Cannabinoids and the endocannabinoid system in liver diseases

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“Cannabinoids are biologically active substances acting via feedback-coupled CB1 and CB2 receptors. Their expression in myofibroblasts and liver endothelial cells is reported to be elevated in chronic liver diseases. The effect of CB1 receptor stimulation is to increase fibrosis and inflammatory activity in the liver by stimulating stellate cells, while activation of the CB2 receptor results in inhibition of fibrosis. Stimulation of the CB1 receptor may also lead to progression of liver steatosis and carcinogenesis. In end-stage liver disease, the endocannabinoid system plays an important role in the pathogenesis of encephalopathy and vascular effects, such as portal hypertension, splanchnic vasodilatation and cirrhotic cardiomyopathy. It seems that interference in endocannabinoid transmission may serve as an attractive target for the development of hepatological drugs.”

https://pubmed.ncbi.nlm.nih.gov/40290527/

https://www.termedia.pl/Cannabinoids-and-the-endocannabinoid-system-in-liver-diseases,80,55209,0,1.html

The Endocannabinoid System in Cancer Biology: A Mini-Review of Mechanisms and Therapeutic Potential

“The Endocannabinoid System (ECS) plays a critical role in maintaining physiological homeostasis, influencing a range of processes such as neuroprotection, inflammation, energy metabolism, and immune responses.

Comprising cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and degradation, the ECS has attracted increasing attention in cancer research. Cannabinoid receptor activation has been associated with the regulation of cancer-related processes, including cell proliferation, apoptosis, and angiogenesis, suggesting that the ECS may have a role in tumor progression and cancer treatment.

Preclinical studies have shown that cannabinoids, through their interaction with CB1 and CB2 receptors, can inhibit tumor cell growth, induce programmed cell death, and suppress the formation of new blood vessels in various cancer models.

Despite these encouraging findings, the clinical translation of ECS-targeted therapies remains in its early stages. The complexity of tumor heterogeneity, the variability in patient responses, and the challenges associated with the pharmacokinetics of cannabinoids are significant obstacles to the broader application of these findings in clinical settings.

This review provides an overview of the current understanding of the ECS’s involvement in cancer biology, focusing on key mechanisms by which it may influence carcinogenesis. Additionally, we discuss the therapeutic potential of targeting the ECS in cancer treatment, while highlighting the limitations and uncertainties that need to be addressed through ongoing research.”

https://www.frontiersin.org/journals/oncology-reviews/articles/10.3389/or.2025.1573797/abstract

New Cannabinoids and Chlorin-Type Metabolites from the Flowers of Cannabis sativa L.: A Study on Their Neuroblastoma Activity

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“Background/ObjectivesCannabis sativa has been utilized for medical purposes for thousands of years. It continues to be recognized as a plant with an extensive variety of medicinal and nutraceutical uses today. In this study, a chemical investigation of the flowers of C. sativa isolated by using a variety of chromatographic techniques led to the isolation of eleven compounds. These purified compounds were evaluated for antitumor activity against SK-N-SH neuroblastoma cells. 

Methods: The compounds were isolated by using chromatographic techniques. Their structures were identified by the examination of spectroscopic methods, including 1D (1H, 13C, and DEPT) and 2D (COSY, HSQC, HMBC, and NOESY) nuclear magnetic resonance (NMR) spectra and mass spectrum, together with the comparison to those reported previously in the literature. The evaluation of toxicity on SK-N-SH cells was performed by the MTT method. 

Results: Eleven compounds were isolated from the flowers of C. sativa, including two new compounds, namely cannabielsoxa (1), 132-hydroxypheophorbide c ethyl ester (2), and six known cannabinoids (611), together with the first isolation of chlorin-type compounds: pyropheophorbide A (3), 132-hydroxypheophorbide b ethyl ester (4), and ligulariaphytin A (5) from this plant. The results also demonstrated that cannabinoid compounds had stronger inhibitory effects on neuroblastoma cells than chlorin-type compounds. 

Conclusions: The evaluation of the biological activities of compounds showed that compounds 410 could be considered as the potential compounds for antitumor effects against neuroblastomas. This is also highlighted by using docking analysis. Additionally, the results of this study also suggest that these compounds have the potential to be developed into antineuroblastoma products.”

https://pubmed.ncbi.nlm.nih.gov/40283956/

“This reinforces confidence that a cannabis extract enriched in cannabinoids has the potential to be a promising candidate for neuroblastoma treatment.”

https://www.mdpi.com/1424-8247/18/4/521

Cannabidiol as a novel therapeutic agent in breast cancer: evidence from literature

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“Background: Breast cancer is one of the most prevalent cancers worldwide, posing significant challenges due to its heterogeneity and the emergence of drug resistance. Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has recently gained attention for its potential therapeutic effects in breast cancer.

Objective: This review aims to evaluate the antitumor effects of CBD in breast cancer treatment by synthesizing preclinical and clinical evidence, elucidating its mechanisms of action, and exploring its translational potential.

Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive search was performed across PubMed, Google Scholar, Web of Science, and Scopus databases, using keywords such as “Cannabidiol,” “CBD,” “Breast Cancer,” “Therapeutic Agent,” and “Antitumor Effects.” A total of 1,191 articles were initially identified. After duplicate removal and eligibility screening, 34 studies published between 1998 and 2025 were selected, including in vitro, in vivo, and clinical investigations. Studies were assessed based on PRISMA recommendations, considering inclusion criteria such as CBD’s impact on apoptosis, cell proliferation, tumor progression, and molecular mechanisms.

Results: CBD demonstrated significant anticancer effects, including induction of apoptosis, inhibition of cell proliferation, suppression of metastasis, and modulation of the tumor microenvironment. Mechanistically, CBD modulates key pathways such as PI3K/Akt, mTOR, and PPARγ and interacts with CB1, CB2, and non-cannabinoid receptors. Preclinical studies showed CBD’s efficacy, particularly in triple-negative breast cancer (TNBC), while limited clinical trials highlighted its potential as an adjunct to conventional therapies.

Conclusion: CBD offers a promising therapeutic approach for breast cancer, especially for aggressive subtypes like TNBC. However, challenges such as variability in study design, lack of standardized protocols, and limited clinical validation hinder its clinical application. Future research should focus on conducting robust clinical trials, identifying predictive biomarkers, and optimizing combinatorial therapies to integrate CBD into personalized cancer treatment strategies.”

https://pubmed.ncbi.nlm.nih.gov/40275168/

“CBD holds significant promise as a complementary or standalone therapeutic agent in breast cancer treatment, particularly in TNBC, where conventional options are limited. However, clinical validation through well-designed trials, biomarker identification, and safety profiling remains imperative before widespread clinical adoption. Future studies should focus on optimizing combinatorial therapies, investigating long-term effects, and refining pharmacological formulations to bridge the gap between preclinical findings and clinical application. By addressing these challenges, CBD could potentially redefine breast cancer management strategies, offering a safer, more effective, and targeted approach to treatment.”

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14175-z

The endocannabinoid and paracannabinoid systems in natural reward processes: possible pharmacological targets?

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“Natural rewards such as food, mating, and social interaction are essential for survival and species preservation, and their regulation involves a complex interplay of motivational, cognitive, and emotional processes.

Over the past two decades, increasing attention has been directed toward the endocannabinoid system and its paracannabinoid counterpart as key modulators of these behaviors.

This review aims to provide an integrated overview of the roles played by the endocannabinoid and paracannabinoid systems in regulating natural reward-driven behaviors, focusing on feeding, reproductive behavior, and social interaction.

We highlight how the endocannabinoid system – mainly through CB1 receptor signaling – modulates central and peripheral circuits involved in energy homeostasis, reward processing, and emotional regulation. In parallel, we explore the role of paracannabinoids, such as oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA), which act primarily via non-cannabinoid receptors and contribute to the regulation of appetite, sexual motivation, and social behavior.

Special attention is given to the relevance of these systems in the pathophysiology of obesity, eating disorders, sexual dysfunctions, and social impairments, as well as their potential as pharmacological targets.

Overall, the evidence discussed supports a broader conceptualization of endocannabinoid and paracannabinoid signaling as pivotal regulators of natural rewards and opens new avenues for the development of targeted interventions for motivational and reward-related disorders.”

https://pubmed.ncbi.nlm.nih.gov/40274041/

“Endocannabinoid/paracannabinoid therapies offer promising innovative drug development.”

https://www.sciencedirect.com/science/article/pii/S0031938425001301?via%3Dihub

Impaired mnemonic pattern separation associated with PTSD symptoms paradoxically improves with regular cannabis use

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“Posttraumatic stress disorder (PTSD) is associated with poor hippocampal function and disrupted pattern recognition. Cannabis use is highly prevalent in individuals with PTSD, yet the impact on these cognitive functions is poorly understood. Participants (n = 111) with a range of PTSD symptoms with and without regular cannabis use completed the mnemonic similarity task. We hypothesized that regular use would be associated with alterations in pattern separation ability in individuals with PTSD symptoms. High PTSD symptoms were associated with reduced pattern separation performance in minimal users. Regular users with high PTSD symptoms showed greater pattern separation, but reduced pattern separation with low PTSD symptoms. These results suggest that regular cannabis use may disrupt pattern separation and similar hippocampal-dependent processes, while it may improve pattern separation in individuals with high PTSD symptoms. These cross-sectional results require longitudinal follow-up studies to evaluate the causal effects of regular cannabis use on cognitive function in PTSD.”

https://pubmed.ncbi.nlm.nih.gov/40274935/

“The finding that regular cannabis use was associated with improved pattern separation ability in those reporting more severe PTSD symptoms was unexpected. One possible explanation for this observation is that the endocannabinoid system is altered by trauma exposure and in PTSD.”

https://www.nature.com/articles/s44184-025-00126-w

Emerging nano-derived therapy for the treatment of dementia: a comprehensive review

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“Dementia includes a variety of neurodegenerative diseases that affect and target the brain’s fundamental cognitive functions. It is undoubtedly one of the diseases that affects people globally. The ameliorating the disease is still not known; the symptoms, however, can be prevented to an extent. Dementia encompasses Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Lewy body dementia, mixed dementia, and various other diseases.

The aggregation of β-amyloid protein plaques and the formation of neurofibrillary tangles have been concluded as the foremost cause for the onset of the disease. As the cases climb, new neuroprotective methods are being developed in the form of new drug delivery systems that provide targeted delivery.

Herbal drugs like Ashwagandha, Brahmi, and Cannabis have shown satisfactory results by not only treating the symptoms but have also been shown to reduce and ameliorate the formation of amyloid plaque formation.

This article explores the intricate possibilities of drug delivery and the absolute use of herbal drugs to target neurodegenerative diseases. The various possibilities of nanotechnology currently available with new emerging techniques are also discussed.”

https://pubmed.ncbi.nlm.nih.gov/40268841/

https://link.springer.com/article/10.1007/s13346-025-01863-3

Cannabidiol and cognitive functions/inflammatory markers in Parkinson’s disease: A double-blind randomized controlled trial at Buriram Hospital (CBD-PD-BRH trial)

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“Introduction: Cannabidiol (CBD) may alleviate Parkinson’s disease (PD) symptoms, but its cognitive and anti-inflammatory effects remain unclear due to limited randomized trials. This study evaluates CBD’s efficacy in PD patients.

Methods: Sixty PD patients were randomized into CBD (n = 30) or placebo (n = 30) groups. The CBD group received a sublingual CBD-enriched product (101.9 mg/ml CBD, 4.8 mg/ml tetrahydrocannabinol [THC]). The primary outcome was improvement in the Montreal Cognitive Assessment (MoCA) delayed recall scores. Secondary outcome measures included other MoCA components, the total MoCA score, motor examination, anxiety/depression, inflammatory markers, renal/liver function, and adverse events. CBD and THC levels were measured at 12 weeks.

Results: Nine patients were lost to follow-up, leaving 51 participants (CBD: 27; placebo: 24) for analysis. The mean CBD dose was 26 mg/day, and THC was 1.2 mg/day. CBD was detected in 17 patients (mean: 2 ng/ml), with no THC found. Delayed recall scores showed no group differences. The CBD group improved naming scores (mean difference: 0.37, 95 % CI: 0.01 to 0.73). Language scores increased in the placebo group but remained unchanged in the CBD group. Inflammatory markers and other outcomes showed no differences, except for elevated alkaline phosphatase in the CBD group, with no serious side effects in either group.

Conclusions: In this 12-week trial, 26 mg/day of sublingual CBD was safe, with no adverse effects on motor, cognitive, or affective symptoms in PD patients, and improved MoCA naming scores. Future studies should investigate higher doses and use targeted naming tests.”

https://pubmed.ncbi.nlm.nih.gov/40267585/

https://www.prd-journal.com/article/S1353-8020(25)00582-6/abstract

The role of tetrahydrocannabivarin (THCV) in metabolic disorders: A promising cannabinoid for diabetes and weight management

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“Disorders of the metabolism, including obesity and type 2 diabetes, represent significant global health challenges due to their rising prevalence and associated complications. Despite existing therapeutic strategies, including lifestyle interventions, pharmacological treatments, and surgical options, limitations such as poor adherence, side effects, and accessibility issues call attention to the need for novel solutions.

Tetrahydrocannabivarin (THCV), a non-psychoactive cannabinoid derived from Cannabis sativa, has emerged as a promising agent to manage metabolic disorders.

Unlike tetrahydrocannabinol (THC), THCV exhibits an antagonistic function on the CB1 receptor and a partial agonist function on the CB2 receptor, thus enabling appetite suppression, enhanced glucose regulation, and increased energy expenditure.

Preclinical studies demonstrated that THCV improves insulin sensitivity, promotes glucose uptake, and restores insulin signaling in metabolic tissues. Additionally, THCV reduces lipid accumulation and improves the mitochondrial activity in adipocytes and hepatocytes, shown through both cell-based and animal research. Animal models further revealed THCV’s potential to suppress appetite, prevent hepatosteatosis, and improve metabolic homeostasis.

Preliminary human trials support these findings, thereby showing that THCV may modulate appetite and glycemic control, though larger-scale studies are necessary to confirm its clinical efficacy and safety. THCV’s unique pharmacological profile positions it as a possible therapeutic candidate to address the multifaceted challenges of obesity and diabetes. Continued research should concentrate on optimizing formulations, undertaking well-designed clinical studies, and addressing regulatory hurdles to unlock its full potential”

https://pubmed.ncbi.nlm.nih.gov/40270953/

https://www.aimspress.com/article/doi/10.3934/Neuroscience.2025003

Cannabinoids in neuropathic pain treatment: pharmacological insights and clinical outcomes from recent trials

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“Neuropathic pain, a complex and often devastating condition, poses significant challenges for its effective management. Despite promising research on various cannabis formulations and delivery methods for neuropathic pain, significant gaps remain in our knowledge.

While inhaled cannabis shows analgesic effects and alternative delivery methods may improve bioavailability, oral formulations have yielded mixed results, often limited by small sample sizes and placebo effects. Therefore, further research is essential to optimize cannabis formulations, identify responder profiles to tailor treatments effectively, and, most critically, confirm the long-term safety and efficacy of cannabis-based therapies in managing NP.

This review article aims to provide a comprehensive analysis of the therapeutic potential of cannabis-based medicines, with a particular focus on cannabinoids. This review, though not systematic, examines 11 clinical studies, specifically Randomised Clinical Trials) published from 2014 to 2024, highlighting the efficacy of numerous cannabis formulations, in alleviating neuropathic pain.

Key findings show that cannabinoids can reduce pain perception, improve patient quality of life, and mitigate other symptoms associated with neuropathic pain.

The synergistic effects of tetrahydrocannabinol and cannabidiol are discussed, emphasizing their ability to enhance analgesic effects, while potentially reducing the psychoactive side effects of tetrahydrocannabinol.

This review emphasizes the importance of the personalized approach to improve therapeutic outcomes. Limitations of the existing research focusing on cannabis for neuropathic pain are limited by heterogeneity, lack of standardization, small sample sizes, and reliance on subjective outcomes, impacting the reliability and generalizability of findings. However, this exhaustive review aims to inform clinicians and researchers about the evolving role of cannabis in contemporary pain management strategies, illustrating the diverse pharmacological profiles of cannabinoids and their potential as adjunct therapies for neuropathic pain management.”

https://pubmed.ncbi.nlm.nih.gov/40261351/

https://link.springer.com/article/10.1007/s00210-025-04134-7