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Cannabis sativa chemotypes modulate TLR-associated innate immune gene expression and reduce BoAHV-1 replication in bovine cells

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“Cannabis sativa L. produces a wide range of bioactive metabolites, including phytocannabinoids such as tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabigerol (CBG), which exhibit antiviral activity and modulate innate immune responses through Toll-like receptors (TLRs), particularly TLR4 and TLR7. The cross-regulation between cannabinoids and TLRs can influence the production of cytokines and antimicrobial peptides.

Given their key role in orchestrating innate immunity, particularly inflammatory responses and antiviral activity, understanding these processes in bovine immune cells is essential.

This study evaluated the immunomodulatory and antiviral effects of extracts from C. sativa chemotypes – THC-dominant (I), intermediate THC:CBD (II), CBD-dominant (III) and CBG-dominant (IV) – in bovine cells.

In peripheral blood mononuclear cells, chemotype I induced an enhanced inflammatory response, increasing TLR4 and BMAP28 transcription and pro-inflammatory cytokine expression at both transcriptional and protein levels. Similarly, chemotype IV promoted a pro-inflammatory profile characterised by increased TLR4, BMAP28 and IFNβ expression, as well as elevated TNFα protein levels.

In contrast, chemotypes II and III elicited anti-inflammatory effects. Chemotype III decreased TLR4, TLR7, BMAP28, TNFα and IFNβ transcription, although IFNγ protein levels increased. Chemotype II produced a comparable, although less pronounced, anti-inflammatory pattern, reducing TLR4, TLR7, TNFα and IFNβ while increasing BMAP28. Additionally, chemotypes II, III, and IV exhibited antiviral activity in BoAHV-1-infected MDBK cells, significantly reducing viral titres at 48 h post-infection.

Overall, these findings demonstrate that C. sativa chemotypes differentially modulate bovine innate immune gene expression and may also exert antiviral effects, highlighting their potential as dual immunomodulatory and antiviral agents in bovine infectious contexts.”

https://pubmed.ncbi.nlm.nih.gov/42561569

“Cannabis sativa L. (Cannabaceae) produces diverse chemically active compounds, with cannabinoids being the most studied class due to their biological and therapeutic potential.”

https://www.sciencedirect.com/science/article/abs/pii/S0161589026001768?via%3Dihub


Real-world quality of life and sleep outcomes in patients treated with THC- and CBD-rich Cannabis oil: a cross-sectional study

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“The endocannabinoid system plays an important role in the modulation of pain, mood, sleep, and subjective wellbeing. Despite the growing clinical use of medicinal Cannabis, real-world data simultaneously evaluating quality of life and sleep-related outcomes in heterogeneous clinical populations remain limited.

This study aimed to assess quality of life and sleep satisfaction in patients using medical Cannabis oil under supervised clinical follow-up. This cross-sectional observational study included patients treated with full-spectrum medical Cannabis oil rich in tetrahydrocannabinol (THC) and cannabidiol (CBD) in a real-world clinical setting.

Quality of life was assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Sociodemographic, clinical, and treatment-related data were collected via an electronic questionnaire. Nonparametric analyses, Spearman correlation, and ordinal logistic regression models were performed. Seventy-one participants were included, predominantly female, with diverse clinical conditions.

Participants reported generally favorable perceptions regarding quality of life and sleep satisfaction, with median scores concentrated in the higher response categories. Positive correlations were observed between the psychological domains of quality of life and sleep satisfaction.

Higher Cannabis oil concentrations and longer treatment duration were associated with higher odds of better outcomes.

In a real-world clinical context, supervised use of full-spectrum medical Cannabis oil was associated with favorable patient-reported perceptions of quality of life and sleep, consistent with perceived effectiveness.

These findings highlight the need for longitudinal studies with pre-treatment baseline assessment.”

https://pubmed.ncbi.nlm.nih.gov/42558508

“Cannabis sativa L. [Cannabaceae] has a documented history of medicinal use spanning thousands of years across diverse cultural and geographic contexts, with traditional applications encompassing pain relief, mood modulation, sleep induction, and the management of inflammatory and neurological conditions.”

“The growing integration of Cannabis into contemporary clinical practice reflects both the long-standing ethnopharmacological tradition associated with this species and the expanding body of evidence supporting the pharmacological activity of its principal phytocannabinoid metabolites, tetrahydrocannabinol (THC) and cannabidiol (CBD).”

“In summary, the results suggest that, in supervised clinical practice, patients using full-spectrum THC and CBD rich oil reported favorable perceived quality of life and sleep satisfaction.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1862725/full


Cannabidiol selectively attenuates lipotoxic immunometabolic inflammation in human macrophages

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“The role of saturated fatty acid-induced immunometabolic stress in macrophage dysfunction during metabolic disease remains incompletely understood, particularly the interplay between inflammatory signaling and intracellular lipid handling.

We employed a tightly controlled palmitic acid (PA)-based lipotoxicity model in PMA-differentiated U937-derived human macrophage-like cells to investigate how lipid excess reshapes inflammatory responses and to evaluate the modulatory effects of cannabidiol (CBD).

PA exposure induced a metabolically stressed yet viable macrophage phenotype, characterized by a broad cytokine remodeling profile. This included induction of classical proinflammatory cytokines such as interleukin (IL)-6, together with activation of inflammasome-associated cytokines IL-1β and IL-18 and additional immunoregulatory mediators, while tumor necrosis factor alpha (TNF-α) contributed to the overall inflammatory profile in a multivariate analysis. These changes were accompanied by a significant, time-dependent storage of intracellular triglycerides (TG) consistent with lipid overload and altered lipid handling.

CBD co-treatment did not compromise cell viability but selectively attenuated PA-induced inflammatory response in a cytokine-dependent manner, with the most significant reduction observed at higher concentrations. In parallel, CBD significantly reduced intracellular TG accumulation under lipotoxic conditions.

Collectively, these findings define a lipotoxicity-associated macrophage phenotype driven by saturated fatty acids and identify CBD as a context-dependent modulator of immunometabolic inflammation.

This work provides a controlled experimental framework to study lipid-driven inflammatory dysfunction and supports the potential of CBD as a targeted strategy to modulate metabolic inflammation without broadly suppressing immune function.”

https://pubmed.ncbi.nlm.nih.gov/42534637

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential regulator of inflammatory and metabolic processes. Unlike traditional anti-inflammatory drugs, CBD exerts context-dependent immunomodulatory effects across multiple experimental systems, encompassing both immune and metabolic cells.”

“Overall, this work supports CBD as a context-dependent modulator of immunometabolism response in PMA-differentiated U937-derived macrophages and provides a controlled experimental framework for studying lipid-driven inflammatory dysfunction in U937-derived macrophages.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1873494/full

Cannabidiol-Dominant Cannabis sativa L. Inflorescence Extract Ameliorates Atopic Dermatitis by Modulating NLRP3 Inflammasome and JAK1/STAT6 Signaling in DNCB-Induced Mice

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“Background/objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disorder requiring sustainable therapeutic alternatives. Cannabis sativa L. is a valuable industrial crop rich in bioactive secondary metabolites; its potential as a standardized functional ingredient for promoting skin health has not yet been fully investigated. This study aimed to evaluate the therapeutic effects of a chemically characterized C. sativa inflorescence ethanol extract (CSE) on AD.

Methods: To evaluate the efficacy of CSE, phytochemical profiling was performed using UPLC, and its underlying molecular mechanisms were investigated in a DNCB-induced mouse model.

Results: UPLC analysis was employed to establish the phytochemical profile, identifying 15 cannabinoids and quantifying 8 major components. CBDA was the most abundant component, with a content of 261.79 mg/g in the extract. In a DNCB-induced mouse model, CSE significantly reduced mast cell infiltration and serum IgE levels while downregulating Th2-associated cytokines. At the molecular level, CSE inhibited the activation of the MAPK, NLRP3 inflammasome, and JAK1/STAT6 signaling pathways. Crucially, CSE treatment substantially increased the expression of skin barrier proteins, such as filaggrin and involucrin, thereby enhancing skin hydration.

Conclusions: These findings suggest CSE as a high-value functional ingredient capable of ameliorating AD by modulating multi-target immune responses. This study provides a robust scientific basis for utilizing standardized C. sativa inflorescence as a potent functional ingredient or a nutraceutical agent for the management of chronic skin inflammatory conditions.”

https://pubmed.ncbi.nlm.nih.gov/42514451

“In conclusion, this study provides a comprehensive scientific basis for the use of CSE by demonstrating its multi-target modulation of inflammatory pathways, specifically the MAPK/NLRP3 and JAK1/STAT6 pathways. These results indicate that CSE is a promising candidate for the management of AD. Despite the recognized limitations, such as the need for comparative studies with isolated compounds, our findings suggest that CSE possesses substantial potential as a valuable nutraceutical and cosmeceutical resource. Ultimately, CSE represents a high-value material with significant prospects for both therapeutic and industrial applications.”

https://www.mdpi.com/2072-6643/18/14/2382

Phytochemistry, bioactivity, and medicinal use of Cannabis sativa roots: a comprehensive review

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“Background: Cannabis sativa is among the earliest domesticated plants and has been widely utilized for nutritional, industrial, and medicinal purposes. While its aerial parts, particularly the leaves and inflorescences, have been extensively studied due to their recreational and therapeutic applications, the roots remain comparatively neglected, despite their long-standing use in traditional medicine for treating wounds, burns, and inflammation.

Aim: This review aims to summarize the current knowledge on the phytochemical composition and biological activities of C. sativa roots, with emphasis on their pharmacological potential. RESULTS: The roots of C. sativa contain a diverse spectrum of secondary metabolites, including phytosterols, alkaloids, terpenes, and phenolic compounds. These bioactive constituents have been reported to exert antioxidant, anti-inflammatory, and antimicrobial activities. In vivo studies further demonstrate nociceptive and antispasmodic effects, with no evidence of cytotoxicity.

Conclusion: C. sativa roots represent an underexplored pharmacognostic resource with significant potential for the discovery of novel bioactive compounds. Their chemical diversity and biological activities provide a strong rationale for renewed scientific attention, supporting future research into this underestimated part of a species of growing medical and economic relevance.”

https://pubmed.ncbi.nlm.nih.gov/42477783

https://link.springer.com/article/10.1186/s42238-026-00470-4

Effects of cannabidiol in comparison to hormonal therapy on estrogen decline-induced memory impairments and endocannabinoid system in rats

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“The aim of this study was to investigate the effects of cannabidiol (CBD) on memory deficits induced by ovariectomy and to directly compare its effects with those of hormone therapy, in order to better understand potential shared mechanisms related to menopause-associated cognitive decline, with a particular focus on the endocannabinoid system.

Three-month-old female Wistar rats were randomly assigned to four experimental groups: SHAM-Veh (Vehicle), OVX-Veh, OVX-E2 (estradiol), and OVX-CBD. Animals underwent either bilateral ovariectomy or sham surgery. Following a three-week recovery period, rats received daily subcutaneous injections of CBD (10 mg/kg), estradiol (10 μg/kg), or vehicle for 21 consecutive days. Behavioral assessments included object recognition and fear-motivated memory tests. Twenty-four hours after the final treatment, animals were euthanized for neurochemical and molecular analyses. Levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured using high-performance liquid chromatography. Gene expression of cannabinoid receptors CB1 and CB2, as well as enzymes involved in the synthesis and degradation of endocannabinoids (NAPE-PLD, DAGL-A, FAAH, and MGLL), was evaluated in the hippocampus by RT-qPCR.

The results demonstrated that CBD treatment produced memory improvements in the object recognition task comparable to those observed with estradiol. Ovariectomy-induced impairments in fear-motivated memory were completely reversed by both CBD and estradiol treatments. Additionally, CBD reduced the expression of FAAH and MGLL, resulting in increased hippocampal levels of AEA and 2-AG, effects similar to those observed with hormone therapy. Estradiol also increased NAPE-PLD expression, contributing to elevated AEA levels.

Overall, the findings suggest that CBD exerts a protective effect on memory comparable to standard estrogen therapy, supporting its therapeutic potential for menopause-related cognitive impairments.”

https://pubmed.ncbi.nlm.nih.gov/42476954

https://onlinelibrary.wiley.com/doi/10.1111/jne.70234


Endocannabinoid system modulation in bruxism: a neurobiological hypothesis and translational model of ECS-targeted intervention

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“Bruxism is a multifactorial motor behavior of predominantly central origin, characterized by repetitive masticatory muscle activity and associated with dysregulation of dopaminergic, serotonergic, GABAergic, and glutamatergic pathways involved in motor control, emotional regulation, and stress responsivity.

The endocannabinoid system (ECS) has emerged as a key homeostatic neuromodulator capable of integrating these neurotransmitter systems, thereby influencing pain processing, sleep-wake dynamics, and motor output.

This article develops a neurobiological hypothesis based on a narrative integrative synthesis of clinical, experimental, and translational evidence regarding ECS involvement in the pathophysiology of bruxism.

Findings from randomized clinical trials suggest that topical cannabidiol (CBD) may modulate motor neuron excitability and reduce pain-related outcomes, while case-based and experimental evidence supports the interaction between cannabinoid signaling and neural circuits implicated in motor control and behavioral regulation.

Building on this evidence, we propose a hypothesis-driven translational model in which ECS-mediated neuromodulation may influence central mechanisms underlying bruxism, including motor pattern generation, stress responsivity, and nociceptive processing.

Rather than providing prescriptive therapeutic recommendations, this model is intended as a hypothesis-generating construct that integrates current knowledge on ECS signaling within the broader neurobiology of motor control. Although heterogeneity in study design and outcome measures limits definitive conclusions, the available evidence supports the ECS as a plausible modulatory system in bruxism, with potential implications for future mechanistic and clinical research in centrally mediated motor disorders.”

https://pubmed.ncbi.nlm.nih.gov/42459362

“In summary, the integration of neurobiological knowledge about bruxism with advances in understanding the endocannabinoid system supports the development of a hypothesis-driven translational model in which ECS-mediated neuromodulation may represent a relevant pathway for influencing centrally mediated motor behaviors.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1854001/full


Hemp: A Sustainable Plant with High Industrial Value in Food Processing

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“In the era of SDGs, useful plants which provide valuable industrial outputs and at the same time pose less impact on the environment should be explored.

Hemp seems one of the most relevant gluten-free crop plants to meet such requirements. Its high nutritional value is comparable to soy. Moreover, almost the whole body of the hemp plant has a wide array of utility: industrial production of food, fiber, and construction materials. In view of environmental sustainability, hemp requires less pesticides or water in cultivation compared to cotton, a representative fiber plant.

This short review investigates hemp’s sustainability as a plant as well as its utility value as a highly nutritional material in the food industry. Recent application research of hemp protein in food processing includes plant milk, emulsifiers, fortification of gluten-free bread, plant-based meat production, as well as membrane formation.

These studies have revealed distinctive properties of hemp protein, especially in relation to disulfide (S-S)/sulfhydryl (-SH)-mediated interactions with protein from other sources. While its cultivation area and industrial use were limited for a while over confusion with marijuana, the market for industrial hemp is growing rapidly because it has been highly reevaluated in multiple areas of industry.

Conclusively, with its sustainability as a plant as well as its distinctive useful property of the seed protein, hemp has promising value in the development of new foods.”

https://pubmed.ncbi.nlm.nih.gov/36766179

“Hemp is a sustainable plant requiring less water or pesticides in cultivation compared to cotton. It has a short growth period and almost its whole plant body has versatile utility value. Hemp seeds are high-protein, low-carbohydrate, and rich in dietary fiber and unsaturated fatty acids. After expression of oil from the seeds, the residual mass is a useful protein-rich material for food processing. Moreover, hemp seed protein has distinctive characteristics suitable for developing new foods such as an emulsifier, plant-based meat, and gas-retaining membrane. The cysteine-rich protein feature realizes unique disulfide-mediated interactions with protein from other sources and is thus expected to facilitate development of new food materials. Meanwhile, hemp protein is reported to be less soluble, and a higher temperature is needed for processing compared to other plant protein. Therefore, suitable reaction conditions should be investigated for future application in the food industry. Further scientific understanding will facilitate expanded use of this less-investigated protein compared to soy protein. Conclusively, hemp is a suitable plant with versatile utility in this SDGs era. Hemp seeds and the protein are expected to be promising food materials in the food industry.”

https://www.mdpi.com/2304-8158/12/3/651


Edible Oil-Based Extraction of Cannabis sativa L. Roots: Effect of Solvent and Temperature on Friedelin Yield and Antioxidant Activity

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“The roots of Cannabis sativa L., historically overlooked, are gaining attention as a potential source of bioactive compounds with antioxidant, antimicrobial, and anti-inflammatory properties.

While previous studies have focused on extractions using ethanol, water, or supercritical CO2, the feasibility of edible oil-based extraction remains largely unexplored.

This study evaluated the extraction of root compounds using hemp seed oil, MCT coconut oil, and grape seed oil at six temperatures (50-90 °C).

Extracts were analyzed by GC-MS for compound identification and quantification, and antioxidant activity was assessed using the DPPH assay, ABTS test and β-carotene bleaching method, with results statistically evaluated by ANOVA. Friedelin was successfully extracted with all oils, with grape seed oil yielding the highest concentration (0.810 mg/g dry roots), achieving recoveries higher than those previously reported for ethanol-based extractions.

All extracts demonstrated positive antioxidant activity, with grape seed oil, both alone and combined with extracts, showing higher values across the three methods. ANOVA revealed a significant effect of solvent type on both Friedelin concentration and antioxidant capacity.

These results demonstrate that edible oils are effective solvents for extracting bioactive compounds from C. sativa roots, supporting their potential application in cosmetic or medicinal formulations.”

https://pubmed.ncbi.nlm.nih.gov/42123839

“In conclusion, this research validates the feasibility of extracting bioactive compounds from cannabis roots using accessible edible oils, achieving Friedelin recoveries higher than those previously reported for alcoholic extractions. These findings provide an important foundation for the development of Cannabis sativa L. root-based products for cosmetic or medicinal applications.”

https://www.mdpi.com/1420-3049/31/9/1473


Cannabis sativa: A Source of Antiparasitic Compounds?

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“Cannabis sativa (hemp, marijuana, ganja) is a plant with industrial, medicinal, and recreational uses that synthesizes phytocannabinoids, a group of compounds from which tetrahydrocannabinol (THC) and cannabidiol (CBD) outstand by their known high and low psychoactive properties.

These and other cannabinoids (endocannabinoids and synthetic derivatives with modulating effects over cannabinoid receptors CB1/2) have been tested in vitro using cultured parasites and in vivo in rodent models of protozoosis affecting the central nervous system as are amoebic encephalopathy, cerebral malaria, brain toxoplasmosis as well as Chagas disease and Leishmaniasis. Helminthiasis mainly includes Nippotrongyloidosis and Schistosomiasis and even their effects on ticks as Boophilus have been reported.

The parasiticidal effect of C. sativa extracts and cannabinoids is consistently found although some points of concern arise from animal models because CB1 or CB2 inactivation/inhibition led to distinct outcomes –beneficial or deleteriousin parasite load and host survival, depending on the organism studied. Possible parasitic targets of cannabinoids include arginase, acetylcholinestherase and haemozoin, a product of hemoglobin digestion.

Collectively, these data highlight that the potential use of cannabinoids against parasitic infections should consider the effects of these compounds on their known targets at the endocannabinoid system (CB1/2) and the likely target(s) in parasites.”

“Plant-derived compounds have multiple beneficial activities for human health, including new candidates for the treatment of parasitic diseases. Among these are macrocyclic lactones terpenes and polyphenols. Unlike most plant species, C. sativa (hemp, marijuana or ganja) is a rich source of both products of industrial interest and phytomedicinal compounds as well”

“At the light of experimental evidence, the potential application of cannabinoids in parasitosis is generally promising on the basis of their parasiticidal in vitro activities”

https://biomedres.us/fulltexts/BJSTR.MS.ID.007960.php