Category Archives: Cancer

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 (MT1, MT2, and SLC30A2) and p53-mediated apoptosis (TP53TG3, DDIT4, BBC3, CHAC1, NOXA1, 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

Optimal Cannabinoid-Terpene Combination Ratios Suppress Mutagenicity of Gastric Reflux in Normal and Metaplastic Esophageal Cells

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“Background: Esophageal adenocarcinoma (EAC) frequently arises from chronic exposure to acid and bile reflux, with secondary bile acids, such as deoxycholic acid (DCA), contributing to its pathogenesis through mechanisms involving reactive oxygen species (ROS), oxidative DNA damage, and resistance to apoptosis. The human endocannabinoid system (ECS) regulates diverse anti-inflammatory, antioxidant, and analgesic pathways implicated in disease modulation. Despite its therapeutic promise, effective pharmacological activation of the ECS remains challenging.

Objectives: This study aimed to evaluate whether specific cannabinoid-terpene combinations targeting the ECS could attenuate the mutagenic and cytotoxic effects of bile acid-induced stress in esophageal cell models. Additionally, we assessed the clinical significance of ECS-related protein receptors in the progression of EAC.

Design: In vitro experimental models combined with clinical samples analyses.

Methods: We utilized in vitro models, including human esophageal epithelial cell lines exposed to DCA and a Barrett’s esophagus gastroesophageal reflux (GER) model subjected to low pH and a bile acid cocktail. Patient-derived samples were analyzed to investigate the clinical association of ECS pathway markers with EAC progression. Experimental models were treated with varying ratios of phyto-cannabinoids and terpenes. Endpoints included assessment of DNA damage, mitochondrial membrane potential, and ROS production to identify optimal compound combinations. Expression of ECS-related protein receptors was evaluated in clinical samples to elucidate their role in EAC development.

Results: A 1:5 ratio of cannabigerol (CBG) to Phytol (Phy) was found to significantly reduce DCA-induced DNA damage, preserve mitochondrial membrane potential, and decrease ROS levels. This combination also enhanced apoptosis in damaged cells and diminished mutagenicity. Analysis of patient samples revealed that the expression of the ECS-associated receptor protein CB1 correlated with EAC progression, suggesting a broader clinical role for ECS modulation in cancer prevention.

Conclusion: Modulation of the ECS through carefully selected cannabinoid-terpene ratios can mitigate bile acid-induced esophageal damage and may reduce carcinogenic progression. These findings support further in vivo investigations and raise the possibility of expanding cannabinoid-terpene therapeutics to other conditions involving similar pathogenic processes.”

https://pubmed.ncbi.nlm.nih.gov/41040236/

https://www.biorxiv.org/content/10.1101/2025.09.23.678062v1

Impact of Medical Cannabis on the Quality of Life of Cancer Patients: A Critical Review

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“Purpose: This study aimed to review the literature on the impact of medical cannabis (MC) on the quality of life (QoL) of cancer patients. 

Materials and Methods: A critical review was conducted using PubMed, Latin American and Caribbean Health Sciences Literature, Scopus, Virtual Health Library, and Embase. The inclusion criteria were access to the full content; in English, Spanish, or Portuguese; published until January 2025, relating “Cancer,” “Quality of Life,” and “Medical Cannabis.” Of the 267 articles identified, 16 were selected for the final analysis. 

Results: The studies suggest that MC can improve mental health, sleep, appetite, and pain in cancer patients and decrease nausea, vomiting, and the use of other medications, such as opioids. Increased survival time and cognitive function improvements were also observed, with mild or moderate adverse effects. Both tetrahydrocannabinol and cannabidiol (full spectrum) were commonly used, with varied intervention durations. 

Conclusion: Despite differences and methodological limitations, including only four randomized clinical trials, which precluded systematic review or meta-analysis, findings suggest that MC may improve QoL for cancer patients by alleviating physical and psychosocial symptoms associated with cancer treatment. In contrast, some mild or moderate adverse effects may be present. Moreover, the use of MC faces challenges such as the interaction with some chemotherapy treatment. More randomized controlled trials are needed to better understand the effects of MC among oncology patients.”

https://pubmed.ncbi.nlm.nih.gov/40932699/

https://www.liebertpub.com/doi/10.1177/27683605251377417

Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer

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Biochemical Pharmacology

“Breast cancer is the second leading cause of death among women. Although early diagnosis and development of new treatments have improved their prognosis, many patients present innate or acquired resistance to current therapies. New therapeutic approaches are therefore warranted for the management of this disease.

Extensive preclinical research has demonstrated that cannabinoids, the active ingredients of Cannabis sativa, trigger antitumor responses in different models of cancer.

Most of these studies have been conducted with pure compounds, mainly Δ9-tetrahydrocannabinol (THC). The cannabis plant, however, produces hundreds of other compounds with their own therapeutic potential and the capability to induce synergic responses when combined, the so-called “entourage effect”.

Here, we compared the antitumor efficacy of pure THC with that of a botanical drug preparation (BDP).

The BDP was more potent than pure THC in producing antitumor responses in cell culture and animal models of ER+/PR+, HER2+ and triple-negative breast cancer. This increased potency was not due to the presence of the 5 most abundant terpenes in the preparation. While pure THC acted by activating cannabinoid CB2 receptors and generating reactive oxygen species, the BDP modulated different targets and mechanisms of action. The combination of cannabinoids with estrogen receptor- or HER2-targeted therapies (tamoxifen and lapatinib, respectively) or with cisplatin, produced additive antiproliferative responses in cell cultures. Combinations of these treatments in vivo showed no interactions, either positive or negative.

Together, our results suggest that standardized cannabis drug preparations, rather than pure cannabinoids, could be considered as part of the therapeutic armamentarium to manage breast cancer.”

“It is well documented that cannabinoids, the active ingredients of the hemp plant Cannabis sativa, produce antitumor responses in preclinical models of cancer, by tackling different stages of cancer progression such as uncontrolled cancer cell proliferation and survival, angiogenesis and metastasis. The vast majority of these studies has been performed with pure compounds, mainly Δ9-tetrahydrocannabinol (THC). The cannabis plant, however, produces hundreds of additional compounds (other cannabinoids, terpenoids, flavonoids, polyphenols, etc.) that have been much less studied but show promising therapeutic properties (anti-proliferative, anti-inflammatory, immune-stimulant, etc.), and/or the potential capability of enhancing some THC actions, the so-called “entourage effect”.

https://www.sciencedirect.com/science/article/abs/pii/S0006295218302387

UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols

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Pharmacological Research - Natural Products

“Cannabis sativa is one of the most extensively researched plant species that holds promising therapeutic and ethnomedicinal significance.

Various parts of the species including fan leaves, flowers and trichomes are well documented for their richness in cannabidiol (CBD) and tetrahydrocannabidiol (THC) contents. However, an overlooked part of C. sativa, the sugar leaves, which are wasted during harvesting has plethora of CBD and THC and yet to investigated.

In this study we investigated the ethanol extract of sugar leaves of C. sativa (CSLE) for chemical composition through UHPLC-Q-TOF-MS analysis and pharmacological potential by using various in vitro antioxidant, antidiabetic, nitric oxide inhibition and anticancer studies. Furthermore, in silicomolecular docking analysis was performed for 10 selected compounds against α-glucosidase and α-amylase.

The UHPLC-Q-TOF-MS profiling of CSLE revealed the tentative identification of 37 compounds including CBD, THC, terpenes and flavonoids. The cytotoxicity studies presented highest activity against breast cancer cell lines (MDA-MB-231, IC50= 18.12 ± 1.13 µg/mL) followed by lung, liver and colorectal cancer cell lines.

Similarly, CSLE showed significant antidiabetic activity by inhibiting α-glucosidase (IC50= 3.13 ± 2.78 µg/mL) and α-amylase. The in vitro antioxidant assays gave highest activity in ABTS followed by DPPH method as well as potentially inhibited nitric oxide (NO) formation. The computational analysis revealed good docking interaction of CBD, THC, selected terpene and flavonoids against α-glucosidase and α-amylase.

Overall, the findings present the sugar leaves of C. sativa as the undisputed rich source of CBD, THC, terpenes and flavonoids with multifaceted therapeutic potential in diabetes, inflammation and different types of cancers. However, there is need of further investigations on toxicity profile and in-depth pharmacological evaluation through in vivo disease bearing animal models.”

https://www.sciencedirect.com/science/article/abs/pii/S2950199725001429

“The research titled “UHPLC-Q-TOF-MS profiling and multifaceted antioxidant, antihyperglycemic and anticancer potential of Cannabis sativa sugar leaves: An unexplored source of cannabidiol, terpenes and polyphenols” identifies sugar leaves of Cannabis sativa as a potential source for multiple therapeutic compounds, including cannabidiol, terpenes, and polyphenols. Through UHPLC-Q-TOF-MS analysis, the study found that these sugar leaf extracts exhibit antioxidant, antihyperglycemic (anti-diabetic), and anticancer activities against various cancer cell lines. The specific compounds present in the sugar leaves, when combined with other plant compounds like terpenes and flavonoids, demonstrate a phenomenon known as the entourage effect, which could enhance their therapeutic potential.”