Category Archives: Cancer

Cannabidiol (CBD) as a novel inhibitor of HLA-G expression in human choriocarcinoma cell line (JEG-3)

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“Cannabinoids have emerged as promising agents in cancer research due to their antitumor properties. While their effects on tumor growth and survival are well documented, their influence on immune checkpoint regulation remains poorly understood.

Here, we investigated the effects of cannabidiol (CBD) and a high-CBD extract (CBD-HCE) on HLA-G expression in human choriocarcinoma JEG-3 cells, a non-classical HLA class I molecule linked to tumor immune escape.

Safe concentrations of CBD and CBD-HCE were determined by MTT assays. Apoptosis (Caspase-3), proliferation (Ki-67), and migration (wound healing and MMP-9 immunostaining) were assessed, and HLA-G expression was quantified by RT-qPCR and immunocytochemistry.

Both CBD and CBD-HCE reduced cell proliferation and migration, increased apoptosis, and significantly downregulated HLA-G expression at both the mRNA and protein levels. This inhibitory effect was dose- and time-dependent, and fully reversible after treatment withdrawal, indicating a dynamic and CBD-dependent modulation.

These results provide the first experimental evidence of HLA-G downregulation by CBD and CBD-HCE, highlighting a novel immunomodulatory mechanism with potential therapeutic implications.

By simultaneously impairing tumor viability and reversing immune evasion, CBD-based compounds may enhance antitumor immunity and potentiate immunotherapy efficacy. Further research involving additional tumor cell lines, in vivo models, and immune-relevant systems are necessary to validate and expand upon these findings.”

https://pubmed.ncbi.nlm.nih.gov/41233461/

“A great number of studies have shown that THC, CBD and other cannabinoids exhibit antitumor effects in a wide range of in vitro and in vivo cancer models.”

“Taken together, our study provides novel in vitro evidence that CBD and CBD-rich extracts inhibit tumor cell proliferation and migration while downregulating HLA-G, a critical IC molecule involved in tumor immune escape. “

https://www.nature.com/articles/s41598-025-23554-2

Cannabidiol Reprograms Glucose Metabolism in Colorectal Adenocarcinoma by Targeting HIF-1α/LDHA Pathway

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“Colon adenocarcinoma (COAD) is characterized by the metabolic reprogramming, such as the Warburg effect, which drives tumor progression and immunosuppression. Hypoxia-inducible factor 1 (HIF-1) and lactate dehydrogenase A (LDHA) are critical regulators of this metabolic shift, but existing therapies are insufficiently specific to it.

This study investigates the antitumor mechanisms of cannabidiol, a non-psychoactive phytocannabinoid, by using integrative multi-omics and functional validation.

Single-cell transcriptomics revealed that cannabidiol reduced tumor cell proportions and suppressed glycolytic activity in COAD.

Network pharmacology identified PTGS2 as a central target, with proteomic data confirming its overexpression in COAD tissues and association with poor prognosis. In vitro, cannabidiol inhibited COAD cell proliferation, migration, and colony formation while downregulating HIF-1[Formula: see text], LDHA, and GLUT1 expression.

Metabolic assays demonstrated associated dose-dependent reductions in ATP production, glucose uptake, and lactate levels. Rescue experiments using the HIF-1agonist DMOG partially reversed cannabidiol’s antiglycolytic and antitumor effects, and thus confirmed pathway dependency. Synergy with the glycolysis inhibitor 2-DG enhanced therapeutic efficacy, which highlighted cannabidiol’s potential to overcome metabolic resistance.

These findings establish cannabidiol as a novel inhibitor of HIF-1/LDHA-driven glycolysis, and thus provide a translational strategy for metabolic vulnerability in COAD.”

https://pubmed.ncbi.nlm.nih.gov/41219135/

https://www.worldscientific.com/doi/10.1142/S0192415X25500958

“The phrase “Cannabidiol Reprograms Glucose Metabolism in Colorectal Adenocarcinoma by Targeting HIF-1α/LDHA Pathway” means that cannabidiol (CBD) helps fight colon cancer cells by altering how they use glucose (sugar) for energy, specifically by interfering with a key biological pathway involving the proteins HIF-1α and LDHA.”

“In summary, the study found that CBD acts as a novel inhibitor of the HIF-1α/LDHA pathway, suppressing the abnormal glucose metabolism essential for colorectal cancer growth and providing a potential therapeutic strategy for treatment.”

Combination CBD/THC in the management of chemotherapy-induced peripheral neuropathy: a randomized double blind controlled trial

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“Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) can greatly impair function, leading to disability or truncated treatment in cancer patients. Previous animal studies show that cannabidiol (CBD) and delta-9- tetrahydrocannabinol (THC) can ameliorate CIPN. This study assessed the effect of combined CBD and THC on CIPN symptoms amongst cancer patients treated with taxane- or platinum-based agents.

Materials and methods: This 12-week randomized, double-blind, placebo-controlled trial included participants with nonmetastatic breast, colorectal, endometrial, or ovarian cancer experiencing grade 2-3 CIPN. The active group received CBD (125.3-135.9 mg) combined with THC (6.0-10.8 mg) in gelcaps. The Quality-of-Life Questionnaire-CIPN twenty-item scale (QLQ-CIPN20) sensory subscale was used as the primary outcome. Additional outcomes assessed pain, sleep, and function. Neurologic exams evaluated touch, pressure, and vibration sense. Following the randomized controlled trial, participants were invited to enroll in a 12-week open-label observational study.

Results: Of 230 participants identified, 124 met eligibility, 54 were enrolled, 46 were randomized, and 43 completed 12 weeks of treatment. This was lower than our goal of 100 randomized participants. The mean age was 60 +/- 9 years, 88% were female, 63% had breast cancer. All participants had completed chemotherapy. The primary analysis showed no differences in outcome measures between active and placebo groups, likely due to sample size. Although an increase in bilirubin (one participant in active group, and one in placebo) and alkaline phosphatase (one participant in active group) was seen, this did not exceed the exit criteria. A secondary analysis showed that the active group experienced greater improvement in the QLQ-CIPN20 measures of sensory impairment relative to placebo (-10.4 (95% -20.5, -0.3), p = 0.044). There was also improvement in light touch and vibration sensation of the feet on neurological exam that approached significance. There was no effect on other measures, including pain, and no between-group differences in side effects. The uncontrolled observational study showed similar results.

Discussion: The primary analysis showed no between-group difference in CIPN symptoms. The secondary analysis indicated that CBD with THC could improve sensory impairment and might increase touch and vibration sense, although these findings require confirmation in a future, more fully powered study. Nonetheless, our results show that combination CBD/THC can be safely delivered to participants with CIPN and suggest that these cannabinoids should be further investigated for this indication.”

https://pubmed.ncbi.nlm.nih.gov/41211445/

“Overall, this study suggests that combination CBD/THC could help with the sensory impairment seen in CIPN. Since the disorder is prevalent and incurs significant hardship, even a modest sensory improvement could enhance patients’ quality of life, given the lack of alternatives.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1590168/full

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