Category Archives: Cancer

A comparative network analysis to explore cancer patient experiences with cannabis

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This study examined how people with cancer described the benefits and barriers they encountered when using CBD-only products compared with products containing both CBD and THC.

The findings point to a meaningful difference in patient experience: pain relief was especially prominent among those using CBD+THC products, while participants across the study also reported benefits including improved sleep, physical relaxation, emotional regulation, and reduced use of other medications.

“Introduction: Approximately 20% of cancer patients report cannabis use, yet only 30% of oncologists feel sufficiently informed to make recommendations on its use. This study aimed to visualize the network of themes that arise within cancer patients’ reported experiences with cannabis.

Materials and methods: Data was collected via an online survey of 65 patients who self-reported the use of cannabis in their treatment for cancer, details about the cannabis product(s) being used, their perceived benefits and problems associated with cannabis use, their reasons for starting cannabis use, and any reasons for stopping cannabis use. Epistemic Network Analysis (ENA) was used to compare two groups of cancer patients: 1) those who only used CBD-dominant products (CBD-only group) versus 2) those who used cannabidiol (CBD)- and delta-9-tetrahydrocannabinol (THC)-containing products (either CBD-dominant and THC-dominant cannabis products or cannabis products containing a balanced ratio of both CBD and THC; CBD+THC group).

Results: Cannabis use conferred therapeutic benefits for several health issues commonly encountered by cancer patients. Common benefits reported across the cohort of patients included pain relief, improved sleep, physical relaxation, emotional regulation, and reduction of concomitant medication. The most frequently reported barriers to cannabis use were the stigma associated with THC use and the high cost of CBD-dominant and THC-dominant products. Pain relief emerged as the most prominent, interconnected theme reported by the CBD+THC group, whereas emotional regulation was the most prominent theme for the CBD-only group.

Conclusion: Symptom relief differed based on the cannabinoid composition of the cannabis products. The following trends emerged, which must be confirmed with larger samples: pain relief was more prominent in responses from users of CBD+THC, whereas emotional regulation was more prominent in only the users of CBD-only products. These findings are a step toward assisting cancer patients and providers with clinical decision-making on cannabis use. This study highlights the continued perception of stigma associated with THC use and the need for insurance coverage of medicinal cannabis to reduce the financial burden for this patient population. Finally, this study exemplifies the value of ENA in studying the therapeutic utility of cannabis with qualitative data.”

https://pubmed.ncbi.nlm.nih.gov/42666469

“Pain relief is more frequently reported among users of CBD+THC products.”

“Emotional regulation is more frequently reported among users of only CBD.”

“Overall, pain relief was the most frequently discussed benefit and was associated with other benefits: emotional regulation, sleep or physical relaxation, and medication reduction. Primary patient concerns were stigma and cost.”

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2026.1737119/full

Cannabidiol Suppresses Glioma Growth and Limits Invasion Partly Through an LOXL2-Associated EMT-Like Program

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A new study found that cannabidiol (CBD) suppressed glioma growth and reduced tumor-cell migration and invasion in laboratory and animal models. The researchers linked part of this effect to reduced LOXL2 activity, suggesting CBD may interfere with molecular programs that help glioma cells spread into surrounding brain tissue.

The study adds new mechanistic evidence to the growing body of research examining CBD as a potential therapeutic compound in glioma and glioblastoma.

“Background: Gliomas, particularly glioblastoma, remain difficult to control because diffuse infiltration into surrounding brain tissue limits complete resection and contributes to recurrence. Cannabidiol (CBD), a nonpsychoactive cannabinoid capable of entering the central nervous system, has shown antitumor activity in glioma models, but the mechanisms underlying its anti-invasive effects remain unclear. Lysyl oxidase-like 2 (LOXL2) regulates extracellular-matrix remodeling and mesenchymal phenotypes in several cancers. We therefore tested the hypothesis that CBD limits glioma growth and invasion partly by suppressing an LOXL2-associated extracellular-matrix and EMT-like program.

Methods: Human U87 and murine GL261 glioma cells were used to examine CBD effects on tetrazolium-based cell viability, clonogenic growth, cell-cycle progression, apoptosis, migration, and invasion. The two cell lines provided complementary human and murine models, and the immunocompetent intracranial GL261 model enabled syngeneic in vivo validation. RNA sequencing and public glioma datasets were used to identify and contextualize CBD-responsive molecules. Mechanistic involvement was tested by determining whether LOXL2 knockdown phenocopied and LOXL2 overexpression attenuated the anti-invasive effects of CBD.

Results: CBD reduced glioma-cell viability and clonogenicity, induced G1-phase arrest and apoptosis, and suppressed migration and invasion. C CCK-8-derived IC50 values (mean ± SD, n = 3) at 24, 48, and 72 h were 36.5 ± 0.3, 26.7 ± 0.3, and 21.4 ± 0.3 μM in U87 cells and 33.3 ± 0.2, 29.3 ± 0.2, and 25.5 ± 0.4 μM in GL261 cells, respectively. CBD treatment was accompanied by reduced MMP2 and MMP9 expression and increased TIMP3 expression. Transcriptomic profiling identified LOXL2 as a prominent CBD-downregulated molecule, and public datasets associated higher LOXL2 expression with aggressive molecular features and shorter overall survival. LOXL2 silencing reproduced the antimigratory and anti-invasive phenotype, whereas LOXL2 overexpression enhanced cell motility and partially attenuated the effects of CBD. The partial rescue involved vimentin, MMP9/TIMP3, EMT-related transcription factors, and F-actin-rich protrusions. In vivo, CBD reduced intracranial tumor burden and produced tissue changes consistent with lower proliferation, enhanced apoptosis, and suppression of the LOXL2-associated mesenchymal program.

Conclusions: CBD suppresses glioma growth and limits invasion, at least in part, by attenuating an LOXL2-associated EMT-like and extracellular-matrix-remodeling program. Because LOXL2 overexpression produced only a partial rescue and direct target engagement was not tested, LOXL2 should be interpreted as a functional mediator rather than the sole or direct molecular target of CBD. These findings support further validation in patient-derived and pharmacokinetically informed glioma models.”

https://pubmed.ncbi.nlm.nih.gov/42661582

https://onlinelibrary.wiley.com/doi/10.1155/bmri/6385332

Lower Rates of Hepatocellular Carcinoma Observed Among Cannabis Users: A Population-Based Study

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Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains a major cause of cancer death worldwide.

In a population-based study involving more than 101 million U.S. hospital patients, researchers found a striking association between cannabis use and HCC: after adjusting for multiple potential confounding factors, patients with documented cannabis use were 55% less likely to have hepatocellular carcinoma than patients without documented cannabis use.

The study adds large-scale human observational evidence to earlier preclinical research examining cannabinoids and liver cancer.

“Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the fourth leading cause of cancer deaths in the world. The association between HCC and cannabis has been identified in mice; however, to our knowledge has not been identified in humans. Therefore, we aim to investigate the relation between HCC and cannabis use in humans.

Methods: Using data from the National Inpatient Sample (NIS) database between 2002 and 2014, we identified the patients with HCC and cannabis use diagnosis using the International Classification of Disease 9th version codes (ICD-9). Then, we identified patients without cannabis use as the control group. We adjusted for multiple potential confounders and performed multivariable logistic regression analysis to determine the association between cannabis abuse and HCC.

Results: A total of 101,231,036 patients were included in the study. Out of the total, 996,290 patients (1%) had the diagnosis of cannabis abuse versus 100,234,746 patients (99%) in the control group without cannabis abuse. We noticed that patients with cannabis abuse were younger (34 vs 48 years), had more males (61.7% vs 41.4%) and more African Americans (29.9% vs 14.2%) compared with the control group (P<0.001 for all). Besides, patients with cannabis use had more hepatitis B, hepatitis C, liver cirrhosis, and smoking, but had less obesity and gallstones, (P<0.001 for all). Using multivariable logistic regression, and after adjusting for potential confounders, patients with cannabis abuse were 55% less likely to have HCC (adjusted Odds Ratio {aOR}, 0.45, 95% Confidence Interval {CI}, 0.42-0.49, P<0.001) compared with patients without cannabis abuse.

Conclusion: Based on our large database analysis, we found that cannabis use patients were 55% less likely to have HCC compared to patients without cannabis use. Further prospective studies are needed to assess the role of cannabis use on HCC.”

https://pubmed.ncbi.nlm.nih.gov/35651376

“Our analysis revealed that cannabis users were 55% less likely to have HCC compared to non-cannabis users.” 

https://www.cureus.com/articles/90568-lower-rates-of-hepatocellular-carcinoma-observed-among-cannabis-users-a-population-based-study#!

Phase I/II Double-Blind, Randomized Controlled Trial of Medicinal Cannabis on Quality of Life and Symptoms in Advanced Cancer: RESONANCE Trial Protocol

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This study represents an important part of Olivia Newton-John’s legacy.

After experiencing medicinal cannabis personally during her long cancer journey, Olivia became an outspoken advocate not only for patient access, but for the scientific research needed to determine what cannabis could—and could not—do for people living with cancer.

The Olivia Newton-John Cancer Research Institute later stated that Olivia’s own experience with medicinal cannabis and her interest in pursuing the science behind its use in cancer helped lead the Institute to undertake its first medicinal-cannabis clinical trial.

That work developed into the RESONANCE trial, a Phase I/II double-blind, randomized controlled study examining medicinal cannabis in people with advanced cancer. The study is investigating its effects on quality of life and symptoms including pain, nausea, appetite loss, anxiety and sleep problems, as well as safety and how cannabinoids are metabolized by the body. The study protocol was published in Clinical Therapeutics in 2026.

Olivia repeatedly made clear that her personal experience was not enough. She wanted the science. She wanted researchers to investigate the benefits she believed she had experienced and determine whether other cancer patients could benefit as well.

The study is currently recruiting

As of August 2026, the RESONANCE trial is listed as open and recruiting in Victoria, Australia.

Potential participants may be eligible if they:

  • are 18 years of age or older;
  • have advanced cancer; and
  • have an estimated life expectancy of at least two months.

Additional inclusion and exclusion requirements apply, and final eligibility must be determined by the study team.

Two-thirds of participants receive medicinal cannabis and one-third receive placebo. Both are administered as an oral oil, beginning once daily and increasing, when appropriate, to a maximum of three times per day. Dosing is increased until symptoms are adequately controlled and is then maintained for up to one month. Participants provide blood samples and complete questionnaires, and researchers may also invite a participant’s caregiver to take part in aspects of the study.

After completion of the trial period, participants may be able to obtain medicinal cannabis through compassionate access.

Clinical trial registration: ACTRN12619001534178.

Interested in participating?

People interested in the trial should discuss participation with their doctor and contact the research center to determine whether they meet the complete eligibility requirements. Peter MacCallum Cancer Centre currently lists the study as open and recruiting and directs prospective participants to the full Australian clinical-trial registry criteria.

Dr. Jodie Palmer
Olivia Newton-John Cancer Research Institute
Level 5, ONJWRC
145 Studley Road
Heidelberg, Victoria 3084, Australia
Phone: +61 3 9496 3573
Email: trials@onjcri.org.au

Olivia spent the final years of her life asking that medicinal cannabis be taken seriously enough to study scientifically. She believed her own experience raised questions worth answering.

This study is part of the scientific legacy she helped set in motion.

“Purpose: Medicinal cannabis is increasingly used in cancer care despite limited high-quality evidence to inform practice. It is increasingly legalized around the world; however, this has outpaced high-quality research on cancer symptom outcomes, leading to patient and prescriber uncertainty. This trial evaluates the safety profile, tolerability, and impact of medicinal cannabis on quality of life in advanced cancer.

Methods: This is a Phase I/II multicenter clinical trial. The Phase I component is open-label and aims to determine the safety profile and tolerability of medicinal cannabis use by evaluating clinical outcomes and pharmacokinetic profile. The Phase II component is a double-blind, randomized clinical trial that aims to determine the impact of medicinal cannabis on quality of life and symptom control (pain, anorexia, anxiety, sleep, nausea, treatment satisfaction, toxicity, and caregiver burden) using validated instruments in people with advanced cancer.

Findings & implications: This trial is expected to generate important knowledge about the tolerability, efficacy, and adverse effects of medicinal cannabis in people with advanced cancer, with a particular focus on quality of life and symptom burden. Protocol adaptations aimed at enhancing inclusivity may be worth noting in future studies. Collectively, the findings have the potential to inform clinical practice, reduce decisional uncertainty among prescribers and patients, and affect care for the estimated 10 million people who die of advanced cancer annually worldwide. Australian New Zealand Clinical Trials Registry identifier: ACTRN12619001534178.”

https://pubmed.ncbi.nlm.nih.gov/42476829

https://www.clinicaltherapeutics.com/article/S0149-2918(26)00233-X/fulltext

Synergistic In Vitro Effects of Minor Phytocannabinoids and Melatonin Combinations Against Human Glioblastoma Cells

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“The prognosis of glioblastoma (GBM) patients remains dismal due to chemoresistance.

Repurposing of natural and endogenous compounds, such as the pineal hormone melatonin (MLT) and minor phytocannabinoids like cannabinol (CBN) or cannabigerol (CBG), represents a promising strategy.

This study investigates the cytotoxic potential of combining these phytocannabinoids with MLT, evaluating their efficacy both alone and synergistically with temozolomide (TMZ) to overcome drug resistance.

To achieve this, cytotoxicity, synergy (Bliss model), and selectivity were evaluated in U87, T98, and U251 GBM lines and normal astrocytes. Mechanisms of damage were characterized via Western blot (γH2AX and PARP-1), flow cytometry using fluorescent dyes/probes (DCFDA, JC-1, MitoBright, BODIPY, PI, and Annexin-V), or the protein marker COX IV and confocal analysis.

The results demonstrated that CBN-MLT and CBG-MLT regimens exerted synergistic cytotoxicity while sparing healthy astrocytes. Notably, combining these regimens (U87: MLT 0.3 mg/mL + CBN 25 µM; MLT 0.2 mg/mL + CBG 15 µM. T98: MLT 0.7 mg/mL + CBN 25 µM; MLT 0.6 mg/mL + CBG 30 µM. U251: MLT 0.4 mg/mL + CBN 20 µM; MLT 0.5 mg/mL + CBG 35 µM) with TMZ significantly enhanced chemotherapeutic efficacy, overcoming baseline effects of TMZ in these cell lines.

The combinations induced necrotic cell death characterized by severe double-strand DNA damage. This was driven by an early accumulation of intracellular ROS, which triggered mitochondrial depolarization, loss of organelle mass, and lipid peroxidation. CBN combinations consistently triggered more robust biochemical alterations than CBG-based treatments.

Taken together, this study provides a strong preclinical basis for utilizing minor cannabinoids combined with MLT in GBM management.

Crucially, this co-treatment emerges as a promising approach to potentiate TMZ efficacy, offering a novel and potentially effective therapeutic strategy to counter GBM resilience.”

https://pubmed.ncbi.nlm.nih.gov/42589431

“In recent years, the repurposing of endogenous compounds and natural products has emerged as a promising frontier in neuro-oncology. Among these, the pineal hormone melatonin (MLT) and phytocannabinoids derived from Cannabis sativa, most notably Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have shown strong individual anti-cancer effects “

“Crucially, phytocannabinoids are capable of inhibiting tumor growth, inducing cancer cell death, and modulating the immune microenvironment. Moreover, they have demonstrated a distinct ability to enhance the effectiveness of conventional therapies and sensitize chemotherapeutic treatments, helping to overcome established resistance mechanisms.”

https://www.mdpi.com/1422-0067/27/15/6774


Cannabidiol- and Celecoxib-Loaded Liposomes as a Strategy to Modulate Redox and Inflammatory Signaling in High-Grade Glioma: A Preliminary In Vivo Study

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“Inflammation contributes to the rapid progression of high-grade gliomas, indicating that anti-inflammatory strategies targeting NF-κB signaling may offer therapeutic benefit.

Cannabidiol (CBD) and celecoxib (CELE) are hydrophobic pharmacological agents whose formulation in lipid carriers may support their combined biological evaluation.

In this proof-of-concept study, we investigated liposomal formulations containing CBD, CELE, or both compounds in U-87 MG high-grade glioma cells and in a subcutaneous xenograft model.

We assessed cytotoxicity, apoptosis, oxidative stress, Nrf2-dependent responses, NF-κB-centered inflammatory networks, tumor cell invasive properties, and Wnt/β-catenin pathway activity. The nanoformulations induced reactive oxygen species generation by 1.8-fold, which was accompanied by Nrf2 activation. Cationic formulations loaded with the compounds produced more pronounced pro-apoptotic effects (up to 39%) than POPC liposomes, although both types reduced the nuclear translocation of the NF-κB p65 subunit.

The CBD + CELE-containing formulation showed a trend toward reduced tumor progression in mice. It is important to note that the in vitro and in vivo nanoformulations were physicochemically related, but not identical, and the in vivo experiment should be interpreted as a preliminary assessment after intratumoral administration.

Overall, cationic liposomes co-loaded with CBD + CELE represent a promising platform for further optimization aimed at coordinated modulation of inflammatory, oxidative, and proliferative pathways in glioma. However, additional studies, including tissue distribution, release kinetics, and efficacy in orthotopic glioma models, are needed to fully verify their translational potential.”

https://pubmed.ncbi.nlm.nih.gov/42511566

“In summary, this study shows that liposomal formulations containing CBD and CELE, particularly DOTAP:POPC formulations prepared with both compounds, modulate apoptosis, cell cycle distribution, oxidative stress, Nrf2/NF-κB/Wnt-related pathways, and glioma-associated inflammatory mediators in U-87 MG-based models. In the subcutaneous xenograft model, intratumoral administration of the CBD + CELE-containing formulation was associated with a trend toward reduced tumor progression and modulation of selected tumor-associated proteins.”

https://www.mdpi.com/1422-0067/27/14/6220

A Comparative Analysis of the Action Mechanisms of Cannabidiol, Cannabigerol, and Cannabinol in Human Cholangiocarcinoma Cell Lines

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“Background: Chemoresistance remains a major obstacle in managing cholangiocarcinoma (CCA). The cannabis plant contains several phytocannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), which exhibit anticancer properties. However, to the best of our knowledge, their effects on CCA have not been previously investigated. This study aimed to explore the molecular mechanisms underlying the anticancer effects of CBD, CBG, and CBN in CCA cells. 

Methods: KKU-100 and KKU-452 cells were treated with varying concentrations of CBD, CBG, and CBN for 24 and 48 h. Cytotoxicity was assessed using the MTT assay, and half maximal inhibitory concentration (IC50) values were calculated. KKU 452 cells were further analyzed for apoptosis, mitochondrial membrane potential (MMP), and Ki67 expression using flow cytometry. Proteomics profiling was performed to compare the effect of these cannabinoids with those of gefitinib and cisplatin. 

Results: Monotherapy with CBD, CBG, or CBN induced dose-dependent cytotoxicity at 24 and 48 h with lower IC50 values than those of cisplatin and comparable efficacy to that of gefitinib. At low doses, CBD, CBG, and CBN induced early apoptosis, while higher doses triggered late apoptosis. MMP loss increased by 2.5-, 4.9-, and 1.7-fold, respectively, after 6 h. Ki67, highly expressed in KKU-452 cells (Ki67-positive ratio = 3.16 ± 0.16), was significantly reduced after the cannabinoid treatment, with Ki67-positive ratios of 0.38 ± 0.22, 0.38 ± 0.13, and 0.32 ± 0.23 for CBD, CBG, and CBN, respectively. Proteomics analysis identified 2781 proteins affected by CBD, CBG, CBN, cisplatin, and gefitinib. All three cannabinoids downregulated key upstream regulatory proteins (LARP1, TFEB, and BCR). Similar patterns of LARP1 and TFEB downregulation were also observed with cisplatin and gefitinib. CBN showed the closest similarity to cisplatin, followed by gefitinib, by targeting CDK4/6 and PCGEM1 proteins. CBD and CBG exhibited the greatest similarity to each other, also influencing MASTL expression. 

Conclusions: CBD, CBG, and CBN exhibit potential anticancer activity in CCA by suppressing proliferation, reducing Ki67 expression, and inducing apoptosis through MMP disruption. The identification of shared molecular targets, including LARP1 and TFEB, provides new mechanistic insight and supports the potential development of cannabinoid-based therapeutic strategies for cholangiocarcinoma.”

https://pubmed.ncbi.nlm.nih.gov/42513130

“CBD, CBG, and CBN exhibited significant anti-cholangiocarcinoma activity by reducing cell viability, suppressing proliferation, decreasing nuclear Ki67 expression, disrupting mitochondrial membrane potential, and inducing apoptosis in KKU-452 cells.”

https://www.mdpi.com/1420-3049/31/14/2446


Preclinical antitumor evaluation of a tetrahydrocannabinol and cannabidiol (1:6) cannabis extract in an MCF-7 xenograft model of estrogen receptor-positive breast cancer

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“Background and aim: Breast cancer remains one of the leading causes of cancer-related mortality worldwide, despite advances in surgery, chemotherapy, endocrine therapy, and targeted treatments. Cannabinoids derived from Cannabis sativa, particularly tetrahydrocannabinol (THC) and cannabidiol (CBD), have demonstrated anticancer properties in several experimental models; however, in vivo evidence in estrogen receptor (ER)-positive breast cancer remains limited. This study aimed to evaluate the antitumor effects of a THC:CBD (1:6) cannabis extract in a Michigan Cancer Foundation-7 breast cancer cell line (MCF-7) xenograft mouse model of ER-positive breast cancer.

Materials and methods: Female BALB/c nude mice bearing MCF-7 xenograft tumors were randomly assigned into five groups (n = 5/group): negative control (sesame oil), positive control treated with 5-fluorouracil (5-FU; 20 mg/kg), and three treatment groups receiving oral THC:CBD (1:6) extract at doses of 2, 10, or 20 mg/kg body weight for 30 consecutive days. Tumor growth was monitored throughout the experiment. Histopathological examination and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) expression were performed to evaluate apoptosis-related morphology and tumor cell proliferation. Hematological and biochemical parameters were assessed to determine systemic safety.

Results: Cannabinoid-treated groups exhibited significant suppression of tumor growth compared with the negative control group. Tumor volume reduction was observed in all treatment groups, with the greatest reduction detected in the high-dose THC:CBD group. Histopathological evaluation revealed increased numbers of tumor cells exhibiting morphological features consistent with apoptosis in cannabinoid-treated mice. Immunohistochemical analysis demonstrated significantly lower PCNA expression scores in all THC:CBD-treated groups compared with both negative and positive controls, indicating reduced tumor cell proliferation. Hematological parameters remained within normal physiological ranges in cannabinoid-treated animals. However, elevated alanine aminotransferase and aspartate aminotransferase levels were observed in the high-dose group, suggesting potential dose-related hepatic stress.

Conclusion: The THC:CBD (1:6) cannabis extract demonstrated significant antitumor activity in an MCF-7 xenograft model by suppressing tumor progression primarily through inhibition of tumor cell proliferation, with supportive apoptosis-related histological features. These findings provide novel in vivo evidence supporting the potential of cannabinoid-based formulations as adjunctive therapeutic approaches for ER-positive breast cancer.”

https://pubmed.ncbi.nlm.nih.gov/42494695

“In conclusion, the present study demonstrated that the THC:CBD (1:6) whole-cannabis extract exerted significant antitumor activity in an MCF-7 xenograft model of ER-positive breast cancer. Treatment with the cannabinoid extract resulted in marked suppression of tumor growth, significant reduction in tumor volume, decreased PCNA expression, and increased numbers of tumor cells exhibiting apoptosis-related morphological features.

Among the tested doses, the high-dose THC:CBD group showed the greatest reduction in tumor volume, indicating a strong antiproliferative effect of the cannabinoid formulation.”

“Overall, despite the inherent limitations of xenograft models, the present findings indicate that the THC:CBD (1:6) cannabis extract possesses promising antiproliferative and antitumor properties in ER-positive breast cancer. These results provide a foundation for future mechanistic and translational studies exploring cannabinoids as potential adjunctive agents in breast cancer therapy.”

https://veterinaryworld.org/Vol.19/June-2026/17.php

Cannabis sativa phytochemicals in cancer therapy: molecular mechanisms and therapeutic potential

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“Background: The therapeutic potential of Cannabis sativa has attracted growing interest in oncology. Its diverse phytochemicals, including cannabinoids, flavonoids, and terpenes, interact with oncogenic signaling pathways and the endocannabinoid system influencing tumour progression and therapeutic responses.

Objective: This review critically evaluates the molecular mechanisms by which Cannabis sativa phytochemicals modulate cancer pathways, with emphasis on apoptosis, oxidative stress regulation, autophagy, angiogenesis, and metastasis. It also explores synergistic and additive interactions among cannabinoids and flavonoids, highlighting their translational relevance.

Key findings: Cannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG) exhibit pathway-specific effects, including induction of apoptosis, modulation of oxidative stress, and inhibition of angiogenesis. Flavonoids such as cannflavin A, genistein, daidzein, hesperetin, and naringenin exhibit selective cytotoxicity across bladder, breast, melanoma, and pancreatic cancers, often sparing normal tissue. Importantly, phytochemical interactions are not uniformly synergistic; while combinations such as THC and CBD amplify apoptotic signaling, others act additively or antagonistically. Clinical formulations such as Nabiximols provide translational evidence of cannabinoid synergy, although outcomes remain context-dependent.

Conclusion: The disconnect between preclinical efficacy and clinical outcomes underscores critical gaps in dosing strategies, patient selection, and combination regimens. Future research should prioritize mechanistic studies, rational phytochemical combinations, and innovative drug delivery systems. Taken together, Cannabis sativa phytochemicals emerge as promising molecular entities with the potential to reshape integrative oncology, provided their therapeutic promise is matched with rigorous, evidence-based evaluation.”

https://pubmed.ncbi.nlm.nih.gov/42416829

“Taken together, these findings position Cannabis sativa phytochemicals not merely as natural products of interest, but as promising molecular entities with the potential to reshape integrative oncology.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1768210/full

Cannabidiol Activates Integrated Stress Response Signaling and Immune Trafficking Programs in an A375 Melanoma-Jurkat T Cell Coculture Model: A Multi-Omics Analysis

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“Cannabidiol (CBD) is a nonpsychoactive cannabinoid with emerging anticancer and immunomodulatory properties; however, its systems-level mechanisms in tumor-associated immune cells remain incompletely defined.

Here, we investigated CBD in a melanoma-T cell coculture model using integrated transcriptomic and proteomic analyses.

At a subcytotoxic concentration (10 μM), CBD selectively induced apoptosis in melanoma while preserving T-cell viability and enhancing IL-2 secretion. RNA sequencing revealed coordinated activation of stress-adaptive, immune activation, and trafficking programs, including modulation of T-cell receptor signaling and cytokine networks.

Data-independent acquisition proteomics identified activation of eukaryotic initiation factor 2 (EIF2) signaling, a central node of the integrated stress response (ISR) linking redox and endoplasmic reticulum stress to translational control. Multiomics integration converged on immune cell trafficking as a consistent outcome, with upregulation of ICAM1, ITGB1, and associated adhesion-related proteins.

These findings suggest ISR-dependent translational reprogramming as a putative mechanistic axis by which CBD reshapes T-cell function in the melanoma microenvironment.

Our study provides pharmacological insight into how CBD modulates tumor-immune interactions and suggests potential utility as an adjunct immunomodulatory agent in melanoma.”

https://pubmed.ncbi.nlm.nih.gov/42396083

“Plant-derived redox-active metabolites have emerged as important modulators of these stress-adaptive pathways, acting through conserved molecular nodes that integrate oxidative stress with cellular signaling. Cannabidiol (CBD) is a nonpsychoactive phytochemical that has attracted growing attention as a redox-active compound with antioxidant, cytoprotective, and anticancer properties. Apart from its direct effects on tumor cells, CBD has been reported to modulate inflammatory signaling, oxidative stress responses, and cell death pathways, including ferroptosis.”

“In conclusion, this study provides a comprehensive multiomics characterization of CBD’s role in reshaping T-cell function within the melanoma microenvironment through redox- and stress-responsive mechanisms. Using a melanoma-T cell coculture system, we demonstrate that CBD selectively promotes melanoma cell death while inducing coordinated transcriptomic and proteomic remodeling in T cells.”

https://pubs.acs.org/doi/10.1021/acsomega.6c01965