Category Archives: Cancer

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

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“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

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“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

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“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

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“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

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“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

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“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

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“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

Cannabichromene: integrative modulation of apoptosis, ferroptosis, and endocannabinoid signaling in pancreatic cancer therapy

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“Cannabichromene (CBC: C21H3O2, M.W.: 314.46 g) is a non-psychotropic phytocannabinoid derived from Cannabis sativa (hemp), and its potential therapeutic properties have attracted increasing attention. Specifically, it has demonstrated strong anti-inflammatory effects in animal models of edema through non-CB receptor mechanisms; however, further pharmacological studies based on cancer models are required.

In this study, we investigated the molecular mechanisms underlying the anti-cancer activity of CBC in human pancreatic cancer cells.

Through mRNA-seq analysis, the expression levels of many genes involved in cell death pathways were upregulated or downregulated after CBC treatment, and these included ferroptosis-related genes, such as HMOX1. We further confirmed the functional validity of apoptosis and ferroptosis induction after CBC treatment using various molecular assays. In addition, CBC preferentially increased the expression of TRPV1 and CB2.

Accordingly, the effects on cell death were reversed after treatment with TRPV1 and CB2 inhibitors, suggesting that receptor expression is necessary for the induction of apoptotic cell death. Finally, we confirmed the consistent regulation of apoptosis, ferroptosis, and endocannabinoid receptors during tumor growth inhibition after CBC treatment using in vivo xenograft models.

Therefore, we propose that CBC exhibits pharmacological activity via the integrative modulation of multiple cell death pathways, which can be exploited for pancreatic cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/40790027/

“Cannabinoids extracted from Cannabis sativa exert their effects by binding to specific receptors that play a role in tissue development and homeostasis maintenance in the human body.”

“CBC treatment induces apoptotic cell death in pancreatic cancer cells”

“Our current study demonstrates that CBC modulates multiple forms of cell death by regulating the expression of proteins involved in both apoptotic and ferroptotic pathways. Although CBC-induced apoptosis was dependent on TRPV1 and CB2 receptors, the ferroptotic pathway appeared to be independent of these receptors.

Accordingly, we propose that CBC exerts its pharmacological effects through the integrative modulation of multiple cell death pathways, which could offer therapeutic benefits for pancreatic cancer treatment.

These results enhance our understanding of how CBC induces diverse cell death mechanisms via ECS receptors, not only in pancreatic cancer but also in other cancer models.

This study provides a promising foundation for the development of cannabinoid-based anti-cancer drugs, offering a new strategy for targeting various types of cancer through the modulation of apoptosis and ferroptosis.”

https://www.nature.com/articles/s41420-025-02674-8

Recent Advances in the Therapeutic Potential of Cannabinoids Against Gliomas: A Systematic Review (2022-2025)

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“Glioma is the most common and lethal primary brain tumor in adults, with glioblastoma (GBM) representing the most aggressive subtype, characterized by diffuse infiltration, resistance to therapy, and a poor prognosis. Despite standard treatments, survival remains only approximately 14 months.

Cannabinoids have been increasingly investigated for their therapeutic potential in gliomas, particularly GBM. Although multiple reviews on this field of research have been published, most are current only up to 2022. This systematic review aims to provide an updated summary of studies published between 2022 and 2025, capturing recent developments in anti-glioma mechanisms, combinational strategies, immune modulation, and novel therapeutic platforms.

Following PRISMA guidelines, PubMed, Scopus, ScienceDirect, and SpringerLink were searched for original English-language journal articles published between January 2022 and February 2025, using search terms related to cannabinoids and brain cancer. From 1031 records, 45 original research articles were included after removing duplicates, non-primary studies, and irrelevant topics. The studies were categorized into seven thematic domains based on content.

Recent studies have elaborated on the anti-cancer mechanisms of cannabinoids beyond endocannabinoid signaling via the CB1/CB2 receptor, including ferroptosis induction, mitochondrial dysfunction, integrated stress response activation, and epigenetic modulation. Synthetic cannabinoids and their analogs demonstrated enhanced blood-brain barrier penetration and cytotoxicity in glioma models.

Cannabinoids have been shown to modulate immune responses in glioma, influencing T cell infiltration, myeloid suppressor cell recruitment, and tumor-associated macrophage function. Novel formulation and delivery strategies have improved cannabinoid solubility, stability, and tumor targeting. Combination therapies, particularly cannabidiol with temozolomide or radiotherapy, exhibited additive or synergistic anti-tumor effects, although variability between glioma subtypes suggests the need for personalized approaches.

Although cannabinoid-based glioma research has expanded our understanding of the mechanisms, discrepancies between preclinical findings and clinical data highlight the need for rigorous clinical trials and mechanistic research before cannabinoid-based treatments can be reliably integrated into standard glioma care.”

https://pubmed.ncbi.nlm.nih.gov/40781861/

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.70160

Cannabidiol Suppresses EMT in Pancreatic Cancer via Inhibition of MALAT1 lncRNA and PI3K/Akt/mTOR Signaling Pathway

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“Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive metastasis and poor response to chemotherapy, largely driven by epithelial-mesenchymal transition (EMT) and chemokine signaling.

Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has shown anticancer potential, yet its mechanisms in EMT regulation remain underexplored in PDAC.

In this study, we demonstrate that CBD significantly suppresses the expression of CXCR4/CXCR7 and matrix metalloproteinases (MMP-2/9), leading to reduced migration and invasion of MIA PaCa-2, PANC-1, and AsPC-1 cells. Moreover, CBD reversed CXCL12-induced EMT by downregulating mesenchymal markers and restoring epithelial markers. Mechanistically, CBD inhibited the expression of the long non-coding RNA MALAT1, a known EMT regulator, and antagonized its pro-invasive effects. Overexpression of MALAT1 activated the PI3K/Akt/mTOR pathway and enhanced EMT-related protein expression, all of which were effectively reversed by CBD. Furthermore, the combination of CBD and gemcitabine exhibited synergistic inhibition of MALAT1, EMT markers, and PI3K/Akt/mTOR signaling without inducing cytotoxicity, suggesting a therapeutic advantage.

Collectively, these findings reveal a novel mechanism through which CBD impedes PDAC metastasis and underscore its promise as a complementary agent in chemotherapy regimens.”

https://pubmed.ncbi.nlm.nih.gov/40767250/

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has garnered considerable interest in oncology for its anti-inflammatory, pro-apoptotic, and anti-metastatic properties.”

“CBD has garnered increasing interest in oncology due to its multifaceted anticancer properties.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/iub.70042