Category Archives: Cancer

Cannabidiol-loaded-injectable depot formulation for the treatment of triple-negative breast cancer: design, development, in-vitro and in-ovo evaluation of its anticancer activity

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“Triple-negative breast cancer (TNBC) is an invasive and difficult-to-treat carcinoma that represents 15-20 % of breast malignancies and is frequently diagnosed in younger women. Chemotherapy is the mainstay treatment approach.

Cannabidiol (CBD), the main non-psychoactive cannabinoid, has shown a potential anticancer activity in TNBC, enhancing the effect of conventional antineoplastics.

This research aims to develop in situ forming implants (ISFIs) as a long-acting depot formulation of CBD with potential application in TNBC. This formulation is intended to be administered in the tumor site during neoadjuvant chemotherapeutic regimens, allowing a controlled CBD release. ISFIs were elaborated with 100 mg of polycaprolactone (PCL) and 2.5 mg (2.5-CB-ISFI), 5 mg (5-CB-ISFI) or 10 mg (10-CB-ISFI) of CBD dissolved in 400 µL of NMP. All the formulations exhibited a controlled drug release for around two months. 10-CB-ISFI formulation with the highest CBD content and the most suitable CBD release profile was selected for biological studies.

This formulation inhibited the proliferation and migration of MDA-MB-231 and 4T1 cells and exerted an antiangiogenic effect in ovo. Interestingly, the antiangiogenic activity of 10-CB-ISFI was higher compared with CBD in solution administered at the same concentration, showing vascular inhibition percentages of around 80 % and 60 %, respectively.

Finally, this formulation reduced the growth of MDA-MB-231-derived tumors developed in the chorioallantoic membrane (CAM) model. The single administration of 10-CB-ISFI exhibited a similar antitumor efficacy to the daily administration of CBD in solution (≈60 % tumor growth inhibition).

Therefore, the injectable depot formulation of CBD developed in this work showed a promising utility in TNBC treatment.”

https://pubmed.ncbi.nlm.nih.gov/40349999/

https://www.sciencedirect.com/science/article/pii/S0378517325005472?via%3Dihub

Cannabinol improves exemestane efficacy in estrogen receptor-positive breast cancer models: a comparative study with cannabidiol

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“Cannabinoids have been used as anti-emetic agents in cancer. However, multiple studies suggest that cannabinoids present important anti-tumor actions as well.

Estrogen receptor-positive (ER+) breast cancer is the most diagnosed breast cancer subtype, and despite the success of endocrine therapy, endocrine resistance development is a major challenge, demanding the discovery or implementation of alternative therapeutic approaches.

In line with this, and following our previous work, the benefits of combining the aromatase inhibitors (AIs) used in the clinic, anastrozole (Ana), letrozole (Let), and exemestane (Exe), with cannabinol (CBN) were evaluated. Experiments were performed in MCF-7aro cells and spheroids to assess activity against specific molecular targets and underlying mechanisms of action.

Among the three AIs studied, only the combination of CBN with Exe induced a significant beneficial impact on viability and growth of ER+ breast cancer cells and spheroids.

Our results demonstrated that this combination was more effective than Exe in preventing the expression of aromatase and in modulating ERα and androgen receptor (AR) activity.

In fact, the results revealed that CBN can prevent de novo synthesis of aromatase, surpass Exe’s weak estrogen-like effect, and avoid the unfavorable overexpression of AR. By comparing these two therapeutic strategies, as well as the previously studied combination of Exe plus cannabidiol (CBD), differential transcriptome profiles were detected, which may help to better understand the mechanism of action of cannabinoids and disclose their full potential in breast cancer treatment.

In conclusion, this study strengthens the hypothesis that cannabinoids are important anti-cancer agents with attractive co-adjuvant properties.”

https://pubmed.ncbi.nlm.nih.gov/40345424/

https://www.sciencedirect.com/science/article/pii/S0014299925004662?via%3Dihub

A novel antioxidant and anti-inflammatory carboxymethylcellulose/chitosan hydrogel loaded with cannabidiol promotes the healing of radiation-combined wound skin injury in the 60Co γ-irradiated mice

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“Background: Combined radiation and wound skin injury (RW) are frequently observed in patients undergoing tumor surgery plus radiotherapy, and but specific treatment is lacking. Chitosan (CS) and carboxymethyl cellulose (CMC) are commonly used to prepare hydrogel with good biocompatibility and low toxicity.

Cannabidiol (CBD) has presented anti-inflammatory, antioxidant, and neuroprotective properties.

Methods: CMC, CS, and CBD were used and designed for three types of hydrogels (CMC/CS2/CBD, CMC/CS3/CBD, CMC/CS4/CBD) with different ratios of CMC and CS based on previous report and our preliminary experiments. The CMC/CS/CBD hydrogel was synthesized using electrostatic interaction without chemical crosslinking, characterized via fourier transform infrared (FT-IR), and tested for mechanical properties, swelling behavior, biocompatibility, antioxidant activity, cytotoxicity, and hemocompatibility. 60Co γ irradiation (5 Gy, 0.62 Gy/min) combined with 1 cm circular trauma was applied to establish RW mice model. Topical applications of CMC/CS3, CMC/CS2/CBD, CMC/CS3/CBD were used to treat RW injury once a day for 10 consecutive days. The mice were euthanized 7, 14, 21 days after radiation, and samples were collected.

Results: FT-IR confirmed the successful formation of a polyelectrolyte network. The CMC/CS3/CBD hydrogel exhibited optimal mechanical strength, rapid gelation, high swelling capacity, and excellent biocompatibility. Both CMC/CS2/CBD and CMC/CS3/CBD hydrogels effectively improved RW injury 7, 14, 21 days after radiation. Reduced inflammation and increased collagen production were observed the two groups. The significant increased expression of interleukin (IL)-1β, IL-22, IL-17A, IL-6, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, CC motif chemokine ligand (CCL)2, CCL3, CCL4, CCL5, CCL11 in the RW group was greatly inhibited after treatment with CMC/CS3/CBD hydrogel. Transcriptome analysis revealed the hydrogel’s impact on lipid metabolism and epithelial differentiation pathways.

Conclusions: By integrating CBD into a CMC/CS-based hydrogel without using toxic crosslinkers, this study provides a novel, biomaterial-based, biocompatible approach for RW injury. These findings pave the way for future clinical application of CMC/CS3/CBD hydrogel in RW injury.”

https://pubmed.ncbi.nlm.nih.gov/40318533/

“We developed an injectable CMC/CS/CBD hydrogel for the treatment of RW injuries. The hydrogel was fabricated via electrostatic self-assembly, eliminating the need for toxic chemical crosslinkers, exhibiting excellent biocompatibility and low cytotoxicity. Our work firstly integrated CBD into a hydrogel matrix specifically for RW treatment, and confirmed its ability to suppress inflammation and regulate macrophage polarization.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711325004283?via%3Dihub

Efficacy of a Neuroimmune Therapy Including Pineal Methoxyindoles, Angiotensin 1-7, and Endocannabinoids in Cancer, Autoimmune, and Neurodegenerative Diseases

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“Purpose: Recent advancements in psycho-neuro-endocrine-immunology indicate that numerous noncommunicable diseases (NCDs) originate from disruptions in the cytokine immune network, resulting in chronic inflammatory responses. This persistent low-degree inflammation is attributed to deficiencies in crucial endogenous anti-inflammatory neuroendocrine systems, including the pineal gland, the endocannabinoid system, and the angiotensin-converting enzyme 2 / angiotensin 1-7 axis.

The administration of pineal methoxyindoles (melatonin, 5-methoxytryptamine), cannabinoids, and angiotensin 1-7 may entail potential therapeutic benefits for NCDs, particularly for patients who do not respond to conventional treatments.

Patients and methods: This study evaluates the safety and efficacy of a neuroimmune regimen comprising melatonin (100 mg/day at night), 5-methoxytryptamine (30 mg in the early afternoon), angiotensin 1-7 (0.5 mg twice daily), and cannabidiol (20 mg twice daily) in 306 patients with NCDs, including advanced cancer, autoimmune diseases, neurodegenerative disorders, depression, and cardiovascular disease.

Results: The neuroimmune regimen successfully halted cancer progression in 68% of cancer patients, who also reported improvements in mood, sleep, and relief from anxiety, pain, and fatigue. In patients with autoimmune diseases, the treatment effectively controlled the disease process, remarkable in cases of multiple sclerosis. Additionally, positive outcomes were observed in patients with Parkinson’s disease, Alzheimer’s disease, and depression.

Conclusion: Randomized controlled trials are required to assess this therapeutic approach for NCDs that includes endogenous neuroendocrine molecules regulating immune responses in an anti-inflammatory manner.”

https://pubmed.ncbi.nlm.nih.gov/40330271/

“This study highlights the potential of leveraging endogenous molecules to treat NCDs by modulating cell proliferation, inflammation, immune responses, metabolism, and neurological functions. The findings suggest that a neuroimmune regimen incorporating melatonin, angiotensin 1–7, and other bioactive compounds could offer a low-cost, minimally toxic therapeutic approach.”

https://www.dovepress.com/efficacy-of-a-neuroimmune-therapy-including-pineal-methoxyindoles-angi-peer-reviewed-fulltext-article-CIA

Cannabidiol potentiates p53-driven autophagic cell death in non-small cell lung cancer following DNA damage: a novel synergistic approach beyond canonical pathways

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“The search for more effective and safer cancer therapies has led to an increasing interest in combination treatments that use well-established agents.

Here we explore the potential of cannabidiol (CBD), a compound derived from cannabis, to enhance the anticancer effects of etoposide in non-small cell lung cancer (NSCLC). Although CBD is primarily used to manage childhood epilepsy, its broader therapeutic applications are being actively investigated, particularly in oncology.

Our results revealed that, among various tested chemotherapeutic drugs, etoposide showed the most significant reduction in NSCLC cell viability when combined with CBD.

To understand this synergistic effect, we conducted extensive transcriptomic and proteomic profiling, which showed that the combination of CBD and etoposide upregulated genes associated with autophagic cell death while downregulating key oncogenes known to drive tumor progression. This dual effect on cell death and oncogene suppression was mediated by inactivation of the PI3K-AKT-mTOR signaling pathway, a crucial regulator of cell growth and survival, and was found to be dependent on the p53 status.

Interestingly, our analysis revealed that this combination therapy did not rely on traditional cannabinoid receptors or transient receptor potential cation channels, indicating that CBD exerts its anticancer effects through novel, noncanonical mechanisms.

The findings suggest that the combination of CBD with etoposide could represent a groundbreaking approach to NSCLC treatment, particularly in cases where conventional therapies fail. By inducing autophagic cell death and inhibiting oncogenic pathways, this therapeutic strategy offers a promising new avenue for enhancing treatment efficacy in NSCLC, especially in tumors with p53 function.”

https://pubmed.ncbi.nlm.nih.gov/40307570/

“In conclusion, the combination of CBD and etoposide presents a compelling therapeutic strategy for NSCLC, leveraging mechanisms of autophagy, apoptosis and oncogene suppression. These findings not only provide a strong rationale for further exploration in preclinical and clinical settings but also suggest the potential to address key challenges in NSCLC treatment, such as drug resistance and the limitations of existing therapies. Furthermore, this combination therapy holds particular promise for patients with p53 mutations or those who have developed resistance to EGFR inhibitors (for example, osimertinib) or ALK-targeted drugs (for example, alectinib), providing a promising alternative approach for improving the outcomes of patients with NSCLC.”

https://www.nature.com/articles/s12276-025-01444-x

“Etoposide derives from podophyllotoxin, a toxin found in the American Mayapple.”

“Cannabidiol (CBD) is a cannabinoid found in the Cannabis sativa plant.”

The Endocannabinoid System in Cancer Biology: A Mini-Review of Mechanisms and Therapeutic Potential

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“The Endocannabinoid System (ECS) plays a critical role in maintaining physiological homeostasis, influencing a range of processes such as neuroprotection, inflammation, energy metabolism, and immune responses.

Comprising cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and degradation, the ECS has attracted increasing attention in cancer research. Cannabinoid receptor activation has been associated with the regulation of cancer-related processes, including cell proliferation, apoptosis, and angiogenesis, suggesting that the ECS may have a role in tumor progression and cancer treatment.

Preclinical studies have shown that cannabinoids, through their interaction with CB1 and CB2 receptors, can inhibit tumor cell growth, induce programmed cell death, and suppress the formation of new blood vessels in various cancer models.

Despite these encouraging findings, the clinical translation of ECS-targeted therapies remains in its early stages. The complexity of tumor heterogeneity, the variability in patient responses, and the challenges associated with the pharmacokinetics of cannabinoids are significant obstacles to the broader application of these findings in clinical settings.

This review provides an overview of the current understanding of the ECS’s involvement in cancer biology, focusing on key mechanisms by which it may influence carcinogenesis. Additionally, we discuss the therapeutic potential of targeting the ECS in cancer treatment, while highlighting the limitations and uncertainties that need to be addressed through ongoing research.”

https://www.frontiersin.org/journals/oncology-reviews/articles/10.3389/or.2025.1573797/abstract

New Cannabinoids and Chlorin-Type Metabolites from the Flowers of Cannabis sativa L.: A Study on Their Neuroblastoma Activity

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“Background/Objectives: Cannabis sativa has been utilized for medical purposes for thousands of years. It continues to be recognized as a plant with an extensive variety of medicinal and nutraceutical uses today. In this study, a chemical investigation of the flowers of C. sativa isolated by using a variety of chromatographic techniques led to the isolation of eleven compounds. These purified compounds were evaluated for antitumor activity against SK-N-SH neuroblastoma cells. 

Methods: The compounds were isolated by using chromatographic techniques. Their structures were identified by the examination of spectroscopic methods, including 1D (1H, 13C, and DEPT) and 2D (COSY, HSQC, HMBC, and NOESY) nuclear magnetic resonance (NMR) spectra and mass spectrum, together with the comparison to those reported previously in the literature. The evaluation of toxicity on SK-N-SH cells was performed by the MTT method. 

Results: Eleven compounds were isolated from the flowers of C. sativa, including two new compounds, namely cannabielsoxa (1), 132-hydroxypheophorbide c ethyl ester (2), and six known cannabinoids (6–11), together with the first isolation of chlorin-type compounds: pyropheophorbide A (3), 132-hydroxypheophorbide b ethyl ester (4), and ligulariaphytin A (5) from this plant. The results also demonstrated that cannabinoid compounds had stronger inhibitory effects on neuroblastoma cells than chlorin-type compounds. 

Conclusions: The evaluation of the biological activities of compounds showed that compounds 4–10 could be considered as the potential compounds for antitumor effects against neuroblastomas. This is also highlighted by using docking analysis. Additionally, the results of this study also suggest that these compounds have the potential to be developed into antineuroblastoma products.”

https://pubmed.ncbi.nlm.nih.gov/40283956/

“This reinforces confidence that a cannabis extract enriched in cannabinoids has the potential to be a promising candidate for neuroblastoma treatment.”

https://www.mdpi.com/1424-8247/18/4/521

Cannabidiol as a novel therapeutic agent in breast cancer: evidence from literature

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“Background: Breast cancer is one of the most prevalent cancers worldwide, posing significant challenges due to its heterogeneity and the emergence of drug resistance. Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has recently gained attention for its potential therapeutic effects in breast cancer.

Objective: This review aims to evaluate the antitumor effects of CBD in breast cancer treatment by synthesizing preclinical and clinical evidence, elucidating its mechanisms of action, and exploring its translational potential.

Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive search was performed across PubMed, Google Scholar, Web of Science, and Scopus databases, using keywords such as “Cannabidiol,” “CBD,” “Breast Cancer,” “Therapeutic Agent,” and “Antitumor Effects.” A total of 1,191 articles were initially identified. After duplicate removal and eligibility screening, 34 studies published between 1998 and 2025 were selected, including in vitro, in vivo, and clinical investigations. Studies were assessed based on PRISMA recommendations, considering inclusion criteria such as CBD’s impact on apoptosis, cell proliferation, tumor progression, and molecular mechanisms.

Results: CBD demonstrated significant anticancer effects, including induction of apoptosis, inhibition of cell proliferation, suppression of metastasis, and modulation of the tumor microenvironment. Mechanistically, CBD modulates key pathways such as PI3K/Akt, mTOR, and PPARγ and interacts with CB1, CB2, and non-cannabinoid receptors. Preclinical studies showed CBD’s efficacy, particularly in triple-negative breast cancer (TNBC), while limited clinical trials highlighted its potential as an adjunct to conventional therapies.

Conclusion: CBD offers a promising therapeutic approach for breast cancer, especially for aggressive subtypes like TNBC. However, challenges such as variability in study design, lack of standardized protocols, and limited clinical validation hinder its clinical application. Future research should focus on conducting robust clinical trials, identifying predictive biomarkers, and optimizing combinatorial therapies to integrate CBD into personalized cancer treatment strategies.”

https://pubmed.ncbi.nlm.nih.gov/40275168/

“CBD holds significant promise as a complementary or standalone therapeutic agent in breast cancer treatment, particularly in TNBC, where conventional options are limited. However, clinical validation through well-designed trials, biomarker identification, and safety profiling remains imperative before widespread clinical adoption. Future studies should focus on optimizing combinatorial therapies, investigating long-term effects, and refining pharmacological formulations to bridge the gap between preclinical findings and clinical application. By addressing these challenges, CBD could potentially redefine breast cancer management strategies, offering a safer, more effective, and targeted approach to treatment.”

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14175-z

Research mapping of cannabinoids and endocannabinoid system in cancer over the past three decades: insights from bibliometric analysis

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“Background: The cannabinoids and endocannabinoid system are thought to play critical roles in multiple signaling pathways in organisms, and extensive evidence from preclinical studies indicated that cannabinoids and endocannabinoids displayed anticancer potential. This study aimed to summarize the research of cannabinoids and endocannabinoid system in cancer through bibliometric analysis.

Methods: Relevant literature in the field of cannabinoids and endocannabinoid system in cancer published during 1995-2024 were collected from the Web of Science Core Collection database. VOSviewer and SCImago Graphica were applied to perform bibliometric analysis of countries, institutions, authors, journals, documents, and keywords.

Results: A total of 3,052 publications were identified, and the global output exhibited a generally upward trend over the past 3 decades. The USA had the greatest number of publications and citations in this research field. Italian National Research Council led in terms of publication, while Complutense University of Madrid had the highest total citations. Vincenzo Di Marzo was the leading author in this field with the greatest number of publications and citations. The co-occurrence of keywords revealed that the research frontiers mainly included “cannabinoids”, “endocannabinoid system”, “cancer”, “anandamide”, “cannabidiol”, “cannabinoid receptor”, “apoptosis”, and “proliferation”.

Conclusion: Our results revealed that the research of cannabinoids and endocannabinoid system in cancer would receive continuous attention. The USA and Italy have made remarkable contributions to this field, supported by their influential institutions and prolific scholars. The research emphasis has evolved from basic functional characterization to mechanistic exploration of disease pathways and translational applications within multidisciplinary framework.”

https://pubmed.ncbi.nlm.nih.gov/40242437/

“In this study, we conducted a comprehensive bibliometric analysis on the research of cannabinoids and endocannabinoid system in cancer over the past 3 decades. Our results would provide referable guidance for the understanding of research emphasis on this topic, offering insights for clinical interventions and scientific inquiries.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1540619/full

Meta-analysis of medical cannabis outcomes and associations with cancer

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“Background: Growing bodies of evidence suggest that cannabis may play a significant role in both oncological palliative care and as a direct anticarcinogenic agent, but classification as a Schedule I substance has complicated research into its therapeutic potential, leaving the state of research scattered and heterogeneous. This meta-analysis was conducted to determine the scientific consensus on medical cannabis’ viability in cancer treatment.

Objective: The aim of this meta-analysis was to systematically assess the existing literature on medical cannabis, focusing on its therapeutic potential, safety profiles, and role in cancer treatment.

Methods: This study synthesized data from over 10,000 peer-reviewed research papers, encompassing 39,767 data points related to cannabis and various health outcomes. Using sentiment analysis, the study identified correlations between cannabis use and supported, not supported, and unclear sentiments across multiple categories, including cancer dynamics, health metrics, and cancer treatments. A sensitivity analysis was conducted to validate the reliability of the findings.

Results: The meta-analysis revealed a significant consensus supporting the use of medical cannabis in the categories of health metrics, cancer treatments, and cancer dynamics. The aggregated correlation strength of cannabis across all cancer topics indicates that support for medical cannabis is 31.38× stronger than opposition to it. The analysis highlighted the anti-inflammatory potential of cannabis, its use in managing cancer-related symptoms such as pain, nausea, and appetite loss, and explored the consensus on its use as an anticarcinogenic agent.

Discussion: The findings indicate a strong and growing consensus within the scientific community regarding the therapeutic benefits of cannabis, particularly in the context of cancer. The consistent correlation strengths for cannabis as both a palliative adjunct and a potential anticarcinogenic agent redefine the consensus around cannabis as a medical intervention.

Conclusion: The consistency of positive sentiments across a wide range of studies suggests that cannabis should be re-evaluated within the medical community as a treatment option. The findings have implications for public health research, clinical practice, and discussions surrounding the legal status of medical cannabis. These results suggest a need for further research to explore the full therapeutic potential of cannabis and address knowledge gaps.”

https://pubmed.ncbi.nlm.nih.gov/40303989/

“The data presented here indicate that cannabis has a well-established role in managing symptoms related to cancer and may have both direct and indirect anticancer properties, which challenges the notion that it has no accepted medical use.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1490621/full