Category Archives: Cancer

UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols

Posted on by

“Cannabis sativa is one of the most extensively researched plant species that holds promising therapeutic and ethnomedicinal significance.

Various parts of the species including fan leaves, flowers and trichomes are well documented for their richness in cannabidiol (CBD) and tetrahydrocannabidiol (THC) contents. However, an overlooked part of C. sativa, the sugar leaves, which are wasted during harvesting has plethora of CBD and THC and yet to investigated.

In this study we investigated the ethanol extract of sugar leaves of C. sativa (CSLE) for chemical composition through UHPLC-Q-TOF-MS analysis and pharmacological potential by using various in vitro antioxidant, antidiabetic, nitric oxide inhibition and anticancer studies. Furthermore, in silicomolecular docking analysis was performed for 10 selected compounds against α-glucosidase and α-amylase.

The UHPLC-Q-TOF-MS profiling of CSLE revealed the tentative identification of 37 compounds including CBD, THC, terpenes and flavonoids. The cytotoxicity studies presented highest activity against breast cancer cell lines (MDA-MB-231, IC50= 18.12 ± 1.13 µg/mL) followed by lung, liver and colorectal cancer cell lines.

Similarly, CSLE showed significant antidiabetic activity by inhibiting α-glucosidase (IC50= 3.13 ± 2.78 µg/mL) and α-amylase. The in vitro antioxidant assays gave highest activity in ABTS followed by DPPH method as well as potentially inhibited nitric oxide (NO) formation. The computational analysis revealed good docking interaction of CBD, THC, selected terpene and flavonoids against α-glucosidase and α-amylase.

Overall, the findings present the sugar leaves of C. sativa as the undisputed rich source of CBD, THC, terpenes and flavonoids with multifaceted therapeutic potential in diabetes, inflammation and different types of cancers. However, there is need of further investigations on toxicity profile and in-depth pharmacological evaluation through in vivo disease bearing animal models.”

https://www.sciencedirect.com/science/article/abs/pii/S2950199725001429

“The research titled “UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols” identifies sugar leaves of Cannabis sativa as a potential source for multiple therapeutic compounds, including cannabidiol, terpenes, and polyphenols. Through UHPLC-Q-TOF-MS analysis, the study found that these sugar leaf extracts exhibit antioxidant, antihyperglycemic (anti-diabetic), and anticancer activities against various cancer cell lines. The specific compounds present in the sugar leaves, when combined with other plant compounds like terpenes and flavonoids, demonstrate a phenomenon known as the entourage effect, which could enhance their therapeutic potential.”

Synergistic Anticancer Effects of Fibroblast Growth Factor Receptor Inhibitor and Cannabidiol in Colorectal Cancer

Posted on by
pubmed logo

“Background/objectives: Colorectal cancer (CRC) remains a significant global health concern, with limited treatment options for metastatic stage 4 CRC. Fibroblast Growth Factor Receptor (FGFR) is a promising therapeutic target in CRC, while cannabidiol (CBD) has shown potential for inducing cell death and overcoming drug resistance. This study evaluates the efficacy of FGFR inhibitors and explores the synergistic effects of combining FGFR inhibitors with CBD in inducing apoptosis in CRC cells.

Methods: Cannabidiol and FGFR inhibitors were applied, and protein expression was analyzed via Western blot. Cell viability was assessed using the WST-1 assay, while apoptosis was measured through flow cytometry using Annexin V-FITC/PI staining. CHOP-specific siRNA transfection was performed to study gene silencing effects, followed by RNA sequencing for differential expression and pathway analysis. Statistical significance was determined using ANOVA and t-tests, with p < 0.05.

Results: FGFR expression patterns were confirmed in various cancer cell lines, with NCI-H716 showing high FGFR2 expression. Treatment with CBD (4 µM) and AZD4547 (10 nM) resulted in significant cell death, especially when used in combination, indicating the effectiveness of this combined therapy. Increased apoptosis in NCI-H716 cells was confirmed with the combined treatment. RNA sequencing and heatmap analysis suggested that ER stress might be related to the observed synergistic effect. The role of ER stress in the combination-induced apoptosis of NCI-H716 cells was further validated.

Conclusions: The combination of FGFR inhibitors and cannabidiol exhibited a synergistic effect in inducing cell death in colorectal cancer cells, likely through the ER stress pathway. This study supports the potential of combined FGFR inhibitor and CBD therapy as a promising strategy for enhancing anticancer effects in CRC.”

https://pubmed.ncbi.nlm.nih.gov/40871637/

“In conclusion, the data from this preclinical study indicate that the combination of cannabidiol (CBD) and FGFR inhibitors such as AZD4547 represents a potential therapeutic approach for metastatic colorectal cancer (CRC). This synergistic effect could help address resistance mechanisms that currently limit the efficacy of anticancer drugs. Our findings also suggest that ER stress-mediated apoptosis may be an important mechanism underlying this synergy. While these results are encouraging, further validation in appropriate preclinical animal models and, ultimately, clinical studies will be essential to confirm efficacy, assess safety, and determine the translational applicability of this combination strategy.”

https://www.mdpi.com/2072-6643/17/16/2609

The Effect of Cannabidiol in Conjunction with Radiation Therapy on Canine Glioma Cell Line Transplanted in Immunodeficient Mice

Posted on by
pubmed logo

“Glioma is a type of neoplasia that spontaneously arises from the glial cells of the brain in humans and dogs, and its prognosis is grave. Current treatment options for glioma include surgery, radiation therapy, chemotherapy, or symptomatic treatment.

Evidence has shown that cannabidiol (CBD) may have anticancer, anti-angiogenic, and anti-inflammatory properties in both in vitro and in vivo studies.

In this in vivo murine experiment, the canine glioma cell line J3TBG was injected into the frontoparietal cortex of immunodeficient mice using xenogeneic tissue transplantation. A total of 20 mice were randomly assigned to one of four treatment groups-Control group (C), CBD group (CBD), Radiation Therapy group (RT), and CBD plus Radiation Therapy group (CBD + RT). After transplantation of J3TBG, a single fraction of 5.5 Gy RT was administered to the RT and CBD + RT groups, and CBD was administered daily to the CBD and CBD + RT groups. Necropsies were performed to collect blood and brain tissue. Although there was not a statistically significant difference, the survival time among mice were longer in the CBD + RT group than the RT group.

These results indicate that CBD may be used as an adjunctive therapy to enhance RT treatment. Larger cohort studies are required to substantiate the hypothesis.”

https://pubmed.ncbi.nlm.nih.gov/40872686/

“These results indicate that CBD may be used as an adjunctive therapy to enhance the effect of radiation treatment.”

https://www.mdpi.com/2306-7381/12/8/735

Cannabidiol Is Associated with Improved Survival in Pancreatic Cancer and Modulation of Bile Acids and Gut Microbiota

Posted on by
pubmed logo

“Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies, with dismal survival rates. Cannabinoids have shown anticancer properties in various cancers, including PDAC.

This study aimed to evaluate the anticancer effects of cannabinoids, individually and in combination, and to elucidate their mechanisms of action in a murine PDAC model (KPC mice, KRASWT/G12D/TP53WT/R172H/Pdx1-Cre+/+) that mimics human disease. Additionally, the study explored the potential link between cannabinoid action, gut microbiota modulation, and bile acid (BA) metabolism.

PDAC cell lines and KPC mice were treated with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), either as monotherapy or in combination. Faecal pellets, caecal contents, plasma, and tissues were collected at the survival endpoint for analysis. BA profiling was performed using mass spectrometry, and the faecal microbiota was characterised by sequencing the V3-V4 region of the 16S rRNA gene.

While CBD and THC synergistically reduced cell viability in PDAC cell lines, only CBD monotherapy improved survival in KPC mice. Extended survival with CBD was accompanied by changes in gut microbiota composition and BA metabolism, suggesting a possible association. Notably, the effects of CBD were different from those observed with THC alone or in combination with CBD.

The study highlights a distinct role for CBD in altering BA profiles, suggesting these changes may predict responses to cannabidiol in PDAC models. Furthermore, the findings propose that targeting BA metabolism could offer a novel therapeutic strategy for PDAC.”

https://pubmed.ncbi.nlm.nih.gov/40869053/

“Overall, our study highlights that cannabinoids can induce significant alterations in the gut microbiota-BA axis in KPC models. The CBD-driven changes in BA metabolism and gut microbiota composition were associated with improved survival, underscoring their functional relevance. Importantly, our findings support the use of the BA–microbiota axis as a dynamic biomarker of therapeutic response to CBD in PDAC, offering a novel avenue for both mechanistic understanding and clinical monitoring.”

https://www.mdpi.com/1422-0067/26/16/7733

Comparative Effects of THC and CBD on Chemotherapy-Induced Peripheral Neuropathy: Insights from a Large Real-World Self-Reported Dataset

Posted on by

“Background/Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting adverse effect of various chemotherapeutic agents. Previous work demonstrated that cannabis alleviates symptoms of oxaliplatin-induced CIPN. To evaluate the effects of cannabis components, cannabidiol (CBD) and tetrahydrocannabinol (THC), on CIPN-related symptoms. 

Methods: We reviewed a patient-reported outcomes dataset from “Tikun Olam,” a major medical cannabis provider. Of 1493 patients, 802 reported at least one CIPN symptom at baseline, including a burning sensation, cold sensation, paresthesia (prickling) and numbness, and 751 of them met the study inclusion criteria. Patients were categorized into THC-high/CBD-low and CBD-high/THC-low groups. Symptom changes after six months of cannabis use were analyzed using K-means clustering and logistic regression, incorporating interactions between baseline symptoms and THC and CBD doses. Linear regression assessed changes in activities of daily living (ADL) and quality of life (QOL). 

Results: Both groups reported symptom improvement. The THC-high group showed significantly greater improvement in burning sensation and cold sensation (p = 0.024 and p = 0.008). Improvements in ADL and QOL were also significantly higher in the THC group (p = 0.029 and p = 0.006). A significant interaction between THC and CBD was observed for symptom improvement (p < 0.0001). 

Conclusions: Cannabis effectively reduces CIPN symptoms and improves QOL and ADL. Higher THC doses were more effective than lower doses, with combined CBD and THC doses yielding greater symptom relief.”

https://pubmed.ncbi.nlm.nih.gov/40868175/

“Cannabis products demonstrated efficacy in alleviating symptoms associated with CIPN and resulted in a reduction in the number of reported symptoms. Improvements in symptoms and in QOL and ADL questionnaire responses were observed when queried after six months of cannabis use. Higher doses of THC showed greater efficacy than lower doses, while gradually increasing doses of both CBD and THC alone and in combination correlated better with symptom improvement.

The observed dose–response relationship of both THC and CBD highlights the need for prospective controlled trials to establish optimal cannabinoid ratios for specific symptom clusters, such as burning or cold sensations. Future studies should also aim to evaluate the long-term safety and efficacy of cannabis in oncology patients, as well as explore mechanistic pathways linking cannabinoid receptor activation to neuroprotection and anti-inflammatory effects in CIPN.

Personalized treatment strategies, incorporating cannabinoid pharmacogenetics and symptom-driven dose titration, should be further investigated to better integrate medical cannabis into standard supportive oncology care.”

https://www.mdpi.com/2227-9059/13/8/1921

Benefits and Burdens of Vaporized Botanical Cannabis Flower Bud for Cancer-Related Anorexia: A Qualitative Study of the Experiences of People with Advanced Cancer Enrolled as Inpatients in a Phase I/IIb Clinical Trial and Their Family Carers

Posted on by
pubmed logo

“Background: Clinical trials are underway of medicinal cannabis for cancer-related anorexia, using various formulations and modes of administration. 

Objectives: To explore the benefits and burdens of vaporized medicinal cannabis flower bud for anorexia from the perspectives of trial participants with advanced cancer and their carers. 

Design: People with advanced cancer enrolled as inpatients in a Phase I/IIb clinical trial, and their carers participated in face-to-face semi-structured interviews. Analysis used the framework method. 

Setting: Inpatient specialist palliative care. 

Results: Ten out of 12 trial participants and 6 carers were interviewed. All perceived benefits to eating but, in two cases, this arose from reduced nausea rather than appetite stimulation. Carers sometimes perceive more benefit than patients. Psychoactive effects were well-tolerated and even enjoyed. Burdens included throat irritation and adverse smell and taste, but these were transient. 

Conclusions: Vaporized flower bud warrants comparison with other formulations/modes of medicinal cannabis for cancer-related anorexia.”

https://pubmed.ncbi.nlm.nih.gov/40865547/

Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment

Posted on by
pubmed logo

“Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge.

Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC.

This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies.”

https://pubmed.ncbi.nlm.nih.gov/40864738/

“This review explores the molecular rationale for combining CBD with EGFR TKIs in the treatment of HNSCC. Despite promising preclinical evidence demonstrating CBD’s anticancer and immunomodulatory effects, no clinical data currently support its use as an adjunct to EGFR-TKIs in HNSCC; thus, this remains a hypothesis requiring further investigation.

Significant knowledge gaps exist regarding how CBD interacts with dysregulated signaling pathways in HNSCC in the presence and absence of an EGFR-TKI. Future research should focus on elucidating these mechanisms through rigorous in vitro and in vivo studies.

Testing this hypothesis is critical, as combining CBD with EGFR-TKIs could lay a transformative foundation for significantly enhancing treatment efficacy and patient outcomes in HNSCC, potentially converting a suboptimal targeted therapy into a highly effective therapeutic strategy. Further research is warranted to establish greater confidence in supporting experimental and clinical correlative data and address key gaps in current knowledge.”

https://www.mdpi.com/1467-3045/47/8/584

Folate-chitosan nanoparticle delivery of cannabidiol for targeted triple-negative breast cancer therapy

Posted on by

“Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options. Cannabidiol (CBD) has demonstrated anticancer potential, but its clinical application is hindered by poor solubility and nonspecific distribution. This study aimed to develop a folic acid-modified chitosan (FA-CS) nanoparticle system to enhance the targeted delivery and therapeutic efficacy of CBD against TNBC.

Methods: FA-CS@CBD nanoparticles were synthesized and characterized for morphology, size distribution, zeta potential, and stability. Their in vitro anticancer effects were evaluated through cytotoxicity, cellular uptake, apoptosis, and reactive oxygen species (ROS) assays in 4T1 breast cancer cells. The in vivo antitumour efficacy and systemic toxicity were assessed using a TNBC mouse model.

Key findings: FA-CS@CBD nanoparticles exhibited uniform morphology, stable physicochemical properties, and efficient cellular uptake. Compared to free CBD, the nanoparticles significantly enhanced ROS production, induced apoptosis, and inhibited migration in 4T1 cells. In vivo studies demonstrated strong tumour-targeting capability and a tumour inhibition rate of 68.07%, with minimal systemic toxicity.

Conclusions: The FA-CS@CBD nanoparticle system improved the targeted delivery and therapeutic effects of CBD against TNBC while maintaining favorable biocompatibility. These findings highlight the potential of FA-CS-based nanocarriers for enhancing CBD clinical application in breast cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/40838692/

https://academic.oup.com/jpp/advance-article-abstract/doi/10.1093/jpp/rgaf072/8239116?redirectedFrom=fulltext&login=false

Neolignans isolated from industrial hemp (Cannabis sativa L.) roots have cytotoxic effects on cancer cells

Posted on by

“Background: The 2018 Farm Bill states that cultivars of Cannabis sativa L. (industrial hemp) are legal for industrial use if total tetrahydrocannabinol (THC) concentrations are less than 0.30%. Due to this legislation, hemp cultivars with low total THC have found a wide range of uses, from animal feed to paper production. Although cannabinoids are the most widely studied compounds in hemp, hemp produces numerous other compound classes as well, and these phytochemicals may have uses in the functional food and pharmaceutical industry.

Methods: Initial liquid chromatography profiling of hemp root samples revealed a group of uncharacterized peaks, and these peaks were tentatively identified as neolignans by Oribitrap ID-X high resolution mass spectrometer. To further elucidate the structure of these neolignans, we used techniques in liquid-liquid extraction, as well as flash chromatography to isolate them in preparation for NMR analysis. We then tested their inhibitory concentration 50 (IC50) in a variety of cancer cell lines.

Results and discussion: Four neolignans were isolated from hemp roots and each differed in their molecular weight by 30 daltons. Two of the compounds were identified as dadahols A and B. We tested fractions of various purities containing neolignans against neuroblastoma cell lines CHLA15 and LAN5, hepatoblastoma cell line Hep3B, and Hodgkin’s lymphoma cell line L428. We found that semi-pure fractions containing dadahol A and/or dadahol B had the highest cytotoxic activity. We then tested pure dadahol A and dadahol B, and this revealed dadahol A exhibited the lowest IC50 values in all the cell lines.”

https://pubmed.ncbi.nlm.nih.gov/40818965/

“We report, for the first time, that dadahols, using the methodologies described herein, have antiproliferative effects. While our findings demonstrate the cytotoxic effects of hemp-derived compounds on multiple pediatric cancer cell lines, the underlying mechanisms driving these effects remain to be elucidated.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00316-5

The Role of the Endocannabinoid System in Oncology and the Potential Use of Cannabis Derivatives for Cancer Management in Companion Animals

Posted on by
pubmed logo

“The last decades of research have shown that the endocannabinoid system may be a promising therapeutic target for the pharmacological treatment of cancer in human medicine and possibly in veterinary medicine as well.

Compared with the original cells, the expression of gene encoding for receptors and enzymes belonging to the endocannabinoid system has been found to be altered in several tumor types; it has been hypothesized that this aberrant expression may be related to the course of the neoplasm as well as to the patient’s prognosis.

Several studies, conducted both in vitro and in vivo, suggest that both endo- and phytocannabinoids can modulate signaling pathways, controlling cell proliferation and survival. In the complex process of carcinogenesis, cannabinoids seem to intervene at different levels by stimulating cell death, inhibiting the processes of angiogenesis and metastasis, and regulating antitumor immunity.

Although the molecular mechanisms by which cannabinoids act are not always clear and defined, their synergistic activity with the most used antineoplastic drugs in clinical oncology is showing promising results, thus providing veterinary medicine with alternative therapeutic targets in disease control.

This review aims to summarize current knowledge on the potential role of the endocannabinoid system and exogenous cannabinoids in oncology, with specific reference to the molecular mechanisms by which cannabinoids may exert antitumor activity. Additionally, it explores the potential synergy between cannabinoids and conventional anticancer drugs and considers their application in veterinary oncology.”

https://pubmed.ncbi.nlm.nih.gov/40804975/

“Companion animals are more and more becoming considered family members, and their owners wish to offer them the same level of cure and care expected for a human being. The long life expectancy of dogs and cats is associated with new challenges: veterinary medicine must be prepared to diagnose and treat neoplastic pathology with the same high-standard procedures that are currently used in human medicine.

Chemotherapies aim to prolong as long as possible the life of companion animals affected by cancer, but several side effects can be experienced. Thus, an increasing interest in alternative and complementary treatments has arisen in the last years. Among a wide array, cannabinoids seem to be a promising tool to be included in therapeutic protocols since their administration could assist traditional chemotherapeutic agents, promoting a more successful antineoplastic effect, prolonging the prognosis, and contributing to patient well-being thanks to pain relief.

According to all the aforementioned factors, the present review aims to summarize how the endocannabinoid system and phytocannabinoids interact in the complex process of carcinogenesis, exploring current therapeutical applications and future perspectives in veterinary oncology.”

“From the above paragraphs, it can be concluded that cannabinoids show antitumor activity (decrease in tumor growth and invasiveness) in numerous cell lines and in various animal models of cancer, and that, although clinical studies conducted in human and animal patients are limited, the results obtained so far have demonstrated that cannabinoids appear to be safe and effective antineoplastic agents.

Moreover, most of the preclinical evidence currently available demonstrates that the greatest therapeutic potential of cannabinoids lies in their combination with existing chemotherapeutic drugs.

Interestingly, compared to conventional antineoplastic drugs, which have a plethora of side effects, cannabinoids (especially the non-psychoactive ones, such as CBD) have a broad safety margin. “

https://www.mdpi.com/2076-2615/15/15/2185