Category Archives: Uncategorized

Immunomodulatory effect of Cannabis root extract on inflammatory cascades via endocannabinoid system regulation

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“Cannabis roots have been widely used in traditional medicine, with documented references in classical texts describing their use for the treatment of various inflammatory diseases and pain. Despite their longstanding ethnopharmacological significance, the bioactive compounds responsible for these effects and their underlying mechanisms remain unexplored. The present study was conducted to evaluate the unique anti-inflammatory mechanisms of Cannabis sativa root fractions, and moreover, to investigate its mechanism related with the endocannabinoid system (ECS).

Methods

Antioxidant activities and phenol contents of various Cannabis root fractions were determined by chemical assays. The effects of cannabis root fractions on inflammatory markers and endocannabinoid receptor (CB1, CB2) levels were evaluated in LPS-stimulated RAW 264.7 cells. Intracellular 2-arachidonoylglycerol (2-AG) levels were measured using LC-MS/MS. The fraction with the highest potential was further investigated to elucidate its mechanism using endocannabinoid receptor antagonists.

Results

Among the fractions, ethyl acetate fraction (CSREA) demonstrated the highest potential in both antioxidant and anti-inflammatory effects. However, its effect was not attributed to the inhibition of NF-κB signaling pathways. LC-MS/MS analysis showed that CSREA affected intracellular 2-AG levels, supporting its potential via the ECS. CSREA also effectively suppressed ERK phosphorylation, a critical inflammatory signaling pathway modulated by ECS. However, CSREA activity was reduced by co-treatment with a CB1 antagonist.

Conclusion

This study demonstrates that CSREA suppresses inflammatory responses and restores cellular homeostasis primarily by regulating the endocannabinoid system. However, its exclusive use of an acute in vitro inflammation model represents a limitation, and the effects of CSREA in chronic and in vivo settings require further investigation.”

https://link.springer.com/article/10.1186/s12906-026-05317-2

Cannabidiol-rich extract suppresses the activation of proinflammatory genes IL-1β and IL-6 in equine mesenchymal stem cells stimulated with lipopolysaccharide

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“Peripheral nerve injuries (PNI) often lead to long-term functional impairment. Mesenchymal stem cells (MSCs) and cannabidiol (CBD) have shown anti-inflammatory and neuroprotective effects in vitro, which may be relevant for PNI research.

The aim of this study was to evaluate CBD-rich cannabis extract’s potential to induce anti-inflammatory and neurotrophic gene expression in equine adipose tissue-derived MSCs (EqAT-MSCs) in an inflammatory in vitro environment.

The morphology and metabolic activity of EqAT-MSCs (n = 4) were assessed after CBD-rich extract priming at concentrations of 3, 5, 7, and 9 µM for 24 and 48 h. Cytokine and neurotrophic gene expression was evaluated under these conditions: DMEM (unprimed), DMEM + LPS (lipopolysaccharide) (10 ng/ml), and LPS (10 ng/ml) + DMEM + CBD at 3, 5, and 7 µM for 24 and 48 h. No morphological changes were observed in primed EqAT-MSCs versus unprimed cells. EqAT-MSCs showed a reduction in metabolic activity at 9 µM after 24 h. CBD priming following LPS stimulation led to statistically significant changes in EqAT-MSC gene expression. BDNF expression increased after 48 h (3 and 5 µM), while NGF expression decreased at both 24 and 48 h (3, 5, and 7 µM). IL-1β expression decreased after 24 h (3 and 7 µM), and IL-6 levels decreased at both 24 (5 and 7 µM) and 48 h (3, 5, and 7 µM). No significant changes were observed in GDNF, TNF-ɑ, IFN-ɣ, or IL-10.

These results indicate that CBD-rich extract selectively modulates inflammatory and neurotrophic gene expression in EqAT-MSCs while maintaining metabolic integrity.”

https://link.springer.com/article/10.1007/s11259-026-11105-7

Cannabidiol mitigates secondary genital injury after thoracic trauma by regulating systemic inflammation and hormone receptor signaling

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“Blunt thoracic trauma-induced pulmonary contusion is a major cause of acute lung injury and triggers a systemic inflammatory response characterized by cytokine release, oxidative stress, and apoptosis. These systemic effects may disrupt vascular homeostasis and contribute to secondary injury in distant organs, particularly within the female reproductive system, which is dependent on vascular and hormonal balance.

This study evaluated the effects of cannabidiol (CBD), a non-psychotropic phytocannabinoid with anti-inflammatory, antioxidant, and anti-apoptotic properties, on secondary reproductive organ injury following blunt thoracic trauma.

Forty adult female Wistar albino rats were assigned to Sham, Trauma, Trauma + CBD, and CBD groups. Pulmonary contusion was induced using a standardized weight-drop model (200 g from 1 m), and CBD (5 mg/kg, i.p.) was administered 30 min before trauma. Forty-eight hours later, lung, ovary, uterus, and fallopian tube tissues were collected for histopathological and immunohistochemical analyses. Trauma induced pulmonary injury accompanied by degenerative changes in reproductive tissues, including reduced estrogen receptor (ER) expression and increased hypoxia-inducible factor-1α (HIF-1α) and oxytocin receptor (OTR) expressions.

CBD treatment attenuated pulmonary and reproductive tissue injury, preserved ER immunoreactivity, and reduced HIF-1α and OTR expression.

These findings indicate that CBD mitigates secondary reproductive organ injury after thoracic trauma by modulating systemic inflammatory responses and regulating receptor expression, suggesting its potential role as a cytoprotective agent in trauma-related multi-organ injury.”

https://pubmed.ncbi.nlm.nih.gov/41723193

https://www.nature.com/articles/s41598-026-39310-z

The Paradoxical Effect of Cannabis Use on Cognition in Chronic Psychotic Disorders

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“Background/objectives: Cannabis use has a particularly high prevalence in individuals with psychotic disorders. Although cannabis use is generally associated with cognitive impairments in the general population, its impact on cognition in psychosis remains controversial. This study aimed to investigate the association between cannabis use and cognitive performance in a cohort of individuals affected by psychotic disorders.

Methods: A total of 105 inpatients with psychotic disorders (mean age: 40.3 years; 34 females) were recruited from the University Hospital Center “Mother Teresa” in Tirana. Data collection included socio-demographic and clinical variables. Cognitive functioning was evaluated using the Montreal Cognitive Assessment (MoCA), while psychopathology was assessed with the Brief Negative Symptom Scale (BNSS), the Calgary Depression Scale for Schizophrenia (CDSS), the Psychotic Symptom Rating Scales (PSYRATS), and the Scale for the Assessment of Thought, Language, and Communication (TLC).

Results: Cannabis users (CU) were more frequently male, younger, and exhibited an earlier onset of psychosis compared to non-users (No-CU). Importantly, CU demonstrated higher MoCA scores, with the most favorable outcomes observed among daily users.

Conclusions: Contrary to the prevailing assumption that cannabis use exacerbates cognitive decline, our findings indicate an unexpected association between cannabis use and preserved cognitive functioning in psychosis. These results underscore the need to consider dosage, frequency, and cannabinoid composition (THC/CBD ratio) when interpreting cannabis-related cognitive outcomes in psychotic disorders.”

https://pubmed.ncbi.nlm.nih.gov/41718389

“the present study highlights that, in certain cases, patients with psychosis who use cannabis may demonstrate relatively preserved or even superior cognitive performance compared with non-using patients. These results raise important clinical and research questions.”

https://www.mdpi.com/1873-149X/33/1/11

Activation of Cannabinoid Receptor 1 Enhances Wound Healing by Promoting the Proliferative Phase

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“The mechanisms underlying wound healing mediated by cannabinoid receptor 1 (CB1)-known for its neuromodulatory functions-remain incompletely understood. Therefore, we investigated the impact of activating CB1 using specific agonists, both in vitro and in vivo, with a focus on wound healing.

In the in vitro study, fibroblasts were isolated and cultured from the dermis of human skin and treated with a CB1 agonist, 2-arachidonyl glyceryl ether (2-AGE). In the in vivo study, a mouse acute wound model was created using a skin biopsy punch and treated with the CB1 agonist arachidonoyl 2′-chloroethylamide (ACEA).

The in vitro study revealed that 2-AGE increased cell proliferation and differentiation, upregulated the expression of alpha-smooth muscle actin (α-SMA), N-cadherin, and vimentin, and enhanced cell migration as well as the synthesis of type I and III collagen and fibronectin in normal human dermal fibroblasts. The CB1 antagonist AM251 abolished 2-AGE-induced expression of α-SMA, type I collagen, and fibronectin. In vivo, ACEA treatment accelerated wound closure, increased expression of α-SMA, type I collagen, and fibronectin, and ultimately increased epidermal and dermal thickness.

Overall, these findings suggest that the activation of CB1 promotes wound healing and provides evidence for the therapeutic potential of CB1 agonists in wound treatment.”

https://pubmed.ncbi.nlm.nih.gov/41683598

“Recent research has highlighted the role of the endocannabinoid system (ECS) in skin physiology and repair.”

“Clinical evidence indicates that the topical application of Cannabis-Based Medicines (TCBMs) facilitates tissue repair and promotes complete wound closure in previously refractory wounds.”

“In conclusion, our findings support the hypothesis that CB1 receptor activation facilitates wound healing through both cellular and molecular mechanisms.”

“Thus, these findings strongly support the therapeutic potential of targeting specific agonists as a viable strategy to accelerate the proliferative or contractile phases and thereby enhance the rate of wound healing.”

https://www.mdpi.com/1422-0067/27/3/1171


Role of Endocannabinoid System Perturbation in Organophosphate-Mediated Metabolic Impairment and Neuroinflammation

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“Organophosphates have been used for decades as pesticides, insecticides and herbicides, both in agricultural and industrial settings. However, their toxic effects on multiple body systems limit their safety. The clinical presentation of organophosphate toxicity varies depending on the route and duration of exposure. Although most research is focused on their cholinergic toxicity, emerging evidence points to their crucial contribution to metabolic dysfunction, including Type 2 diabetes and neuroinflammation.

Beyond acetylcholinesterase inhibition, recent research highlights the potential role of organophosphates in disrupting endocannabinoid signalling, particularly by affecting endogenous ligands that modulate G protein-coupled receptors. This dysregulation may contribute to organophosphate-induced metabolic disturbances and inflammation.

This review aims to explore how chronic subtoxic exposure to organophosphates contributes to metabolic syndrome and neuroinflammation through disruption of insulin and endocannabinoid signalling. It highlights the role of the endocannabinoid system in mediating these effects and evaluates its potential as a therapeutic target in organophosphate-induced toxicity.”

https://pubmed.ncbi.nlm.nih.gov/41668464

Plain language summary

“Organophosphates (OPs), commonly used as pesticides, have been shown to adversely affect both metabolism and brain health by disrupting the endocannabinoid system (ECS), a critical regulatory network involved in inflammation, energy balance, and neural function. Chronic, low‐dose exposure to OPs can alter ECS enzymes and signalling pathways, contributing to insulin resistance, obesity and neuroinflammation. These metabolic disturbances may play a key role in the development of neurodegenerative outcomes associated with OP toxicity. This review aims to examine the interplay between OPs exposure and ECS disruption, emphasizing the ECS role in pathogenesis and its potential as a therapeutic target.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.70198

Anti-inflammatory and analgesic potential of minor cannabinoids in vivo

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“The cannabis plant produces many bioactive compounds, including the major cannabinoids THC and CBD, and many lesser studied “minor” phytocannabinoids including cannabinol (CBN), cannabichromene (CBC), cannabicyclol (CBL), and cannabigerol (CBG). These compounds are touted for various ailments, including pain, inflammation, and anxiety, but experimental data on their effects are lacking, especially that of CBL, which has yet to be assessed in vivo.

Methods

To assess in vivo activity, adult male and female C57BL/6J mice were administered each compound and tested repeatedly in the tetrad battery. The potential analgesic effects in chronic pain states were assessed using the lipopolysaccharide (LPS)-induced hindpaw inflammatory pain and chronic constriction injury (CCI) neuropathic pain paradigms. Lastly, to address common psychological comorbidities of pain, CBN, CBL, and CBG were assessed in the tail suspension and marble burying tests.

Results

Cannabinol (≥ 25 mg/kg) induced classic cannabinoid effects, including acute antinociception. These effects were differentially and partially blocked by selective antagonism of CB1, adenosine A2A, or TRPV1 receptors. CBL (≥ 50 mg/kg) induced hypothermia that was fully blocked by A2A antagonism but had no apparent CB1-mediated activity. LPS-induced edema and paw proinflammatory cytokine levels were reduced by either CBN or CBL (100 mg/kg). CCI-induced cold allodynia was attenuated by either CBN (≥ 50 mg/kg) or CBL (100 mg/kg), but only at high doses that also induce catalepsy and hypothermia. None of these minor cannabinoids displayed anxiolytic- or antidepressant-like activity without concomitant locomotor effects.

Conclusions

Together, these findings suggest that CBN produces anti-inflammatory effects via cannabinoid receptor-dependent and -independent pathways, whereas CBL acts primarily through CB receptor-independent mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/41680865

https://link.springer.com/article/10.1186/s42238-025-00384-7

Health-related quality of life in patients receiving medicinal cannabis: systematic review and meta-analysis of primary research findings 2015-2025

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“Purpose: The global burden of chronic health conditions is significant. Medicinal cannabis (MC) is a legalised treatment option for patients with chronic health conditions in some countries. Health-related quality of life (HRQL) is an important patient-reported outcome across all chronic health conditions. We aimed to determine how studies of MC therapy justify, measure, and report HRQL, and assess the current evidence for HRQL following MC treatment.

Methods: Systematic review searching AMED, Medline, Web of Science, Scopus, Embase, Cinahl, and PsycINFO from Jan 2015 to Apr 2025. Studies using validated HRQL measures pre-, and post-MC treatment for any chronic health condition were included. Screening and data extraction were performed independently by two reviewers. Completeness of HRQL reporting was evaluated. Meta-analyses for short-term (2-weeks to 3-months), medium-term (> 3 to < 12-months), and long-term (≥ 12-months) HRQL outcomes were conducted, with Risk of Bias (RoB) assessed in randomised control trials (RCTs).

Results: Of 16,674 retrieved citations, 64 studies were retained for analysis:12 RCTs; 38 cohort studies; 13 case series; 1 non-randomised experimental study. Thirty-nine studies (61%) provided justification for assessing HRQL and five (8%) provided HRQL definitions. Studies used generic (n = 52, 81%) or condition-specific (n = 12, 19%) HRQL measures, with EQ-5D-5L most commonly used. Meta-analyses: RCTs showed small short-term HRQL improvements (Cohen’s d = 0.30, p = 0.03), with some concerns or low RoB. For observational studies, HRQL improved in all follow-up periods (d = 0.43 to 0.74; all p < 0.001). HRQL improvement varied between, and within, different health conditions.

Conclusion: This systematic review and meta-analyses of studies published between 2015 and 2025 found that few studies provided HRQL definitions, and a third of studies did not explain why they measured HRQL. To ensure appropriate measures are used for this important treatment outcome, future studies should define HRQL and justify the HRQL assessment in the context of research objectives.

Overall, improvements in HRQL were observed across studies of patients using MC.”

https://pubmed.ncbi.nlm.nih.gov/41621036

Plain language summary

“Medicinal cannabis (MC) is a treatment option for patients in countries where prescribing MC is legal. Health-related Quality of Life (HRQL) can mean different things to different people but remains an important treatment outcome for all patients, regardless of their specific health condition. HRQL varies depending on the context and measurement tool (questionnaire) used. We aimed to find out (1) how HRQL assessment is justified, defined and measured in MC research, and (2) if HRQL improves in patients prescribed MC. We looked at studies published over the past decade that reported HRQL in patients before and after MC treatment. Most studies (81%) used generic HRQL questionnaires (e.g., EuroQol Group: EQ-5D) and others used condition-specific questionnaires (e.g. Multiple Sclerosis Quality of Life: MSQoL-52).

Overall, HRQL improved in patients using MC.

However, only a few studies provided HRQL definitions, and a third of studies didn’t explain why they measured HRQL. This information is needed to ensure HRQL is measured and interpreted appropriately in future studies.”

https://link.springer.com/article/10.1007/s11136-026-04170-7

Cannabis sativa in the fight against drug-resistant bacteria and fungi

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“Drug resistance in bacteria and fungi is a global threat to public health. The purpose of this publication is to review the latest scientific achievements, mainly from 2020-2025, concerning the use of hemp compounds from Cannabis sativa in combating drug-resistant bacterial and fungal infections.

The literature review confirms that C.sativa, a plant with a documented centuries-old therapeutic history, is a rich source of cannabinoids and terpenes that combat drug-resistant bacteria: Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and fungi: Cryptococcus neoformans, as well as species from the Candida and Aspergillus.

The potential of hemp compounds is based on their activity in interacting directly with pathogens by disrupting cell membrane integrity, eradicating biofilm, having a bactericidal effect on bacterial spores, acting synergistically, affecting host inflammatory pathways, and the human endocannabinoid system.”

https://pubmed.ncbi.nlm.nih.gov/41607163

A CBD-rich hemp extract is superior to CBD alone in reducing relapse to methamphetamine-seeking in rats

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“In preclinical models, the non-intoxicating cannabis component cannabidiol (CBD) reduces relapse to methamphetamine (Meth)-seeking and Meth-induced hyperactivity in rats.

Cannabis products containing multiple cannabinoids (“full spectrum”) may offer greater therapeutic potential than single cannabinoid (“isolate”) products.

However, few studies tested this. This study examined whether a hemp extract (HE) containing multiple cannabinoids might be superior to CBD alone in reducing Meth-induced behavioural sensitisation and relapse, and whether serotonin 1 A receptors (5-HT1A) are involved.

Male Sprague-Dawley rats self-administered either Meth or sucrose via lever press, followed by extinction and reinstatement by Meth injection (1 mg/kg; i.p.) or sucrose access. Rats received vehicle, CBD isolate (80 mg/kg), HE (containing 2.5 mg/kg of CBD and other phytocannabinoids), or HE with CBD added to match the 80 mg/kg amount of the CBD isolate (CBD + HE condition). The 5-HT1A antagonist WAY-100635 was co-administered to assess receptor involvement. Separate rats were tested for conditioned place preference (CPP) to assess possible intrinsic rewarding properties of the cannabinoids. A final group was tested for Meth-induced behavioural sensitisation.

All CBD containing treatments reduced Meth-primed reinstatement, with HE and CBD + HE more effective than CBD isolate.

There was no effect of any treatment on reacquisition of sucrose seeking. WAY-100635 did not block the effects of any treatment. Neither cannabinoid treatment produced CPP. All treatments reduced the expression of Meth-induced sensitised hyperactivity with CBD + HE showing some superiority over CBD or HE alone.

This study suggests that CBD + HE may be more effective than CBD in reducing Meth relapse-like behaviour.”

https://pubmed.ncbi.nlm.nih.gov/41605363

“CBD-rich hemp extract surpasses CBD alone in reducing relapse to Meth-seeking.”

https://www.sciencedirect.com/science/article/pii/S0278584626000254?via%3Dihub