Cannabidiol sensitizes triple-negative breast cancer cells to NK cell-mediated killing via EGFR inhibition and FAS upregulation

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“Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype lacking targeted therapies, presenting a significant clinical challenge. The epidermal growth factor receptor (EGFR) plays a crucial role in TNBC progression, making it a promising target for therapeutic intervention. This study investigated the potential of cannabidiol (CBD) as a therapeutic agent that targets EGFR and associated signaling pathways in TNBC.

Methods: The TNBC cell lines MDA-MB-468 and MDA-MB-231 were treated with CBD in the presence or absence of epidermal growth factor (EGF). Cell proliferation, FAS protein expression, and activation of the EGFR signaling pathway were assessed. The cytotoxic effects of CBD on TNBC cells and natural killer (NK) cells were also evaluated.

Results: CBD significantly elevated FAS protein expression in MDA-MB-468 cells compared to EGF treatment alone (125.29 ± 5.87% vs. 83.07 ± 1.30%, p < 0.0001). Further molecular analysis revealed that CBD inhibited EGFR signaling by downregulating key oncogenic proteins, including KRAS, PI3K, and AKT. Moreover, CBD enhanced the cytotoxic effects of NK-92 cells, reducing the viability of MDA-MB-468 cells more effectively than EGF alone did (52.12 ± 1.28% vs. 113.69 ± 1.68%, p < 0.0001).

Conclusions: These findings suggest that CBD holds promise as a potential anticancer agent in TNBC by disrupting EGFR signaling and promoting apoptosis. However, further studies are necessary to optimize its therapeutic window and minimize adverse effects, particularly regarding its potential cytotoxicity to immune cells.”

https://pubmed.ncbi.nlm.nih.gov/41188939/

“Our findings underscore the therapeutic potential of CBD in TNBC by targeting EGFR-driven pathways, modulating FAS expression, and enhancing immune-mediated killing. This study offers renewed hope for patients facing this challenging disease, positioning CBD as a potentially potent and multifaceted therapeutic agent.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00340-5

Measuring the Effects of Cannabis on Anxiety and Depression Among Cancer Patients

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“Introduction: Cancer patients are increasingly turning to cannabis products to modulate physical and psychological symptoms despite limited evidence supporting their efficacy. We aimed to explore cancer patients’ self-reported anxiety and depression symptoms in response to cannabis use.

Methods: This longitudinal study examined how patient-reported anxiety and depression symptoms varied according to the dose, ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD), and route of administration of cannabis products among cancer patients. Change in self-reported anxiety and depression symptoms was evaluated in 1962 cancer patients after 30 days of enrollment in the Minnesota Medical Cannabis Program.

Results: Anxiety scores improved more in patients taking higher doses of CBD (> 14.3 mg/day) compared to those taking lower doses (< 4.6 mg/day) and among patients using enteral cannabis products. Depression scores also improved more for patients taking enteral products.

Discussion: Anxiety scores varied according to the dose of cannabis, the ratio of THC to CBD, and the route of administration of cannabis products. In contrast, depression scores only varied according to the route of administration.

Conclusions: This study of cancer patients in Minnesota suggests that patterns of cannabis use that include relatively higher doses of CBD taken enterally may improve the quality of life of cancer survivors who report anxiety and depression. This study constructs a foundation for future research to improve the tailoring of cannabis-related educational materials to patients’ needs and inform the training of healthcare professionals on how to recommend cannabis products for cancer survivors.”

https://pubmed.ncbi.nlm.nih.gov/41163433/

“Given the high prevalence of anxiety and depression symptoms among cancer patients, along with the potential for cannabis products to alleviate these serious psychological symptoms, this study suggests specific patterns of use that may improve the quality of life of cancer survivors.”

https://onlinelibrary.wiley.com/doi/10.1002/cam4.71342

Phytochemical Profile, Extraction and Characterization of Bioactive Compounds from Industrial Hemp (Cannabis sativa L.) Felina 32 Variety

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“An efficient method for the simultaneous extraction of cannabinoids and terpenes from the leaves and flowers of Cannabis sativa L. (var. Felina 32) was developed.

Extraction parameters, including solvent type, temperature, and pressure, were optimized, revealing that hexane enables high-yield cannabinoid recovery. Moreover, terpene composition was influenced by the extraction temperature. Two extracts with the highest cannabinoid content were selected for further study, Feli1 (64.76%) and Feli2 (61.32%), both obtained using hexane. Feli1, extracted at -55 °C, had a monoterpene-to-sesquiterpene ratio of 16.7% to 83.3%, while Feli2, extracted at 25 °C, showed a higher monoterpene content (25.2%) and lower sesquiterpene content (74.8%).

Both extracts demonstrated selective antiproliferative activity against cancer cell lines, with reduced toxicity toward normal breast epithelial cells (MCF-10A). Feli2 showed slightly stronger antiproliferative effects, likely due to its higher monoterpene content. At low concentrations, both extracts stimulated the growth of MV4-11 leukemia and MDA-MB-468 triple-negative breast cancer (TNBC) cells, while higher concentrations led to growth inhibition. These stimulatory effects were weaker than those observed for pure Δ9-THC or CBD.”

https://pubmed.ncbi.nlm.nih.gov/41157165/

https://www.mdpi.com/1420-3049/30/20/4148

Cannabidivarin directly targets the immunosuppressive activity of regulatory myeloid cells in tumors

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“Immunosuppression within the tumor microenvironment (TME) is a major obstacle for effective cancer immunotherapy. This is largely driven by myeloid suppressor cells, specifically Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs), which create an environment that inhibits the immune response. The presence of these cells is strongly correlated with poor patient outcomes and resistance to treatment, highlighting the need for new strategies to mitigate their effects.

In this study, we investigated the therapeutic potential of Cannabidivarin (CBDV), a less-studied non-psychoactive cannabinoid, to reprogram these immunosuppressive cells.

We found that CBDV directly targets myeloid suppressor cells, significantly impairing their immunosuppressive function both in vitro and in vivo. Mechanistically, CBDV reduces the key immunosuppressive markers inducible, Nitric Oxide Synthase (iNOS) and Arginase-1 (Arg-1) in murine MDSCs and promotes the differentiation of TAMs into M1-like macrophages.

This shift in myeloid cell function leads to restored CD8 + T-cell proliferation and activation. Furthermore, our results show that CBDV treatment in tumor-bearing mice reduces tumor progression and improves the anti-tumor immune response within the TME. We also confirmed the clinical relevance of our findings, demonstrating that CBDV effectively reduces the immunosuppressive phenotype of human-derived myeloid cells.

Altogether, these results establish CBDV as a new immunotherapeutic agent that directly neutralizes myeloid suppressor cells, thereby enhancing the immune system’s response against cancer.”

https://pubmed.ncbi.nlm.nih.gov/41151304/

“Our findings showcase the vast potential of CBDV in improving the success rate of cancer treatment.”

https://www.sciencedirect.com/science/article/pii/S0753332225008911?via%3Dihub

The potential role of cannabidiol (CBD) in lung cancer therapy: a systematic review of preclinical and clinical evidence

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“Background: Lung cancer is one of the most prevalent and lethal cancers worldwide, with limited therapeutic options in advanced stages. Cannabinoids have recently attracted attention as potential anticancer agents; however, cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has emerged as the most promising candidate. Unlike Δ9-tetrahydrocannabinol (THC), CBD lacks psychoactive properties, is generally well tolerated, and demonstrates a favorable safety profile. Moreover, CBD influences multiple cancer-relevant pathways-including apoptosis, epithelial-to-mesenchymal transition (EMT), and immune modulation-that are particularly relevant to non-small cell lung cancer (NSCLC). These features provide a strong rationale for focusing on CBD in lung cancer therapy.

Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, using defined keywords such as “CBD,” “lung cancer,” and “non-small cell lung cancer.” Studies from 2007 to 2025 were screened following PRISMA guidelines, and 19 studies met the inclusion criteria.

Results: Nineteen studies met the inclusion criteria, comprising 13 in vitro studies, 4 in vivo animal studies, and 2 clinical reports. Across these studies, CBD was administered at concentrations ranging from low micromolar levels (1-10 µM) in cell-based experiments to oral doses of 200-600 mg/day in human cases. Mechanistically, CBD induced apoptosis through pathways such as PPAR-γ activation, mitochondrial dysfunction, and oxidative stress. It inhibited epithelial-to-mesenchymal transition (EMT), downregulated invasive markers, and modulated the tumor microenvironment by enhancing CD8 + T cell and NK cell activity. Furthermore, CBD showed synergistic effects with conventional therapies (e.g., cisplatin, radiotherapy) by increasing drug uptake and overcoming resistance.

Conclusions: CBD holds promise as an adjunct in lung cancer therapy, addressing key cancer hallmarks such as tumor growth, metastasis, and treatment resistance. While preclinical evidence is robust, clinical trials remain limited. Future research should focus on optimizing dosing regimens, evaluating long-term safety, and validating these findings in large-scale human studies.”

https://pubmed.ncbi.nlm.nih.gov/41126219/

“Cannabidiol (CBD) demonstrates strong preclinical activity against lung cancer, targeting multiple hallmarks of cancer including apoptosis induction, suppression of EMT and metastasis, modulation of immune responses, and sensitization to chemotherapy and radiotherapy.”

https://cancerci.biomedcentral.com/articles/10.1186/s12935-025-04010-7

Survival rate of patients with combined hepatocellular cholangiocarcinoma receiving medical cannabis treatment: A retrospective, cohort comparative study

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“Background: Cholangiocarcinoma (CCA) incidence in Northeastern Thailand is very high and a major cause of mortality. CCA patients typically have a poor prognosis and short-term survival rate due to late-stage diagnosis. Thailand is the first Southeast Asian country to approve medicinal cannabis treatment, especially for palliative care with advanced cancer patients.

Methods: A retrospective cohort study compared survival among 491 newly diagnosed advanced CCA patients between September 2019 and June 2021. Of these, 404 received standard palliative pain management (ST), and 87 received medicinal cannabis treatment (CT). Patients were enrolled from four tertiary hospitals and two secondary hospitals in five provinces of Northeast Thailand. Cumulative survival was calculated by the Kaplan-Meier method, and independent prognostic factors were analyzed using Cox regression.

Results: For ST patients, follow-up time was 790 person-months, with a mortality rate of 48.35/100 person-months. For CT patients, follow-up time was 476 person-months, with a mortality rate of 10.9/100 person-months. The median survival time after registration at a palliative clinic was 0.83 months (95% CI: 0.71-0.95) for ST and 5.66 months (95% CI: 1.94-9.38) for CT. Multivariate analysis showed CT was significantly associated with prolonged survival (HRadj = 0.28; 95% CI: 0.20-0.37; p < 0.001).

Conclusions: The medical cannabis increased overall survival rates among CCA patients. In this retrospective cohort, Medicinal cannabis treatment was associated with more prolonged survival among advanced CCA patients in Northeastern Thailand. While this association remained significant after multivariable adjustment, unmeasured or residual confounding factors may have influenced the observed outcomes. Although the association remained significant after adjustment, unmeasured or residual confounders may have influenced outcomes. Further prospective studies are warranted to confirm these findings and explore potential mechanisms.”

https://pubmed.ncbi.nlm.nih.gov/41113085/

https://f1000research.com/articles/11-1212/v3

Cannabis Laws and Opioid Use Among Commercially Insured Patients With Cancer Diagnoses

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“Importance: Pain is a prevalent cancer-related symptom, but limited research investigates whether cannabis is an effective analgesic for cancer pain.

Objective: To examine the association of medical and recreational cannabis dispensary availability on prescription opioid dispensing among commercially insured patients with cancer.

Design, setting, and participants: This cross-sectional study used synthetic control to investigate the association of cannabis dispensary openings with pain medication dispensing among patients with cancer. Data were extracted from Optum’s deidentified Clinformatics Data Mart database from January 1, 2007, to December 31, 2020. The study population included patients aged 18 to 64 years with a cancer diagnosis and at least 6 months of continuous enrollment. Associations were estimated by age, race and ethnicity, and sex. Data were analyzed between December 2024 and February 2025.

Exposures: Exposures included indicators for whether a medical or recreational cannabis dispensary was open in each state-quarter.

Main outcomes and measures: The outcome measures for opioids prescriptions were (1) the rate of patients with a prescription per 10 000 patients, (2) the quarterly mean days’ supply per prescription, and (3) the quarterly mean number of prescriptions per patient.

Results: The study included a mean (SD) of 3.05 (0.86) million patients annually across the US (mean [SD] age, 43.7 [9.6] years; mean [SD] 59.0% [0.32%] female). Medical cannabis dispensary openings were associated with significant reductions in all opioid outcomes. The rate of patients with cancer with opioid prescriptions changed by -41.07 per 10 000 (95% CI, -54.78 to -27.36 per 10 000; P < .001), the quarterly mean days’ supply by -2.54 days (95% CI, -3.16 to -1.92 days; P < .001), and the mean number of prescriptions per patient by -0.099 (95% CI, -0.121 to -0.077; P < .001). Recreational dispensary openings were also associated with reductions in opioid outcomes, though estimated treatment effects were smaller. The rate of prescriptions changed by -20.63 per 10 000 (95% CI, -35.35 to -5.91 per 10 000; P = .049), the mean daily supply by -1.09 days supplied per prescription (95% CI, -1.72 to -0.46 days; P = .04), and the mean number of prescriptions per patient by -0.097 (95% CI, -0.134 to -0.060; P = .01).

Conclusions and relevance: This study’s findings indicate cannabis may be a substitute for opioids in the management of cancer-related pain. However, further research directly observing cannabis use is needed to evaluate the efficacy of cannabis as a treatment for cancer-related pain.”

https://pubmed.ncbi.nlm.nih.gov/41105418/

“These findings indicate that medical or recreational cannabis laws may be significantly associated with reduced opioid use among patients diagnosed with cancer.”

https://jamanetwork.com/journals/jama-health-forum/fullarticle/2840030

Advancing cervical cancer treatment: integrating cannabinoids, combination therapies and nanotechnology

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“Background: Cervical cancer remains a major global health challenge, with the highest incidence and mortality rates observed in sub-Saharan Africa. Despite progress in prevention and treatment, the management of advanced and recurrent disease remains difficult.

Aim: This review explores the potential role of cannabinoids in cervical cancer therapy, with a focus on their integration into existing treatment strategies, combination therapies, and nanotechnology-based delivery systems.

Methods: A critical synthesis of preclinical studies and emerging therapeutic approaches was conducted, examining the anticancer properties of cannabinoids, their mechanisms of action, and their application within combination and nanotechnology-based treatment modalities.

Results: Cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) demonstrate anticancer effects by inducing apoptosis, inhibiting cell proliferation, and suppressing metastasis. Mechanistic studies highlight their ability to promote oxidative stress, modulate key signalling pathways, and influence immune responses in cervical cancer cells. Combination therapies involving cannabinoids with chemotherapy, radiotherapy, and immunotherapy show enhanced efficacy and reduced drug resistance. Furthermore, nanotechnology-based delivery systems offer advantages including targeted drug release, improved solubility, controlled dosing, and decreased systemic toxicity.

Conclusion: Cannabinoids represent a promising adjunct in cervical cancer management. However, successful clinical translation requires optimisation of formulations, establishment of dosing protocols, and comprehensive safety evaluation. Future research should also explore biomarker-driven personalised medicine approaches. Standardisation, along with addressing regulatory and ethical challenges, will be crucial for the integration of cannabinoid-based therapies into mainstream cervical cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/41102423/

“The convergence of cannabinoids, nanotechnology, and combination therapies presents a promising frontier in cervical cancer treatment. This approach leverages the synergistic potential of cannabinoids with conventional treatments such as chemotherapy, radiotherapy, and immunotherapy, while using nanotechnology for targeted delivery. The integration of these elements could enhance treatment efficacy and minimize side effects.”

https://link.springer.com/article/10.1007/s00432-025-06323-6

Synergistic combination of cannabidiol and celecoxib or 2,5-dimethylcelecoxib exerts oxidative stress-mediated cytotoxicity and mitigates glioblastoma invasiveness

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“Glioblastoma remains one of the most aggressive and treatment-resistant malignancies. Current treatment options, such as radio- and chemotherapy, induce oxidative stress-mediated DNA damage leading to cancer cell death, but are also neurotoxic and not efficient in long term.

Our study investigated the effects of cannabidiol, celecoxib and 2,5-dimethylcelecoxib, individually and in combinations, on U-138 MG glioblastoma cell survival, oxidative stress, canonical and non-canonical Nrf2 pathway activation, cell migration and apoptosis.

Using the MTT and flow cytometry assay we found that the analyzed compounds and their combinations induce dose-dependent, synergistic, and oxidative stress-related cytotoxicity, with minimal impact (at the concentrations exhibiting anti-cancer effects) on non-cancerous human astrocyte (HA) cell line.

The Nrf2 ELISA assay was used for the analysis of the nuclear binding of the nuclear factor-2 erythroid related factor-2 (Nrf2), which followed by the RT-qPCR and Western blot analysis, confirmed the antioxidant response of cells to the applied treatments. Diminished migratory potential, and increase of the autophagy-related p62, LC3 and apoptosis-related caspase-3 protein levels were also observed in response to the treatment with the analyzed compounds.

Overall, our study provides evidence that cannabidiol combined with celecoxib or 2,5-dimethylcelecoxib may represent a promising strategy for glioblastoma treatment.”

https://pubmed.ncbi.nlm.nih.gov/41089524/

“In conclusion, the combination of CBD with celecoxib or 2,5-DMC represents a promising therapeutic strategy for glioblastoma. While CBD alone induces cytotoxicity, ROS production, and apoptosis, our synergy analysis demonstrates that combining CBD with celecoxib or 2,5-DMC allows effective killing of GBM cells at lower CBD concentrations. “

https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2025.15062/full

Bioinformatics differential expression analysis of the effect of cannabidiol in chronic myeloid leukaemia cell line

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“Chronic myeloid leukaemia (CML) is the first clonal myeloproliferative disorder of pluripotent stem cells to be associated with a specific genetic abnormality, the Philadelphia chromosome, bearing the BCR-ABL1 fusion oncogene. Tyrosine kinase inhibitors are used as first-line treatment for the chronic phase of CML, although alternative treatments are necessary for resistant cases.

Cannabidiol (CBD) is a major constituent of hemp oil that exerts a broad range of pharmacological effects in various malignancies. However, its molecular mechanisms in leukaemia remain unclear. In the present study, Imatinib-sensitive K-562S cells were subjected to CBD treatment (IC50: 17.69 μM) for 4 and 12 h, followed by RNA sequencing to identify differentially expressed genes (DEGs).

The subsequent transcriptomic profiling revealed 3518 DEGs at 12 h and 3433 DEGs at 4 h of treatment, including significant modulation of metallothionein-regulated oxidative stress responses (MT1MT2, and SLC30A2) and p53-mediated apoptosis (TP53TG3DDIT4BBC3CHAC1NOXA1, and DAPK2). Additionally, the DEGs were enriched in alterations in immune signalling pathways-including type I interferon activation and PI3K-Akt-mTOR and Toll-like receptor signalling-crucial in leukaemia progression, as well as variations in lipid metabolism and mitochondrial homeostasis.

The results presented in this study validate the considerable potential of CBD to induce broad transcriptional and signalling alterations, related to immune modulation, apoptosis, and metabolic processes in K-562S cells. These findings provide novel insights into the therapeutic potential of CBD and lay the groundwork for further investigation into its precision applications in haematological malignancies.”

https://pubmed.ncbi.nlm.nih.gov/41080716/

“Cannabis sativa (marijuana, hashish) has been used for centuries as an herbal remedy for the treatment of various ailments, as well as for its psychotropic properties. More than 550 constituents have been identified in cannabis, of which greater than 100 are represented by the family of phytocannabinoids. The most abundant amongst them are the psychoactive Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which exhibit primary anti-cancer effects on various malignant diseases, including leukaemia.”

https://www.sciencedirect.com/science/article/pii/S2699940425000773?via%3Dihub