Category Archives: Cancer

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.”

“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

Effect of cannabinoids on the efficacy and side effects of anticancer therapeutic strategies – Current status of preclinical and clinical research

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“Cannabinoids have attracted increasing attention in cancer research in recent decades. A major focus of current preclinical and clinical studies is on the interactions and potential risks when combined with chemotherapeutic agents, targeted therapies and other anticancer strategies.

Given the extensive preclinical data on additive, synergistic and, in some cases, antagonistic tumor cell killing effects of chemotherapeutic agents and cannabinoids when co-administered, a critical analysis of these data seems essential. The available data mainly relate to combination treatments for glioblastoma, hematological malignancies and breast cancer, but also for other cancer types.

Such an analysis also appears necessary because cannabinoids are used as an option to treat nausea and vomiting caused by chemotherapy, as well as tumor-related pain, and cancer patients sometimes take cannabinoids without a medical prescription. In addition, numerous recent preclinical studies also suggest cannabinoid-mediated relief of other chemotherapy-related side effects such as peripheral neuropathy, nephrotoxicity, cardiotoxicity, cystitis, bladder complications and mucositis.

To summarize, the data available to date raise the prospect that cannabinoids may increase the efficacy of chemotherapeutic agents while reducing their side effects. However, studies on interactions are mostly limited to cytotoxicity analyses. An equally thorough investigation of the effects of such combinations on the immune system and on the tumorigenic levels of angiogenesis, invasion and metastasis is still pending. On this basis, a comprehensive understanding for the evaluation of a targeted additional treatment of various cancers with cannabinoids could be established.”

https://pubmed.ncbi.nlm.nih.gov/40221102/

“The anticancer effect of various phytocannabinoids, including Δ9-tetrahydrocannabinol (THC), was first demonstrated in animal experiments in 1975 (Munson, Harris, Friedman, Dewey, & Carchman, 1975). After the discovery of the endocannabinoid system in the early 1990s, these effects were confirmed in numerous preclinical studies in a variety of different neoplastic entities. Based on these findings and studies demonstrating the anticancer effects of cannabinoids on various hallmarks of tumorigenesis, cannabinoids have increasingly become the focus of scientific discussions as systemic tumor therapies in recent years (for an overview, see Ramer & Hinz, 2015; Hinz & Ramer, 2019). From a preclinical point of view, the systemic antitumor effects of cannabinoids thus represent the basis for combining cannabinoids with chemotherapies, which can increase the effectiveness of chemotherapeutic agents and overcome resistance.”

https://www.sciencedirect.com/science/article/abs/pii/S0163725825000634?via%3Dihub

Effects of cannabinoids on immune checkpoint inhibitor response: CCTG pooled analysis of individual patient data

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“Background: Immune checkpoint inhibitors (ICIs) benefit patients across various tumor types. ICIs block cancer and T-cell interactions whereas cannabinoids may inhibit T-cell activation, reducing lysis of tumor cells. Interactions between cannabinoid use and dual ICI treatment remain unknown.

Methods: Individual patient data from 4 Canadian Cancer Trials Group (CCTG) trials of patients treated with dual ICI ± chemotherapy (n = 684) were pooled. Cochran – Mantel – Haenszel and log-rank tests (stratified by trial/treatment arms) correlated cannabinoid use with clinicopathologic characteristics, Best Overall Response (BOR)/iBOR per RECIST 1.1/iRECIST, Progression-Free Survival (PFS)/iPFS, Overall Survival (OS) and immune-related adverse events (irAEs).

Results: Sixty-five (9.5%) patients took cannabinoids at any time on trial, 32 (4.7%) of which were using cannabinoids at baseline. By multivariate analysis, cannabinoid use at baseline was significantly associated with improved iPFS (0.05), but not iBOR (p = 0.15), PFS (p = 0.12), OS (p = 0.35) or incidence of grade 1/2 or 3/4 irAEs (p = 0.96 and 0.65 respectively). Results were not significantly different with cannabinoid use at any time on trial.

Conclusion: Improved iPFS with cannabinoid use in patients treated with durvalumab plus tremelimumab ± chemotherapy did not translate into OS benefits. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://pubmed.ncbi.nlm.nih.gov/40184324/

“Plain Language Summary

Immune checkpoint inhibitors (ICI) have become an important treatment option for cancer patients and has been associated with improved survival outcomes across various tumor types. Cannabinoids are active components of cannabis and include tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis use has increased in Canadian cancer patients and is often used for symptom management. Some studies have suggested that cannabinoids can alter the function of the immune system, which could impact the effectiveness of immune checkpoint inhibitors. Therefore, we aimed to evaluate whether cannabinoid use might impact the effectiveness of combination ICI treatment with durvalumab plus tremelimumab (with/without chemotherapy) using data from four clinical trials completed through the Canadian Cancer Trials Group (CCTG). We found no significant difference in response, survival outcomes or adverse events in patients who used cannabinoids with combination ICI treatment compared to cannabinoid non-users. This study supports the safe use of cannabinoids in the context of combination ICI therapy.”

https://www.tandfonline.com/doi/full/10.1080/1750743X.2025.2485012

Cannabidiol from Conventional to Advanced Nanomedicines for the Management of Cancer-Associated Pain

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“Chemotherapy-induced pain is one of the major challenges that hamper the patient’s quality of life. Several cases of insufficient pain management were reported globally, especially in the case of patients who do not respond well to conventional pain management regimes and opioid analgesics. Additionally, conventional pain management has several shortcomings, and evidence suggests that cannabidiol has the potential to overcome those shortcomings.

Cannabidiol (CBD) is a non-psychoactive compound of the Cannabis plant that shows an effective outcome in chemotherapy- induced pain as well as in cancer treatment, as it possesses anti-inflammatory and analgesic properties.

The mechanism of pain and its management by cannabidiol, with all possible evidence, is well summarised in the paper. This article concludes the types of pain experienced by cancer patients, the effectiveness of CBD in the management of pain, and challenges faced by patients after using Cannabidiol with various case studies.

Later, antitumor efficacy studies of CBD were disclosed, and its various types of formulations and nano-formulations were summarized in the paper. Overall, the paper establishes the role of cannabidiol in Chemotherapy-induced pain.”

https://pubmed.ncbi.nlm.nih.gov/40151084/

https://www.eurekaselect.com/article/147414

Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance

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“Cell death is a fundamental process that needs to be maintained to balance cellular functions and prevent disease. There are several cell death pathways; however, apoptosis and parthanatos are the most prominent and have important roles in cancer biology. As an extremely well-regulated process, apoptosis removes damaged or abnormal cells via caspase activation and mitochondrial involvement.

Unlike in the healthy cells, the loss of ability to induce apoptosis in cancer permits tumor cells to survive and multiply out of control and contribute to tumor progression and therapy resistance. On the contrary, parthanatos is a caspase-independent metabolic collapse driven by poly (ADP-ribose) polymerase 1 (PARP1) overactivation, translocation of apoptosis-inducing factor (AIF), and complete DNA damage. Several cancer models are involved with parthanatos. Deoxypodophyllotoxin (DPT) induces parthanatos in glioma cells by excessive ROS generation, PARP1 upregulation, and AIF nuclear translocation.

Like in acute myeloid leukemia (AML), the cannabinoid derivative WIN-55 triggers parthanatos, and the effects can be reversed by PARP inhibitors such as olaparib.

Developing cancer treatment strategies involving advanced cancer treatment strategies relies on the interplay between apoptosis and parthanatos. However, such apoptosis-based cancer therapies tend to develop resistance, so there is an urgent need to look into alternative pathways like parthanatos, which may not always trigger apoptosis.

In overcoming apoptosis resistance, there is evidence that combining apoptosis-inducing agents, such as BH3 mimetics, with PARP inhibitors synergistically enhances cell death.

Oxidative stress modulators have been found to promote the execution of parthanatic and apoptotic pathways and allow treatment. In this review, apoptosis and parthanatos are thoroughly compared at the molecular level, and their roles in cancer pathogenesis as related to cancer therapeutic potential are discussed.

We incorporate recent findings to demonstrate that not only can parthanatos be used to manage therapy resistance and enhance cancer treatment via the combination of parthanatos and apoptosis but also that immunity and bone deposition can feasibly be employed against long-circulating cancer stem cells to treat diverse forms of metastatic cancers.”

https://pubmed.ncbi.nlm.nih.gov/40166425/

“Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.”

https://pubmed.ncbi.nlm.nih.gov/38461169/

Early oral administration of THC:CBD formulations prevent pain-related behaviors without exacerbating paclitaxel-induced changes in weight, locomotion, and anxiety in a rat model of chemotherapy-induced neuropathy

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“Rationale: Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.

Objectives: Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.

Methods: The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.

Results: Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuated weight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.

Conclusions: Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/40163146/