed oils.”

https://pubmed.ncbi.nlm.nih.gov/41341704

“Cannabis sativa L. (hemp) seeds have been consumed as animal feed or for human nutrition for thousands of years. The whole hemp seeds are comprised of fiber, proteins, and contain more than 30 % oil.

Hemp seed oil is abundant in polyunsaturated fatty acids (PUFAs) and exhibits a favorable omega-6 to omega-3 fatty acid (ω6/ω3) ratio of 3:1. This ratio is regarded as optimal in human nutrition, as it can significantly reduce the incidence of cardiovascular pathologies.”

“This study highlighted that scCO2 extraction is a promising method for obtaining high-quality oil from de-hulled hemp seeds, with tunable parameters influencing both yield and bioactivity.”

https://www.sciencedirect.com/science/article/pii/S2590157525011435?via%3Dihub

A single dose of cannabidiol modulates the relationship between hippocampal glutamate and learning-related prefrontal activation in individuals at Clinical High Risk of Psychosis

Posted on by

“Background: Cannabidiol (CBD) is being studied as a potential intervention for the people at clinical high risk for psychosis (CHR), though the mechanisms underlying its effects are not fully understood. Previous studies indicate that a single dose of CBD can normalize alterations in memory-related brain activation and modulate hippocampal glutamate levels in the early stages of psychosis. This study aimed to examine the acute effects of CBD on the relationship between hippocampal glutamate levels and brain activation during verbal memory in individuals at CHR.

Methods: A total of thirty-three participants (n = 33) at CHR were randomly assigned to receive a single 600 mg dose of CBD (CHR-CBD) or a placebo capsule (CHR-PLB). Age-matched healthy controls (HC) (n = 19) received no study drugs. Participants underwent MRI scanning while performing a verbal learning task, and proton magnetic resonance spectroscopy to measure hippocampal glutamate levels. Effect of group x hippocampal glutamate interactions on brain activation was tested.

Results: CHR-PLB showed positive correlation between hippocampal glutamate levels and dorsolateral prefrontal cortex (dlPFC) (Pcorr. = 0.0039) activation compared to HC during both verbal encoding and recall. Under a single dose of CBD, the glutamate-dlPFC activation relationship was negative and significantly different compared to placebo in CHR individuals (Pcorr. = 0.0001) during both verbal encoding and recall. The reversed correlation in CBD group was also observed in the parahippocampal gyrus (Pcorr. = 0.0022) and amygdala (Pcorr. = 0.0019) during verbal recall.

Conclusions: These findings suggest that CBD may normalise disrupted hippocampal-prefrontal glutamatergic coupling in CHR, highlighting its potential to target the neurochemical mechanisms underlying cognitive impairment.”

https://pubmed.ncbi.nlm.nih.gov/41337954

“To the best of our knowledge, this is the first study to demonstrate that a single dose of CBD may partially attenuate the altered relationship between hippocampal glutamate levels and activation in the prefrontal cortex, amygdala, and parahippocampal regions in individuals at CHR.”

“Single dose of CBD modulates hippocampal glutamate-prefrontal activation coupling in CHR.”

https://www.sciencedirect.com/science/article/abs/pii/S0925492725001507?via%3Dihub

Medicinal use of non-prescribed cannabis: a cross-sectional survey on patterns of use, motives for use, and treatment access in the Netherlands

Posted on by

“Background: Despite the Netherlands having one of the world’s oldest medical cannabis programs, the majority of people who use cannabis for medicinal purposes continue to rely on non-prescribed sources. This study investigates patterns of use, motives for use, perceived effectiveness, and barriers to accessing prescribed cannabis among individuals self-medicating with non-prescribed cannabis.

Methods: A cross-sectional online survey was conducted between January and April 2023, using convenience sampling primarily via social media. Participants (N = 1059) were adults (18 years or older) residing in the Netherlands who self-reported current use of non-prescribed cannabis-based products to manage physical or mental health symptoms.

Results: Cannabis was used to manage a wide range of conditions, most commonly chronic pain, sleep disorders, depression, and ADHD/ADD, with three out of four participants reporting use for multiple conditions. Most participants obtained cannabis from coffeeshops, although one in four also reported home cultivation as a source. Participants typically smoked cannabis with tobacco, reported (near-)daily use for therapeutic purposes, and indicated a monthly expenditure of €100. The majority was not aware of the THC and CBD content of their products. Perceived effectiveness was rated as high, and more than half of those with a history of prescription medication use reported substituting cannabis for these medications. Only a minority of participants had ever used, or were currently using, prescribed cannabis. Commonly cited barriers included perceived lower quality, higher cost, and lower ease of access compared with non-prescribed cannabis.

Conclusions: The widespread use of non-prescribed cannabis for medicinal purposes in the Netherlands reflects both unmet health needs and barriers within the regulated medical cannabis system. Risky use practices – such as smoking cannabis with tobacco and using products without knowing their cannabinoid content – raise public health concerns. The findings highlight the need for harm reduction strategies and policies that better align medical cannabis regulation with patients’ real-world behaviours and care needs.”

https://pubmed.ncbi.nlm.nih.gov/41331499

https://link.springer.com/article/10.1186/s42238-025-00355-y

The endocannabinoid system as a therapeutic target in prodromal psychosis: From molecular mechanisms to clinical applications

Posted on by

“This systematic review explores the role of the endocannabinoid system (ECS) in prodromal psychosis and its potential as a therapeutic target.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 22 studies published between 2000 and 2025 were analyzed, comprising preclinical research, genetic studies, neuroimaging investigations, and clinical trials.

Converging evidence suggests that ECS alterations precede and potentially contribute to the development of psychotic symptoms, with CB1 receptor modifications and endocannabinoid levels correlating with symptom severity and transition risk to full-blown psychosis.

Neuroimaging studies revealed reduced CB1 receptor availability in key brain regions in high-risk subjects, and intervention studies, particularly with cannabidiol-though its therapeutic mechanisms likely extend beyond ECS modulation to include dopaminergic and other neurotransmitter pathways-have shown promising results.

Proposed mechanisms of action include stress response attenuation, neuroinflammatory modulation, neurodevelopmental stabilization, and normalization of the dopamine-glutamate interface.

Despite limitations of existing studies, primarily small size and short duration, this review provides a solid foundation for developing ECS-targeted interventions as a promising approach to modify disease trajectory during the prodromal phase, potentially offering safer and more effective therapeutic options for individuals at clinical high risk for psychosis.”

https://pubmed.ncbi.nlm.nih.gov/41328544

https://journals.sagepub.com/doi/10.1177/02698811251389574

RSM-Based Optimization of Dose Response and Antibacterial Potential of Cannabis sativa (L.) Leaves Using Computational Analysis

Posted on by

“Background: In light of the growing problem of antibiotic resistance, it is imperative to investigate new sources, and plants offer a promising supply of bioactive chemicals. Because of its numerous uses in industry, health, and nutrition as well as its antibacterial qualities, Cannabis sativa (C.sativa) has garnered a lot of study interest. This study sought to determine whether ethanolic extracts from C.sativa leaves have antibacterial properties against six human pathogenic microorganisms.

Methodology: The antibacterial activity of C.sativa ethanolic extract was tested against six bacteria according to design of experiments made by Agar diffusion method accompanied by response surface method (RSM) of Minitab 17 software. The different combinations set were, concentration: 5.0, 7.5, and 10.0, pH: 5.0, 6.5, 8.0 and temperature: 35°C, 37.5°C, 40°C. By using RSM, maximum antibacterial activity has been checked for ethanolic extract of C.sativa against six bacteria by choosing three independent variables, temperature, pH, and concentration. In in-Silico studies, homology, threading approach, structure prediction, ligands designing and docking studies was performed against the antimicrobial target sequences for Beta-Lactamase, GABA Receptor, Lipoteichoic Acid, N-Acetylglucosamine (NAG), Peptidoglycan and Topoisomerase-IV through FASTA format from UniProt for structure prediction.

Results: The results indicated that the three concentrations were effective against tested bacteria. Moreover, effect of pH caused a significant variation in zone of inhibition. The graphs presented in this study indicate the highest zone of inhibition for plant extract; have been achieved at concentration of 10.0, pH 5.1 and temperature 37.5°C. It shows that by keeping the pH low, antibacterial activity will increase. Through the multiple regression analysis on the experimental data, the fitted regression model for the response variable and the test variable x1, x2, x3 are correlated by the second order polymeric equation.

Conclusion: It has been concluded that C.sativa can be considered as an effective drug in curing diseases caused by bacteria. Using the optimized values of temperature and pH analyzed in this experiment.”

https://pubmed.ncbi.nlm.nih.gov/41324030

“Humans have been employing C.sativa since ancient times, and numerous historians have recorded multiple uses of this plant abroad. This plant has been cultivated for religious and recreational purposes, as well as for food, fiber, and oil, according to recorded history. C.sativa is also used therapeutically to treat depression, inflammation, and chronic pain, according to numerous ethnobotanical surveys.”

“This study is the continuation of the research to examine the effectiveness of ethanolic extracts made from C. sativa leaves against harmful microorganisms in humans. The results show that this extract has strong antibacterial activity against a variety of pathogens, such as Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli, Bacillus subtilis, Staphylococcus typhi, and Staphylococcus aureus which is affected more strongly by the pH and temperature variations rather than the concentrations of the extract. Moreover, it is confirmed by the application of the RSM model which indicates its activity. The zones of inhibition produced in the repetitive study has been concluded that C. sativa may be qualified as the drug of the future that can be efficacious for combating bacterial infections. The said plant is of high importance to synthesize a very high potency antibacterial drug by using the optimized ranges of temperature and pH.”

https://journals.sagepub.com/doi/10.1177/15593258251404067

Cannabis Use in Central Disorders of Hypersomnolence in the Netherlands

Posted on by

“Introduction: The endocannabinoid system plays a role in sleep-wake regulation. In clinical practice, people with central disorders of hypersomnolence (CDH) frequently report use of cannabis.

Methods: We compared lifetime and current use of cannabis of people with CDH to the Dutch general population. Additionally, we assessed cannabis use in relation to hypersomnolence symptoms.

Results: In total, 76 (out of 88) patients completed the online questionnaire. Lifetime cannabis use (42% vs. 23%, p < 0.001) and current use (18% vs. 4%, p < 0.001) were higher in people with CDH compared to the Dutch general population. For 57% of patients currently using cannabis, improvements of at least one CDH symptom were the motivation for use. Additionally, 79% of current cannabis users reported cannabis-related effects on a symptom, which were mostly positive (43%), some negative (7%), or mixed effects (29%). Patients that stopped using mostly started using cannabis before symptom onset and for recreational purposes. The most reported reasons to stop using were disadvantages of using or changes in the social environment.

Conclusion: This study provides a rationale for future research on the potential benefits of cannabis in CDH.”

https://pubmed.ncbi.nlm.nih.gov/41321442

https://karger.com/mca/article/8/1/181/935204/Cannabis-Use-in-Central-Disorders-of