Cholesterol-induced stimulation of platelet aggregation is prevented by a hempseed-enriched diet

“Hypercholesterolemia indirectly increases the risk for myocardial infarction by enhancing the ability of platelets to aggregate. Diets enriched with polyunsaturated fatty acids (PUFAs) have been shown to reduce the detrimental effects of cholesterol on platelet aggregation.

This study investigated whether dietary hempseed, a rich source of PUFAs, inhibits platelet aggregation under normal and hypercholesterolemic conditions.

Male New Zealand white rabbits were fed one of 6 dietary interventions: regular control diet (RG); control diet + 10% hempseed (HP); control diet + 10% partially delipidated hempseed (DHP); control diet + 0.5% cholesterol (OL); control diet + 0.5% cholesterol + 10% hempseed (OLHP); control diet + 5% coconut oil (CO). After 8 weeks, blood was collected to measure ADP- and collagen-induced platelet aggregation and plasma levels of fatty acids, cholesterol, and triglycerides.

The hempseed-fed animals (HP and OLHP) displayed elevated plasma levels of PUFAs and a prominent enhancement in 18:3n-6 (gamma-linolenic acid, GLA) levels, a unique PUFA found in hempseed. The cholesterol-supplemented groups (OL and OLHP) had significantly elevated plasma levels of cholesterol and triglycerides, but platelet aggregation was significantly augmented only in the OL group.

The addition of hempseed to this diet (OLHP) normalized aggregation. The direct addition of GLA to the OL platelet samples blocked the cholesterol-induced stimulation of platelet aggregation.

The results of this study demonstrate that when hempseed is added to a cholesterol-enriched diet, cholesterol-induced platelet aggregation returns to control levels. This normalization is not due to a reduction in plasma cholesterol levels, but may be partly due to increased levels of plasma GLA.”

https://pubmed.ncbi.nlm.nih.gov/18418423

https://cdnsciencepub.com/doi/10.1139/Y08-011

Cannabis Seed Oil Alleviates Experimental Atherosclerosis by Ameliorating Vascular Inflammation in Apolipoprotein-E-Deficient Mice

“In recent decades, epidemiological, clinical, and experimental studies have demonstrated that a diet with antioxidant or anti-inflammatory function plays a central role in the prevention of atherosclerosis (AS).

The purpose of this study was to explore the effects of Cannabis seed oil (CO) administration on in vitro antioxidant capacity as well as blood lipid profiles, lipid peroxidation, inflammatory response, and endothelial cell integrity. Female ApoE-/- mice were fed a high-cholesterol diet and administrated with CO or phosphate-buffered saline (PBS) and seal oil by gavage for 8 weeks.

The results show that CO administration reduced the levels of serum triglycerides and low-density lipoprotein cholesterol at week 6. Additionally, a decrease in serum tumor necrosis factor α and nitric oxide was also observed. Moreover, results from CD31 staining and scanning electron microscopy revealed that CO treatment alleviated the endothelial cell damage and lipid deposition induced by a high-cholesterol diet. The ratio of lesion area to the total aorta area was 19.57% for the CO group, which was lower than the PBS control group (24.67%).

Collectively, CO exerted anti-atherosclerotic effects by modulating serum lipid profiles and inflammatory responses and improving endothelial cell integrity and arterial lipid deposition. The results provide a promising preventive strategy for the early progression of AS.”

https://pubmed.ncbi.nlm.nih.gov/34037390

https://pubs.acs.org/jafcau/article-abstract/69/32/9102/506931/Cannabis-Seed-Oil-Alleviates-Experimental?redirectedFrom=fulltext

Stability of Cannabinoids in Cannabis: Plant Material, Extracts, Oil Formulations, and Isolates (CBD and Δ9-THC) Under Different Storage Conditions

Background: The chemical stability of cannabinoids in Cannabis sativa plant material and formulated products is a critical factor for quality control, therapeutic efficacy, and regulatory compliance. Cannabinoids such as THC are prone to degradation over time, which is heavily influenced by storage conditions and the product matrix. Despite its importance, comprehensive long-term stability data comparing different plant chemovars (high THC, high cannabidiol [CBD], and intermediate) alongside processed products like extracts and isolates remains limited. This study aims to evaluate the stability of cannabinoids in plant material, extracts, oil formulations, and isolates (CBD and Δ9-THC) under distinct environmental temperatures to optimize storage guidelines.

Methods: Cannabis plant material representing three distinct chemovars-high THC, high CBD, and intermediate (balanced THC/CBD), extracts, pure isolates (THC and CBD) and CBD extract as oil formulation were subjected to extended stability testing over a prolonged period under three controlled temperature environments: room temperature, refrigeration, and freezing. Quantitative analysis of cannabinoid content was performed at regular intervals using gas chromatography (GC/FID) to track degradation and potency over time.

Results: The stability profiles varied depending on the cannabinoid profile, temperature, and matrix type. For the majority of cannabis-derived products, exposure to room temperature accelerated the degradation of THC into cannabinol (CBN), whereas storage at -20°C preserved cannabinoid integrity over the extended timeline. Notably, a distinct divergence was observed between the compounds: CBD-only products demonstrated robust long-term stability even when maintained at room temperature. Conversely, THC-rich matrices were highly susceptible to ambient degradation but exhibited the highest stability when formulated as ethanolic solutions and stored in the freezer (-20°C).

Conclusion: To maximize cannabinoid shelf-life and prevent degradation, storage temperatures must match product composition. While CBD-dominant products can tolerate room-temperature storage, THC-rich products require cold chain management, ideally stored in a freezer at -20°C for optimal long-term potency.”

https://pubmed.ncbi.nlm.nih.gov/42576671

https://journals.sagepub.com/doi/10.1177/25785125261478275

Cannabis-Based Medicinal Products for Endometriosis: A 2-Year Prospective Analysis From the UK Medical Cannabis Registry

Background: Endometriosis affects up to 10% of biological females of reproductive age. Current treatment options are limited and often unsuitable for prolonged use. Cannabis-based medicinal products (CBMPs) have emerged as an alternative for pain management.

Aims: To analyse changes in patient-reported outcome measures (PrOMs), prescribed opioid burden, and the prevalence of adverse events (AEs) in patients prescribed CBMPs for endometriosis-associated pain.

Materials and methods: This was an observational analysis of prospectively collected data from the UK Medical Cannabis Registry. Biological females (≥ 18 years) with a primary diagnosis of endometriosis, enrolled ≥ 2 years prior to data extraction on 06/01/2025, were included. PrOMs and prescribed oral morphine equivalents (OME) were assessed between baseline and 1, 3, 6, 12, 18, and 24 months. Changes from baseline were assessed by repeated-measures ANOVA and Bonferroni-adjusted post hoc pairwise t-tests. p < 0.050 was considered statistically significant.

Results: One hundred and one patients were included. Improvements from baseline were observed in BPI Severity, BPI Interference, SF-MPQ-2 Total, Pain VAS, EQ-5D-5L Index, GAD-7, and SQS at all follow-ups (p < 0.001). Mean prescribed OME decreased from 19.9 ± 17.2 mg/day at baseline to 14.8 ± 15.9 mg/day at 24 months. Eighteen participants (17.8%) reported 165 AEs, of which 84 (50.9%) were mild. The most frequent were fatigue (n = 16; 15.8%), lethargy (n = 15; 14.9%), and headache (n = 13; 12.9%).

Conclusion: CBMP treatment was associated with sustained improvements in pain, health-related quality of life, sleep, and anxiety at 24 months, with a favourable AE profile. Randomised controlled trials are required to establish efficacy and safety.”

https://pubmed.ncbi.nlm.nih.gov/42576801

“Cannabis-based medicinal products (CBMPs) have emerged as an alternative for managing endometriosis-associated chronic pain.

CBMPs include phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), which interact with the endocannabinoid system through cannabinoid receptor type 1 (CB1) and type 2 (CB2).

Anandamide, an endogenous cannabinoid, binds to these receptors to modulate pain. THC is a partial agonist of CB1 and CB2, while CBD increases anandamide by inhibiting its breakdown.”

https://obgyn.onlinelibrary.wiley.com/doi/10.1111/ajo.70173

Cannabidiol attenuates atherosclerosis in male ApoE-/- mice with sex-dependent lipidomic and proteomic remodeling

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid from Cannabis sativa, exhibits anti-inflammatory and antioxidant properties.

We therefore hypothesized that CBD may modulate atherosclerosis development; however, preclinical evidence remains limited and sex-specific effects are poorly understood.

Male and female apolipoprotein E-deficient (ApoE/) mice were fed a Western-type diet for 12 weeks and received either a CBD nanoemulsion (≈80 mg/kg/day) or vehicle via drinking water. Atherosclerosis was quantified by aortic plaque area, and lipidomic profiling together with aortic root proteomics were used to characterize CBD-induced metabolic changes.

CBD treatment significantly reduced aortic plaque area in male but not female mice, without affecting body weight or standard serum lipid parameters.

Untargeted lipidomics revealed sex-specific remodeling of the serum lipidome in males, including enrichment of ether-linked triacylglycerols, a class connected to ether-lipid metabolism; however, no lipid class emerged as a robust correlate of plaque burden. Proteomic analysis identified male-specific downregulation of mitochondrial oxidative and stress-related pathways, consistent with reduced vascular oxidative burden.

In vitro, CBD attenuated oxLDL-induced oxidative stress and inflammatory activation in endothelial cells, supporting a direct vascular effect. CBD elicited no comparable molecular or plaque changes in females.

Collectively, chronic CBD administration exerts a sex-dependent, anti-atherogenic effect in male ApoE-/- mice, associated with downregulation of mitochondrial oxidative metabolism and attenuation of endothelial oxidative and inflammatory activation, alongside remodeling of ether-linked lipid metabolism whose contribution to plaque protection remains to be established.

These findings highlight the importance of incorporating sex-specific responses in future mechanistic and translational studies of CBD in atherosclerosis.”

https://pubmed.ncbi.nlm.nih.gov/42575282

“Cannabinoids are bioactive compounds structurally related to metabolites of dietary essential polyunsaturated fatty acids, collectively termed endocannabinoids. They bind, with variable affinity, to a broad spectrum of endocannabinoid receptors, that contributes to their pleiotropic and sometimes contradictory biological effects.

Cannabinoids are also important modulators of immune function.

Given the central role of inflammation in atherogenesis, modulation of the endocannabinoid system has therefore been proposed as a potential strategy for atherosclerosis prevention and therapy.”

https://www.jlr.org/article/S0022-2275(26)00150-1/fulltext


Cannabidiol as a Promising Anti-Inflammatory Agent Targeting TYK2: Molecular Docking and Dynamic Simulation Approaches for Therapeutic Applications in Multiple Sclerosis

Introduction: Multiple sclerosis (MS) involves chronic inflammation driven by dysregulation of the JAK-STAT pathway. This study aimed to evaluate the potential interaction of natural cannabinoids with TYK2, with a focus on cannabidiol (CBD), using computational in silico approaches.

Methods: A combined molecular docking and molecular dynamics (MD) workflow was used. Cannabinoid ligands and the TYK2 structure (JH2 domain) were prepared and docked in MOE, followed by 20 ns MD simulations under NVT and NPT conditions in GROMACS. Complex stability and ligand-protein interactions were analysed.

Results: CBD showed a competitive docking score (-7.31 kcal/mol) and a refined RMSD of 0.9198 Å. MD simulations revealed a stable CBD-TYK2 complex, with RMSD fluctuations of 0.15-0.20 nm, which were lower than those observed for the reference inhibitor, deucravacitinib. RMSF analysis revealed a slight increase in local flexibility in specific regions without affecting the overall stability of the protein. The radius of gyration remained stable throughout the simulation, indicating that the protein’s compactness was preserved. Hydrogen bond analysis showed fewer but transient interactions for CBD, consistent with a binding mode dominated by hydrophobic interactions.

Discussion: These computational results suggest that CBD interacts stably with TYK2 through a distinct binding mode compared to the reference inhibitor, deucravacitinib, while maintaining the structural integrity of the protein.

Conclusion: CBD showed a stable predicted interaction with TYK2, supporting its potential as a candidate for further in vitro and in vivo studies in the context of MS-related inflammation.”

https://pubmed.ncbi.nlm.nih.gov/42576587

https://www.eurekaselect.com/article/157501

Efficacy of cannabinoids for insomnia and sleep disturbance: A systematic review and meta-analysis of randomized controlled trials

Background: Insomnia is a common sleep disorder that presents with difficulty falling asleep or staying asleep. Standard hypnotics often lead to tolerance and dependency, prompting interest in cannabinoids as alternative sleep aids. This study evaluated the efficacy and safety of cannabinoids in improving sleep among adults with insomnia or poor sleep quality.

Methods: PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science were searched from inception to January 2025 for randomized controlled trials (RCTs) comparing cannabinoids with placebo or melatonin. Primary outcomes were changes in Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). Pooled mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models.

Results: Ten RCTs involving 2134 participants were included. Cannabinoids significantly reduced insomnia severity (MD -3.73; 95% CI -5.04 to -2.42; p < 0.001) and improved sleep quality (MD -3.94; 95% CI -5.47 to -2.40; p < 0.001). Total sleep time increased by 33.99 min (95% CI 20.39 to 47.60), and sleep efficiency improved by 4.31% (95% CI 3.00 to 5.62). Sleep onset latency was modestly reduced (MD -12.0 min; 95% CI -22.6 to -1.4; p = 0.03). Adverse events, mostly mild dizziness and dry mouth, were more frequent with cannabinoids (RR 3.96; 95% CI 1.75 to 9.00), but no serious harms were observed.

Conclusion: Cannabinoids improve sleep quality and duration with acceptable safety, offering a potential alternative for managing insomnia. Larger, long-term trials are warranted to define optimal dosing and sustained efficacy.”

https://pubmed.ncbi.nlm.nih.gov/42574897

“Cannabinoids significantly improved insomnia symptoms and overall sleep quality compared with control treatments.”

“Participants receiving cannabinoids experienced longer sleep duration and better sleep efficiency.”

“Cannabinoid use was associated with faster sleep initiation and improved nighttime sleep continuity.”

https://www.sciencedirect.com/science/article/abs/pii/S1389945726004326?via%3Dihub

Priming Canine Adipose Tissue-Derived Mesenchymal Stem Cells with CBD-Rich Cannabis Extract Modulates Neurotrophic Factors Expression Profile

“The endocannabinoid system regulates key biological functions such as neuroprotection, pain modulation, inflammation, and immunomodulation.

Cannabis-based therapies have gained attention due to the therapeutic potential of their bioactive compounds, particularly phytocannabinoids like cannabidiol (CBD), which exhibit anti-inflammatory, neuroprotective, and immunomodulatory properties.

Mesenchymal stem cells (MSCs) are widely studied for their regenerative and immunomodulatory potential.

This study evaluated the effects of priming canine adipose tissue-derived MSCs (cAT-MSCs) with a CBD-rich cannabis extract on cell morphology, viability, neurotrophic factor gene expression, and cytokine gene and protein expression.

cAT-MSCs (n = 5) were primed for 24 h and divided into three groups: Control (C, unprimed), D1 (2.25 µM CBD), and D2 (225 nM CBD). No morphological or viability changes were observed. Gene expression analysis showed that groups D1 and D2 exhibited increased HGF expression. D1 also showed increased IDO and decreased BDNF expression. In contrast, no significant changes were observed in GDNF, IL-10, TNF-α, IFN-γ, or PTGES2. Regarding the cytokine profile, GM-CSF, IL-2, and IL-10 were undetectable. Notably, IL-8 and MCP-1 levels were significantly reduced in D1 compared to the control.

These findings suggest that CBD priming modulates key regenerative and inflammatory mediators in cAT-MSCs, supporting its potential application in enhancing the efficacy of cell-based therapies.”

https://pubmed.ncbi.nlm.nih.gov/41150065

“Mesenchymal stem cells (MSCs) are used in veterinary medicine for their regenerative, immunomodulatory, and anti-inflammatory properties. Compounds from cannabis, especially cannabidiol (CBD), have shown promising anti-inflammatory and healing effects.

This study evaluated whether a CBD-rich cannabis extract modulates important regenerative and inflammatory factors in MSCs derived from canine adipose tissue. After priming canine adipose tissue-derived MSCs for 24 h, we found no changes in their morphology or viability. However, the priming with CBD-rich cannabis extract has increased the activity of certain genes linked to tissue repair and reduced the levels of inflammatory cytokines.

These results suggest that CBD can influence key factors that help stem cells repair tissue and control inflammation, potentially improving their use in future veterinary therapies.”

https://www.mdpi.com/2306-7381/12/10/926

Delta-9-Tetrahydrocannabinol (∆9-THC) Induce Neurogenesis and Improve Cognitive Performances of Male Sprague Dawley Rats

“Neurogenesis is influenced by various external factors such as enriched environments. Some researchers had postulated that neurogenesis has contributed to the hippocampal learning and memory.

This project was designed to observe the effect of Delta-9-tetrahydrocannabinol (∆9-THC) in cognitive performance that influenced by the neurogenesis.

Different doses of ∆9-THC were used for observing the neurogenesis mechanism occurs in the hippocampus of rats. The brains were stained with antibodies, namely BrdU, glial fibrillary acidic protein (GFAP), nestin, doublecortin (DCX) and class III β-tubulin (TuJ-1). The cognitive test was used novel-object discrimination test (NOD) while the proteins involved, DCX and brain-derived neurotrophic factor (BDNF), were measured.

Throughout this study, ∆9-THC enhanced the markers involved in all stages of neurogenesis mechanism. Simultaneously, the cognitive behaviour of rat also showed improvement in learning and memory functions observed in behavioural test and molecular perspective.

Administration of ∆9-THC was observed to enhance the neurogenesis in the brain, especially in hippocampus thus improved the cognitive function of rats.”

https://pubmed.ncbi.nlm.nih.gov/28933048

“The treatment of 1.5 mg/kg of ∆9-THC has increase all the markers for neurogenesis and cognition function while improve the cognitive performance.”

https://link.springer.com/article/10.1007/s12640-017-9806-x

“Neurogenesis is the scientific term for the birth and growth of new brain cells.”


Cannabidiol confers neuroprotection against 6-OHDA toxicity by rescuing Nrf2 proteostasis and preserving mitochondrial integrity

“Oxidative stress and the progressive degeneration of dopaminergic neurons are key features of Parkinson’s disease (PD). The intrinsically disordered structure of the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which coordinates the main cellular antioxidant response of the body, makes it highly susceptible to misfolding and aggregation under severe oxidative stress, compromising cellular survival.

Cannabidiol (CBD) has potent neuroprotective properties, but its exact molecular mechanism within the dopaminergic redox environment remains unclear. In this study, we investigated the protective effects of CBD against 6-hydroxydopamine (6-OHDA)-induced toxicity in both undifferentiated and mature, post-mitotic differentiated SH-SY5Y cells.

We found that CBD confers robust Nrf2-dependent neuroprotection against 6-OHDA. Importantly, we uncover a previously unexplored mechanism of neuroprotection by which CBD actively prevents the stress-induced sequestration of Nrf2 into insoluble cytoplasmic inclusions under oxidative stress.

We find that CBD keeps Nrf2 in a soluble, functional state, increases Ser40 phosphorylation, restores nuclear localization, and drives the robust transcriptional upregulation of antioxidant enzymes. This targeted activation of Nrf2 effectively reduces intracellular reactive oxygen species (ROS), significantly attenuates mitochondrial fragmentation, and decreases aberrant mitophagic activity.

Overall, our results show that rather than merely scavenging reactive oxygen species, CBD directly increases Nrf2 activity during oxidative stress, enabling a sustained cytoprotective response.

We thus identify CBD as a highly specific, targeted molecule with a high potential for neuroprotective therapy in PD.”

https://pubmed.ncbi.nlm.nih.gov/42570822

“CBD has antioxidant, neuroprotective, anxiolytic, cardioprotective, and anti-inflammatory properties.”

https://www.sciencedirect.com/science/article/pii/S0891584926010105?via%3Dihub