Category Archives: Cancer

Dual-Function Plant-Derived Nanovesicles From Regenerated Cannabis sativa Roots for Immunotherapy and Vaccine Delivery

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“Cannabis sativa is a medicinal plant that produces a diverse array of pharmacologically active metabolites, making it a valuable resource for pharmaceutical applications.

In this study, an adventitious root (AR) culture system was established from C. sativa using two representative plant growth regulators-naphthaleneacetic acid (NAA; hereafter referred to as N-ARs) and indole-3-butyric acid (IBA; hereafter referred to as I-ARs) -from which plant-derived nanovesicles (PDNVs) were subsequently isolated (hereafter N-PDNVs and I-PDNVs, respectively).

The resulting N-PDNVs and I-PDNVs exhibited average diameters of 128 ± 2 and 124 ± 4 nm, respectively, with zeta potentials of -12.9 and -15.7 mV. Both PDNV types maintained structural integrity and colloidal stability under diverse external stress conditions, underscoring their physicochemical robustness. Metabolite profiling of PDNVs revealed 25 distinct metabolites. Functionally, I-PDNVs markedly enhanced dendritic cell maturation through Toll-like receptor 2 (TLR2)- and TLR4-dependent pathways, promoted T cell proliferation and activation (notably IFN-γ- and IL-17A-producing subsets), and increased natural killer (NK) cell activity compared with N-PDNVs.

In immunosuppressed and tumour-bearing mouse models, I-PDNVs further augmented NK cell, Th1 and cytotoxic T lymphocyte (CTL) responses, thereby confirming their superior potential as immunotherapeutic agents. Moreover, in immunized mouse models, OVA257-264-encapsulated I-PDNVs demonstrated a clear advantage as a vaccine delivery platform by eliciting a potent OVA257-264-specific CTL response.

When applied as a prophylactic cancer vaccine, they not only delayed tumour growth but also reshaped the antitumour immune landscape, characterized by enhanced CTL responses, reduced regulatory T cell frequencies and diminished exhausted CD8⁺ T cell populations.

Collectively, these findings highlight the potential of I-PDNVs as dual-function PDNVs, serving both as immunotherapeutic agents and as vaccine delivery platforms for applications requiring reinforced Th1, CTL and NK cell responses.”

https://pubmed.ncbi.nlm.nih.gov/41316982

“Nanovesicles, commonly referred to as extracellular vesicles (EVs) are secreted by various organisms or are artificially isolated under various conditions, with their sizes ranging from 30 nm to 10 µm. Owing to their functional properties, such as immunity promotion, inflammation control and antioxidant activities, nanovesicles have attracted attention as promising candidates for drug delivery systems (DDS) and for treating various immune-related diseases, including cancers, infectious diseases and autoimmune disorders.”

“Our study is the first to report the differences in the metabolic properties and immunoenhancing efficacy between I-PDNVs and N-PDNVs isolated from C. sativa AR induced by two distinct plant hormones, IBA and NAA. I-PDNVs strongly promoted a Th1-biased immune response by inducing both innate and adaptive immune activation, demonstrating their superior potential as an immunotherapeutic agent for immunosuppression and cancer treatment. Furthermore, the multifunctionality of I-PDNVs is highlighted by validating their potential as an integrated adjuvant and DDS in a cancer vaccine model.

Our findings suggest that I-PDNVs are promising immunotherapeutic candidates not only for cancer treatment, but also for intracellular infectious diseases and chronic viral infections, emphasizing their role as a multifunctional nanomaterial capable of integrating adjuvant and vaccine delivery functions for next-generation vaccine development.”

https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.70206

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

“Results of this study suggest that cannabis may serve as a substitute for opioids in managing cancer-related pain, underscoring the potential of cannabis policies to impact opioid use.”

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

Cannabidiol in Gliomas: Therapeutic Potential and Nanocarrier Strategies, with an Emphasis on Vesicular Delivery Systems

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“Cannabidiol (CBD), a nonpsychoactive phytocannabinoid extracted from Cannabis sativa, has emerged as a compound of considerable therapeutic interest across numerous medical disciplines, including pain management, anti-inflammatory therapy, and oncology.

This review critically examines the potential of CBD in the treatment of glioblastoma multiforme (GBM), one of the most aggressive and treatment-resistant primary brain tumors.

Particular emphasis is placed on the molecular mechanisms underlying CBD’s antitumor activity, including the modulation of key signaling pathways, inhibition of tumor proliferation, and enhancement of chemosensitivity. Furthermore, the review highlights the increasing role of nanotechnology in overcoming the intrinsic pharmacokinetic limitations of CBD, particularly its low oral bioavailability, which presents a significant challenge to its clinical application. Advanced nanocarrier platforms, including nanoemulsions, nanoparticles, nanoparticle-based transdermal systems, nanocapsules, and liposomes, have shown promise in optimizing CBD delivery to the central nervous system (CNS).

Notably, the integration of CBD into lipid-based drug delivery systems (LBDDS) is highlighted as a particularly promising strategy to potentiate its therapeutic efficacy. This approach enhances bioavailability and may amplify synergistic effects when combined with conventional chemotherapeutics or targeted agents.

Overall, the synergistic use of nanotechnological approaches and CBD-based therapies may open new avenues for research, offering the potential to significantly advance treatment efficacy in glioblastoma and other diseases.”

https://pubmed.ncbi.nlm.nih.gov/41288593

https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.5c00853


CBD Disrupts Malme-3M Cell Metabolism via Glycolytic Shift and Redox Imbalance

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“Background: Accumulating evidence suggests that cannabidiol (CBD) exerts variable effects on cancer cells that influence cellular activity, including growth. While anecdotal evidence abounds, mechanistic studies have lagged.

Methods: Malme-3M cells derived from melanoma and less-aggressive BJ fibroblast cells were incubated with CBD. CE-MS mass spectroscopy was used to measure metabolite changes resulting from CBD treatment.

Results: Data indicate a differential response between malignant Malme-3M cells and BJ fibroblasts with respect to metabolites critical for primary metabolic function. A significant reduction in TCA metabolites is seen with a corresponding increase in glycolytic output in the Malme-3M cell line. A similar reduction in TCA activity in BJ fibroblasts appears to differentially activate fatty acid oxidation. ATP is significantly reduced in the Malme-3M cells with a corresponding decrease in metabolites associated with redox maintenance.

Conclusions: This is the first metabolomics analyses of malignant Malme-3M cells and less-aggressive BJ fibroblasts after pre-treatment with CBD. The data suggest that the CBD-induced metabolic perturbation could reprogram cellular metabolism and affect ATP production and redox maintenance of the more-aggressive Malme-3M cells.”

https://pubmed.ncbi.nlm.nih.gov/41296432

“For the first time, an analysis of metabolomics of both less-aggressive BJ fibroblasts and malignant Malme-3M cells after pre-treatment with CBD has been made. As a result of CBD treatment, there is reprogramming of key metabolic processes including the TCA cycle, redox maintenance, and fatty acid oxidation. While more studies are needed to fully elucidate the mechanistic effects of CBD treatment, there is a clear and differential cellular metabolic consequence of CBD treatment between these cell types.”

https://www.mdpi.com/1467-3045/47/11/928

“This title means that the compound cannabidiol (CBD) disrupts the metabolism of Malme-3M cancer cells by forcing them to switch from their normal energy-producing processes to a more primitive, less efficient one called glycolysis, and by throwing off their cellular “redox” balance (a state of chemical reactions that are key to maintaining cell health). This metabolic disruption is a mechanism through which CBD may have anti-cancer effects.”

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

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“Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects.

Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality.

Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC.

This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.”

https://pubmed.ncbi.nlm.nih.gov/36696005/

https://link.springer.com/article/10.1007/s10555-023-10078-2

Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

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“Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect-the synergistic or antagonistic effect of various cannabinoids and terpenes.

In this work, we analyzed 25 cannabis extracts containing high levels of delta-9-tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells.

Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts. The efficiency of the extracts was tested by analyzing the expression of COX2 and IL6; while some extracts aggravated inflammation by increasing the expression of COX2/IL6 by 2-fold, other extracts decreased inflammation, reducing expression of cytokines by over 5-fold.

We next analyzed the level of THC, CBD, CBG and CBN and twenty major terpenes and performed clustering and association analysis between the chemical composition of the extracts and their efficiency in inhibiting cancer growth and curbing inflammation.

A positive correlation was found between the presence of terpinene (pval = 0.002) and anti-cancer property; eucalyptol came second, with pval of 0.094. p-cymene and β-myrcene positively correlated with the inhibition of IL6 expression, while camphor correlated negatively. No significant correlation was found for COX2. We then performed a correlation analysis between cannabinoids and terpenes and found a positive correlation for the following pairs: α-pinene vs. CBD, p-cymene vs. CBGA, terpenolene vs. CBGA and isopulegol vs. CBGA.

Our work, thus, showed that most of high-THC extracts demonstrate anti-cancer activity, while only certain selected extracts showed anti-inflammatory activity. Presence of certain terpenes, such as terpinene, eucalyptol, cymene, myrcene and camphor, appear to have modulating effects on the activity of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36144796

“Cannabis sativa is a plant with a long history of consumption as food and medicine. Delta-9-tetrahydrocannabinol (THC) is one of the main cannabinoids in cannabis; it has many properties, including anti-cancer, anti-inflammatory, analgetic and others.”

https://www.mdpi.com/1420-3049/27/18/6057/htm

The association between marijuana use and oral cancer risk: a systematic review and meta-analysis of case-control studies

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“The relationship between marijuana use and oral cancer risk remains controversial, with conflicting evidence from epidemiological studies. This systematic review and meta-analysis aimed to synthesize available evidence on the association between marijuana consumption and oral cancer incidence.

Following PRISMA guidelines, we conducted comprehensive searches across Scopus, PubMed, Web of Science, and Embase databases up to August 2025. We included only case-control studies reporting quantitative risk estimates for marijuana use and histologically confirmed oral cancer (ICD-10 codes C00-C06). Data extraction followed standardized protocols, and study quality was assessed using the Joanna Briggs Institute checklist. Statistical analyses were performed using Comprehensive Meta-Analysis software with random-effects models. Heterogeneity was evaluated using I2 statistics, and publication bias was assessed through funnel plots and Egger’s regression test. Six case-control studies involving 4,686 cases and 10,370 controls were included.

The pooled odds ratio demonstrated a statistically significant inverse association between marijuana use and oral cancer risk (OR = 0.659, 95% CI: 0.500-0.869, p = 0.003, I2 = 47.35).

Subgroup analyses were performed based on the duration of use, gender, and age at initiation of marijuana use; however, no clear dose-response relationship was observed. Sensitivity analyses confirmed robustness of findings, with ORs ranging from 0.599 to 0.708 across iterations. No significant publication bias was detected (Egger’s test p = 0.532). Three individual studies showed statistically significant protective effects, while three others were non-significant.

This meta-analysis suggests marijuana use is associated with reduced oral cancer risk.

However, given methodological limitations, heterogeneity in exposure assessment, and conflicting recent evidence, these findings require cautious interpretation. Future large-scale prospective cohort studies with standardized exposure measurements are essential for definitive conclusions.”


https://pubmed.ncbi.nlm.nih.gov/41236922/

https://www.tandfonline.com/doi/full/10.1080/15332640.2025.2581692

Durable complete response of advanced hepatocellular carcinoma using cannabis oil: a report of two cases

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“Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with a grim prognosis. Current treatment options for advanced HCC are limited, and a large proportion of patients is not amenable to any form of treatment, with best supportive care as the only remaining option.

Meanwhile, the use of cannabis-derived products is rising in oncological patients who are seeking symptom relief. Cannabinoids, similar to endogenous endocannabinoids, have shown promise in recent preclinical cancer research due to their ability to interact with various signaling pathways and molecular mechanisms of interest.

Case presentation

In this report, we present two patients (A aged 82 and B 77, respectively) with advanced HCC with a high tumor burden who demonstrated durable and complete regression after use of cannabis oil (A 10% delta-9-tetrahydrocannabinol (THC) and 5% cannabidiol (CBD), two droplets sublingually three times daily and B 15% THC and 2% CBD, 5 droplets sublingually two times daily) for symptom relief. The observations in this report build on previous (pre)clinical research highlighting the potential anti-tumor qualities of cannabinoids and stress the need for clinical trials investigating the anti-tumor effects of cannabinoids in cancer patients.

Conclusion

Based on the two cases presented here, we call for further research into the potential beneficial effect of cannabinoids in patients with advanced HCC.”

“The authors present two cases of durable and complete remission in two patients with advanced hepatocellular carcinoma using cannabinoids, thus stressing the call for further research into the anti-tumor effects of cannabinoids in this patient population with limited therapeutic options. These findings are hypothesis-generating and underscore the urgent need for controlled clinical trials.”

https://link.springer.com/article/10.1186/s42238-025-00353-0

https://pubmed.ncbi.nlm.nih.gov/41287047

Cannabidiol in pancreatic ductal adenocarcinoma: preclinical evidence, molecular mechanisms, and translational challenges

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“Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest and most treatment-resistant cancers, with limited progress in improving patient survival. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, has emerged as a potential anticancer agent due to its diverse molecular effects in preclinical cancer models.

Objective

This systematic review aims to evaluate the preclinical and early clinical evidence regarding CBD’s anticancer effects in PDAC, with emphasis on its molecular mechanisms, therapeutic synergies, and translational feasibility.

Methods

We systematically searched PubMed, Scopus, Web of Science, EMBASE, and Google Scholar (2006–2025) for studies examining the effects of CBD on PDAC in vitro, in vivo, and in clinical contexts. Studies were assessed for methodological quality and relevance to CBD-related antitumor activity.

Results

Fifteen studies met the inclusion criteria, including in vitro, animal, and limited clinical investigations. CBD exhibited antitumor properties via multiple pathways, such as CerS1-mediated ER stress and apoptosis, GPR55/MAPK inhibition, immune modulation, and chemosensitization to gemcitabine. Combination therapies (CBD with cannabinoids or chemotherapeutics) enhanced therapeutic outcomes in preclinical models. However, clinical evidence remains preliminary and insufficient to establish efficacy.

Conclusion

CBD demonstrates promising anticancer potential in PDAC through diverse molecular mechanisms and synergistic effects with chemotherapy. Nonetheless, significant translational barriers—including formulation variability, pharmacokinetics, and a lack of clinical trials—must be addressed. Further studies are warranted to validate these findings in human settings.”

https://pubmed.ncbi.nlm.nih.gov/41257868

“This systematic review provides a comprehensive synthesis of current evidence supporting cannabidiol (CBD) as a multifactorial anticancer agent in pancreatic ductal adenocarcinoma (PDAC).”

https://cancerci.biomedcentral.com/articles/10.1186/s12935-025-04062-9

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