In vitro antibacterial activity of hemp (Cannabis sativa L.) extract seed oil against multidrug resistant bacterial pathogens in small animal veterinary dermatology

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“There is an urgent need for alternative antimicrobial therapies in veterinary small animal dermatology due to the limited therapeutic options available for treatment of infections caused by multidrug-resistant bacteria.

This study aimed to evaluate the potential of hemp (Cannabis sativa L.) seed oil for topical treatment of localized infections of the skin, such as otitis externa.

Antimicrobial activity was determined by broth microdilution using a strain collection of bacterial pathogens associated with skin infections, including Staphylococcus pseudintermedius (n=120), Staphylococcus aureus (n=48), and Pseudomonas aeruginosa (n=26). Checkerboard dilution tests were used to assess the interaction of hemp seed oil with two antimicrobials used for management of otitis externa, gentamicin and enrofloxacin, while in vitro cytotoxicity was evaluated by the cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay on mouse fibroblast cell line L929. Minimum inhibitory concentrations (MICs) in staphylococci (0.025-0.2% v/v) were markedly lower than in P. aeruginosa (>0.4% v/v). Within S. pseudintermedius, methicillin-resistant strains displayed lower susceptibility compared to susceptible strains.

Hemp seed oil showed synergy with gentamicin (Fractional Inhibitory Concentration Index < 0.5), reducing the MIC of gentamicin-resistant S. pseudintermedius strains (≥16µg/ml) below the clinical susceptibility breakpoint (≤4µg/ml). No changes in cell viability were observed at concentrations below 2% v/v.

These findings suggest that hemp seed oil could be an effective and safe alternative or adjuvant to conventional antimicrobials for managing otitis externa and other skin focal infections caused by staphylococci, including methicillin-resistant strains.”

https://pubmed.ncbi.nlm.nih.gov/40513980/

“The findings suggest that hemp seed oil could serve as an effective and safe alternative or adjunct to conventional antimicrobial treatments for localized skin infections, including otitis externa caused by staphylococci, even those resistant to methicillin;”

https://www.sciencedirect.com/science/article/pii/S1090023325000966?via%3Dihub

Nutrients and Bioactive Compounds from Cannabis sativa Seeds: A Review Focused on Omics-Based Investigations

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“Hemp (Cannabis sativa L.) is a versatile crop that can be processed to obtain different products with multiple applications. Its seeds are a well-documented ancient source of proteins, fibers and fats, all of which possess high nutritional value. Additionally, metabolites such as flavones and phenols are present in the seeds, contributing to their antioxidant properties.

Due to hemp seeds’ distinctive nutritional profile, the interest in exploring the potential use in food and nutraceuticals is growing, and they can be considered an interesting and promising alternative resource for human and animal feeding. Omics studies on hemp seeds and their by-products are also being developed, and they contribute to improving our knowledge about the genome, transcriptome, proteome, metabolome/lipidome, and ionome of these sustainable food resources.

This review illustrates the main nutrients and bioactive compounds of hemp seeds and explores the most relevant omics techniques and investigations related to them. It also addresses the various products derived from processing the whole seed, such as oil, dehulled seeds, hulls, flour, cakes, meals, and proteins. Moreover, this work discusses research aimed at elucidating the molecular mechanisms underlying their protein, lipid, fiber, and metabolic profile. The advantages of using omics and multi-omics approaches to highlight the nutritional values of hemp seed by-products are also discussed.

In our opinion, this work represents an excellent starting point for researchers interested in studying hemp seeds as source of nutrients and bioactive compounds from a multi-level molecular perspective.”

https://pubmed.ncbi.nlm.nih.gov/40508032/

“By advancing the understanding and utilization of hemp seeds and their by-products in food, feed, and medical applications, we hope to contribute to positioning hemp as a sustainable and valuable resource for the future.”

https://www.mdpi.com/1422-0067/26/11/5219

Physiological Muscle Function Is Controlled by the Skeletal Endocannabinoid System in Murine Skeletal Muscles

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“The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB1 receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system.

In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration.

Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP).”

https://pubmed.ncbi.nlm.nih.gov/40508098/

“To develop effective therapies for conditions with defective endocannabinoid system (ECS) activity, it is essential to understand the skeletal ECS’s function in health and disease. Here, we present a detailed functional and molecular characterization of a transgenic mouse model with skeletal muscle-specific Cnr1 genetic ablation.

Our in vivo results demonstrate that CB1R knockdown impairs motor coordination and grip strength in mice. Furthermore, at the cellular level, we observed modestly altered calcium homeostasis and significantly decreased mitochondrial function (decreased complex IV activity). Therefore, we propose that the ECS (particularly CB1R) plays a key role in physiological muscle force generation and in maintaining cellular and mitochondrial homeostasis and function.”

https://www.mdpi.com/1422-0067/26/11/5291

Cannabidiol as Modulator of Spontaneous Adipogenesis in Human Adipose-Derived Stem Cells

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“Mesenchymal stem cells isolated from human adipose tissue (hASCs) are a promising tool for tissue repair due to their ability to differentiate into specific cell lineages. The possibility of modulating the adipogenic differentiation of hASCs is crucial in improving their therapeutic potential.

This study aimed to investigate the effects of cannabidiol (CBD), a phytocannabinoid isolated from Cannabis sativa L., on hASCs. Few studies have evaluated its role in stem cell (SC) properties and their differentiation potential.

hASCs were first treated with different concentrations of CBD (ranging from 0.1 to 10 μM) to assess its effects on viability, demonstrating that this molecule is non-toxic, except at the concentration of 10 μM. Subsequently, the role of CBD in the proliferation, metabolism and adipogenic potential of hASCs was analyzed.

CBD promoted adipogenesis in a dose-dependent manner, even in the absence of differentiation medium. This result was evidenced by the presence of lipid vacuoles, the expression of adipogenic markers, cytoskeletal actin rearrangement and modulation in the expression of osteogenic genes.

Although the results indicated a role of CBD in promoting hASC adipogenesis, further research will be needed to explore the mechanism of action of CBD in SC differentiation and to deepen its utility in SC-based approaches.”

https://pubmed.ncbi.nlm.nih.gov/40509260/

“Therefore, as the field of regenerative medicine continues to evolve, the integration of CBD’s properties into therapeutic strategies could hold significant promise in terms of enhancing tissue repair and recovery, offering novel strategies for optimizing healing outcomes and improving patient well-being.”

https://www.mdpi.com/1420-3049/30/11/2367

Single cell multiomic analysis of the impact of Delta-9-tetrahydrocannabinol on HIV infected CD4 T cells

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“Cannabis use is prevalent among individuals living with HIV in the United States, but the impact of cannabis exposure on the reservoir of latently infected cells that persists during antiretroviral therapy (ART) remains unclear. To address this gap, we analyzed the effect of Δ-9-tetrahydrocannabinol (THC) on primary CD4 T cells that were latently infected with HIV.

We found that THC had no detectable effect on baseline or latency reversing agent (LRA) stimulated HIV expression, or on expression of an activation marker (CD38). However, using an integrated multiomic single-cell analysis of genome-wide chromatin accessibility and gene expression, we observed altered expression of several hundred genes in HIV infected CD4 T cells after THC exposure, including transcriptional downregulation of genes involved in protein translation and antiviral pathways, indicating that THC suppresses innate immune activation in infected cells. Additionally, chromatin accessibility analysis demonstrated upregulated chromatin binding activity for the transcriptional regulator CTCF, and reduced activity for members of the ETS transcription factor family in infected cells after THC exposure.

These findings provide insights into the mechanisms by which cannabis use could influence the persistence of HIV within cellular reservoirs and the molecular phenotype of latently infected cells. Further elucidation of the underlying mechanisms involved in THC-mediated changes to HIV infected cells, will lead to an improved understanding of the impact of cannabis use on the HIV reservoir.

Importance: Cannabis use is common among individuals living with HIV, but the long-term effects of cannabis use on the HIV reservoir are not yet studied completely. We employed advanced single-cell technologies to reveal how cannabis components, specifically THC, influence HIV-infected immune cells and their pattern of gene expression. We found that, while THC doesn’t reactivate virus in latently infected cells, it alters the molecular characteristics of these infected immune cells. These findings are important because they underscore how cannabis could regulate persistent infection in people living with HIV. Understanding these cellular changes in response to THC could be helpful for successful treatment for people living with HIV.”

https://pubmed.ncbi.nlm.nih.gov/40502036/

https://www.biorxiv.org/content/10.1101/2025.06.02.657468v1

“Yes, there is growing evidence that cannabis could play a role in regulating persistent HIV infection. Studies suggest that cannabinoids, particularly THC, can alter the molecular characteristics of HIV-infected immune cells without reactivating the virus. These changes might be beneficial in reducing inflammation and improving treatment outcomes for people living with HIV.”

Cannabidiol reverses microglia activation and loss of parvalbumin interneurons and perineuronal nets in a mouse model of schizophrenia

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“Cannabidiol (CBD) has shown potential for treating schizophrenia (SCZ) by targeting its positive and negative cognitive symptoms. In this study, we investigated if CBD could reverse the memory impairment observed after chronic administration of the NMDA receptor antagonist MK-801.

Chronic treatment with MK-801 (0.5 mg/kg i.p., twice a day, for 14 days) resulted in short- and long-term memory deficits and decreased relative power of γ oscillations in freely moving animals. CBD administration (30 mg/kg i.p. daily for seven days after the MK-801 treatment period) reversed these changes. The cognitive effects of CBD were prevented by blocking 5-HT1A but not CB2 receptors.

At the cellular level, the depletion of parvalbumin-positive neurons and their associated perineuronal nets in the prelimbic medial prefrontal cortex (mPFC) and ventral hippocampus (vHip) induced by MK-801 was reversed by CBD. This neuroprotective effect was mediated by 5-HT1A and CB2 receptors in the vHip but was independent of these receptors in the mPFC. Additionally, CBD reversed MK-801-induced microglial activation in both mPFC and vHip, again through 5-HT1A and CB2 receptors.

These findings suggest that CBD modulates multiple pathways affected in SCZ-like conditions, offering a promising therapeutic avenue for SCZ treatment.”

https://pubmed.ncbi.nlm.nih.gov/40484109/

https://www.sciencedirect.com/science/article/abs/pii/S0006899325003336?via%3Dihub

Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments

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“We previously found that enhancing the levels of 2-arachidonoylglycerol (2-AG) and anandamide (AEA) could improve autism spectrum disorder (ASD) symptoms. This study investigated the effect of cannabinoid type 1 receptor (CB1R) in ASD with pharmacological, genetic and brain-targeted intervention and the underlying mechanisms.

Results showed that blocking CB1R counteracted the beneficial effects of boosting 2-AG or AEA on ASD-like behaviors in valproic acid (VPA)-exposed mice. Besides, CB1R knockout mice exhibited ASD-like behaviors and synaptic deficits.

In CB1R-specific brain-targeted regulation, activating CB1R ameliorated synaptic dysfunction, including neuronal complexity, spine density, dendritic integrity, synaptic protein expression, and neuronal damage. Moreover, activating CB1R enhanced the expression and current density of Kir4.1, indicating that CB1R may influence synaptic activity by modulating Kir4.1.

Collectively, our findings indicated a critical role for CB1R in the improvement of ASD-like behavior and synaptic dysfunction, which may offer promising avenues for developing effective treatments for ASD.”

https://pubmed.ncbi.nlm.nih.gov/40484367/

“Brain-specific activation of CB1R improves synaptic impairments in ASD model mice.”

https://www.sciencedirect.com/science/article/abs/pii/S0024320525004321?via%3Dihub

Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy

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“Background: Cancer remains a major global health issue, prompting the need for innovative treatment approaches that extend beyond conventional methods such as chemotherapy and radiation. The endocannabinoid system (ECS), primarily the cannabinoid receptors CB1R and CB2R, presents a promising opportunity for cancer therapy by selectively targeting cell signaling pathways. This systematic review intends to explore the mode of action of synthetic cannabinoids as potential anticancer agents and their impact on tumor growth in various cancer cell lines.

Methods: Of the 287 articles identified between January 1990 and July 2024, 27 studies met strict criteria focusing on their anticancer effects. Data extraction and quality assessment were conducted using GRADE criteria and the Cochrane Risk of Bias tool, ensuring robust evaluation of the studies’ reliability.

Results: Various pharmacological actions of synthetic cannabinoids function as agonists, antagonists, and inverse agonists at the CB1R and CB2R receptors. Key findings indicate that CB2R agonists significantly reduce cancer cell proliferation through diverse mechanisms, with selective CB2R agonists effectively inhibiting cancer cell growth and survival. Studies involving CB1R antagonists, particularly in conjunction with CB2R agonists, highlight their role in blocking CB1R to either validate or enhance the efficacy of CB2R agonists in mitigating tumor growth. Inverse agonists targeting CB2R have shown moderate success in inducing cancer cell death by disrupting survival pathways. Notably, synthetic cannabinoid agonists display significant potential in targeting CB1 and CB2 receptors to inhibit tumor proliferation and promote apoptosis across various cancer types.

Conclusion: The systematic review concludes that CB2R agonists can effectively inhibit tumor growth while inducing apoptosis in various cancers. Although CB1R agonists show potential in modulating cancer pathways, there is a notable lack of research on CB1 inverse agonists, emphasizing the need for further investigation. Additionally, the study advocates for greater exploration of mixed receptor agonist and receptor mode of action to validate these promising therapeutic approaches.”

https://pubmed.ncbi.nlm.nih.gov/40483537/

“Phytocannabinoids, which are the natural cannabinoids found in Cannabis sativa, have been extensively studied for their potential anticancer effects. These compounds act as agonists for cannabinoid receptor 1 and cannabinoid receptor 2, facilitating their therapeutic applications through the activation of these CBRs. By activating CB1R and CB2R, phytocannabinoids produce various therapeutic effects, including anti-nociception, anti-inflammation, anticonvulsant, and anti-emetic properties.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00289-5

Sativex (nabiximols) for the treatment of Agitation & Aggression in Alzheimer’s dementia in UK nursing homes: a randomised, double-blind, placebo-controlled feasibility trial

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“Background: Alzheimer’s Disease (ad) patients often experience clinically significant agitation, leading to distress, increased healthcare costs and earlier institutionalisation. Current treatments have limited efficacy and significant side effects. Cannabinoid-based therapies, such as the nabiximols oral spray (Sativex®; 1:1 delta-9-tetrahydrocannabinol and cannabidiol), offer potential alternatives. We aimed to explore the feasibility and safety of nabiximols as a potential treatment for agitation in ad.

Methods: The ‘Sativex® for Agitation & Aggression in Alzheimer’s Dementia’ (STAND) trial was a randomised, double-blind, placebo-controlled, feasibility study conducted in UK care homes. Participants with probable ad and predefined clinically significant agitation were randomised to receive placebo or nabiximols for 4 weeks on an up-titrated schedule, followed by a 4-week observation period. To be considered feasible, we prespecified the following thresholds that needed to be met: randomising 60 participants within 12 months, achieving a ≥ 75% follow-up rate at 4 weeks, maintaining ≥80% adherence to allocation and estimating a minimum effect size (Cohen’s d ≥ 0.3) on the Cohen-Mansfield Agitation Inventory. This trial is registered with ISRCTN 7163562.

Findings: Between October 2021 and June 2022, 53 candidates were assessed; 29 met eligibility criteria and were randomised. No participants withdrew, and adherence was high (100%) and was generally feasible to deliver. The intervention was well tolerated (0 adverse reactions), with no safety concerns reported.

Interpretation: Despite significant COVID-19 pandemic related challenges, administering nabiximols through oral mucosa to advanced ad patients with agitation demonstrated feasibility and safety. These findings support a larger confirmatory efficacy trial to evaluate the potential therapeutic efficacy of nabiximols for agitation in ad.”

https://pubmed.ncbi.nlm.nih.gov/40479610/

“In conclusion, this study demonstrates the feasibility of a pilot randomised, placebo-controlled trial of nabiximols oral spray for agitation in AD patients in care homes, with no safety concerns observed.”

“Low-dose mixed delta-9-tetrahydrocannabinol and cannabidiol showed favourable safety profile and high tolerability.”

https://academic.oup.com/ageing/article/54/6/afaf149/8158002?login=false

Motor-Related Neural Dynamics are Modulated by Regular Cannabis Use Among People with HIV

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“Recent work has shown that people with HIV (PWH) exhibit deficits in cognitive control and altered brain responses in the underlying cortical networks, and that regular cannabis use has a normalizing effect on these neural responses.

However, the impact of regular cannabis use on the neural oscillatory dynamics underlying motor control deficits in PWH remains less understood. Herein, 102 control cannabis users, control nonusers, PWH who regularly use cannabis, and PWH who do not use cannabis performed a motor control task with and without interference during high-density magnetoencephalography. The resulting neural dynamics were examined using whole-brain, voxel-wise statistical analyses that examined the impact of HIV status, cannabis use, and their interaction on the neural oscillations serving motor control, spontaneous activity during the baseline period, and neurobehavioral relationships.

Our key findings revealed cannabis-by-HIV group interactions in oscillatory gamma within the prefrontal cortices, higher-order motor areas, and other regions, with the non-using PWH typically exhibiting the strongest gamma interference responses. Cannabis-by-HIV interactions were also found for oscillatory beta in the dorsal premotor cortex. Spontaneous gamma during the baseline was elevated in PWH and suppressed in cannabis users in all regions exhibiting interaction effects and the left primary motor cortex, with spontaneous levels being correlated with behavioral performance.

These findings suggest that regular cannabis use has a normalizing effect on the neural oscillations serving motor control and the abnormally elevated spontaneous gamma activity that has been widely replicated in PWH, which may suggest that cannabis has at least some therapeutic utility in PWH.”

https://pubmed.ncbi.nlm.nih.gov/40473990/

“Further, these findings corroborate multiple recent studies showing elevated spontaneous gamma activity in PWH, and that regular cannabis use is associated with a marked suppression in such spontaneous activity.”

https://link.springer.com/article/10.1007/s11481-025-10219-0