Category Archives: Cancer

Ewing sarcoma-related pain: potential role of medical cannabis monotherapy in symptom management – a case report

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“Persistent, multimodal cancer pain remains a challenge, particularly in long-term survivors facing treatment-related complications. The management of high-dose opioid dependence concurrent with chronic, multi-drug resistant (MDR) periprosthetic infection presents a critical unmet need. This case reports the potential use and sustained efficacy of medical cannabis monotherapy, highlighting an unexpected temporal association with the resolution of inflammatory and infectious symptoms in a highly complex oncologic setting.

Case presentation

A 27-year-old male, a long-term survivor of high-risk Ewing Sarcoma of the proximal tibia, presented with intractable mixed pain (VAS 9–10) secondary to chronic, recurrent MDR periprosthetic osteomyelitis and multiple surgical revisions (2013–2024). Despite continuous use of high-dose opioids (up to 120 mg/day morphine equivalents), pain levels remained moderate-to-severe (VAS 6–7) and functional status was poor. The patient had previously found temporary relief with self-administered cannabis. In January 2025, after refusing limb amputation, supervised medical cannabis therapy (Bedrocan®, 22% THC, 1% CBD, 1 g/day) was initiated. Pain levels gradually stabilized at VAS 2–3, coinciding with complete opioid discontinuation within four weeks. Over nine months of follow-up, the patient maintained full autonomy and an active lifestyle. Notably, sustained cannabis monotherapy was associated with the complete closure of the chronic draining fistula and a reduction in systemic inflammatory markers (CRP from 9.6 to 2.3 mg/dL). No significant adverse effects were reported.

Conclusions

This case suggests that THC-rich medical cannabis may represent a feasible strategy for achieving opioid-free analgesia in selected patients with refractory oncologic pain. While causality cannot be established from a single observation, the correlation between cannabis initiation and the resolution of severe chronic inflammatory and infectious symptoms is intriguing and suggests a potential pleiotropic role extending beyond traditional pain management. While these findings align with emerging evidence highlighting the potent immunomodulatory and anti-inflammatory properties of cannabinoids, they contrast with some recent neutral meta-analyses in broader populations, an this would justify warrant urgent controlled investigation into the potential mechanisms of cannabinoids in complex inflammatory pain states and their role as a possible adjunct in managing long-term oncological complications.”

https://pubmed.ncbi.nlm.nih.gov/41572388

https://link.springer.com/article/10.1186/s42238-026-00388-x

Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma

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“Hepatocellular carcinoma (HCC) is the main type of liver cancer and one of the malignancies with the highest mortality rates worldwide. HCC is associated with diverse etiological factors including alcohol use, viral infections, fatty liver disease, and liver cirrhosis (a major risk factor for HCC). Unfortunately, many patients are diagnosed at advanced stages of the disease and receive palliative treatment only. Therefore, early markers of HCC and novel therapeutic approaches are urgently needed.

The endocannabinoid system is involved in various physiological processes such as motor coordination, emotional control, learning and memory, neuronal development, antinociception, and immunological processes. Interestingly, endocannabinoids modulate signaling pathways involved in cell survival, proliferation, apoptosis, autophagy, and immune response.

Consistently, several cannabinoids have demonstrated potential antitumor properties in experimental models.

The participation of metabotropic and ionotropic cannabinoid receptors in the biological effects of cannabinoids has been extensively described. In addition, cannabinoids interact with other targets, including several ion channels. Notably, several ion channels targeted by cannabinoids are involved in inflammation, proliferation, and apoptosis in liver diseases, including HCC.

In this literature review, we describe and discuss both the endocannabinoid system and exogenous phytocannabinoids, such as cannabidiol and Δ9-tetrahydrocannabinol, along with their canonical receptors, as well as the cannabidiol-targeted ion channels and their role in liver cancer and its preceding liver diseases. The cannabidiol-ion channel association is an extraordinary opportunity in liver cancer prevention and therapy, with potential implications for several environments that are for the benefit of cancer patients, including sociocultural, public health, and economic systems.”

https://pubmed.ncbi.nlm.nih.gov/41562849

“The endocannabinoid system (ECS) plays a crucial role in the development and functioning of several biological systems. Classically, the endocannabinoid system comprises receptors, endogenous ligands, and enzymes that synthesize, transport, and degrade such ligands. ECS regulates many biological processes, both in normal conditions like brain function, neurotransmitter release, sleep regulation, appetite, movement, and coordination, as well as pathological states such as neurodegenerative disorders, headaches, chronic pain, anxiety, depression, and cancer, among others.

Accordingly, pharmacological modulation of the endocannabinoid system may be a potential target for preventing disease progression or enhancing symptom relief in multiple conditions, including cancer “

“Dysregulation of voltage-gated sodium channels causes the development of several diseases. CBD is a non-selective Nav1.1–1.7 sodium channel inhibitor and is effective in the treatment of epilepsy.”

“Exploiting the cannabidiol-ion channel-transporters association represents an extraordinary opportunity for liver cancer prevention and therapy, which may help to reduce the high mortality from this malignancy and to involve sociocultural, public health, regulatory, and economic systems.”

“Taken together, preclinical, epidemiological, and clinical data converge to support CBD as a promising candidate for the prevention and management of liver diseases and HCC, with potential implications for sociocultural, public health, and economic systems.”

https://www.mdpi.com/1873-149X/33/1/8

Therapeutic potential of acidic cannabinoids: an update

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“Cannabis sativa yields a wide range of bioactive compounds, including terpenes, flavonoids, and cannabinoids.

Tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), and cannabichromenic acid (CBCA) are the acidic biosynthetic precursors of the neutral cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which have been the subject of much research.

This review examines the biosynthesis, decarboxylation, molecular pharmacology, and therapeutic significance of acidic cannabinoids, intending to address a significant knowledge gap. Peer-reviewed literature from major scientific databases was used in a systematic narrative review with an emphasis on investigations of acidic cannabinoid chemistry, pharmacology, pharmacokinetics, and disease-specific applications.

According to the reviewed data, acidic cannabinoids exhibit unique biological activities that distinguish them from their neutral counterparts. These include neuroprotective, anti-inflammatory, anticonvulsant, and anti-proliferative actions, which are mediated by molecular targets such as serotonin 5-HT1A receptors, cyclooxygenase-2 (COX-2), transient receptor potential (TRP) channels, and peroxisome proliferator-activated receptor-γ (PPARγ).

Acidic cannabinoids are more appealing for therapeutic usage in children and the elderly, considering that they are not intoxicating like THC; however, this distinction applies primarily to non‑heated consumption. Chemical instability, low bioavailability, and a dearth of controlled human trials impede clinical translation despite their potential.

According to the findings, acidic cannabinoids are an underutilized yet potentially valuable class of precision medicines.

In this study, we outline existing understanding on acidic cannabinoids, discuss their production and transformation, and identify research needs that could influence cannabis science research.”

https://pubmed.ncbi.nlm.nih.gov/41545891

https://link.springer.com/article/10.1186/s42238-026-00387-y

“Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis”

https://pmc.ncbi.nlm.nih.gov/articles/PMC7409346


The differential effects of CBD and CBDA on viability and mRNA expression in colorectal cancer cells

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“Background: Cannabinoids have attracted significant attention for their potential therapeutic application in cancer research. However, recent studies have reported antitumor activity of cannabidiolic acid (CBDA)-the acidic precursor of CBD-in breast cancer cells, involving modulation of cyclooxygenase signaling. To our knowledge, no investigations have examined the effects of CBDA on RNA expression and signaling pathways in colorectal cancer (CRC) cells. Therefore, we aimed to investigate the effects of CBD, CBDA, and a CBDA-rich Cannabis sativa (C.s). extract on the growth and gene expression in CRC cell lines.

Methods: We assessed cell viability and clonogenic growth of the CRC cell lines HCT116 and DLD1 following treatment with pure CBD, pure CBDA, a CBDA-rich C.s. extract (CBDA/CBD ratio 20:1), and a corresponding mixture of pure CBDA/CBD. RNA sequencing was performed to analyze differentially expressed genes (DEGs) and the cell signaling pathways affected by these treatments.

Results: Of all tested compounds, CBD exhibited the strongest cytotoxic effect in both cell lines, whereas CBDA demonstrated minimal toxicity, particularly in HCT116 cells. Furthermore, we observed a greater inhibitory effect of the CBDA-rich C.s. extract on HCT116 cell growth compared to the CBDA/CBD mixture. RNA sequencing analysis revealed that CBD had the most pronounced impact on gene expression, while CBDA had the least. Notably, treatment with the C.s. extract resulted in a higher number of DEGs than the CBDA/CBD mixture in HCT116. Gene expression analysis indicated an upregulation of the Wnt and Hippo signaling pathways following CBD treatment. Additionally, CBDA, CBD/CBDA (1:20), and the C.s. extract primarily induced metabolic processes in DLD1 cells, suggesting a distinct metabolic response.

Conclusion: Our findings showed that CBD exerts stronger effects on cell survival and gene expression in CRC cells than CBDA, which showed only limited activity. Moreover, the CBDA-rich C.s. extract exhibited greater efficacy than the CBDA/CBD mixture. More research is needed to further elucidate the impact of cannabinoids on CRC cell biology and signaling pathways.”

https://pubmed.ncbi.nlm.nih.gov/41546069

https://link.springer.com/article/10.1186/s42238-026-00391-2

Cannabidiol Inhibits Melanoma Progression by Regulating PPARγ-TET1 Complex-dependent LRASM1 Demethylation

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“Melanoma represents one of the most aggressive forms of skin cancers, with advanced metastatic stages largely managed through chemotherapy. However, current therapeutic strategies remain limited by drug resistance and systemic toxicity. Cannabidiol (CBD), the primary nonpsychoactive constituent of Cannabis sativa, has recently attracted attention for its anticancer properties across multiple tumor types.

OBJECTIVES

This study aimed to explore the antitumor efficacy of CBD in melanoma and elucidate its underlying molecular mechanisms, with the goal of identifying novel therapeutic strategies to overcome resistance and reduce adverse effects associated with conventional treatments.

METHODS

The antiproliferative and pro-apoptotic effects of CBD were assessed in vitro using MTS, EdU, Transwell invasion, and flow cytometry. In vivo efficacy was evaluated using a murine lung metastasis model. Potential CBD targets in melanoma were identified through network pharmacology and molecular docking, with a focus on peroxisome proliferator-activated receptor γ (PPARγ) and validation by western blotting and immunofluorescence. Integrated transcriptomic and genome-wide methylation analyses were performed to investigate epigenetic modifications induced by CBD. Co-immunoprecipitation and chromatin immunoprecipitation assays were employed to detect the interaction between PPARγ and ten-eleven translocation 1 (TET1), including their binding to promoter regions of downstream factors. Methylation-regulated target genes were further validated using qPCR and MeDIP PCR.

RESULTS

CBD significantly induced apoptosis and inhibited cell proliferation and invasion of melanoma cells in vitro, while reducing pulmonary metastasis in vivo. Pharmacological and molecular docking analyses, supported by protein-level validation, identified PPARγ as a critical mediator of CBD activity. Transcriptomic and methylation analyses revealed that CBD modulated global DNA methylation patterns, partly through the formation of a PPARγ-TET1 complex. This complex regulated the demethylation of leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1), a newly identified anticancer gene whose upregulation markedly enhanced melanoma cell apoptosis and suppressed proliferation.

CONCLUSIONS

CBD exhibited strong antitumor activity in melanoma by modulating the PPARγ–TET1 complex to induce demethylation of LRSAM1, thereby suppressing tumor progression. These findings identify CBD as a promising candidate for melanoma therapy.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711326000127

“In summary, this study investigated molecular targets and mechanisms by which CBD suppresses melanoma progression, emphasizing its role in PPARγ activation and epigenetic regulation. These findings establish a mechanistic basis and provide candidate targets for future clinical application of CBD in melanoma treatment.”

“This study provides the first evidence that CBD inhibits melanoma progression by modulating gene methylation. The identification of LRSAM1 as a PPARγ-TET1-regulated tumor suppressor expands current understanding of epigenetic regulation in melanoma and highlights LRSAM1 as a viable therapeutic target.”

https://www.scilit.com/publications/50c9c0a6d08f7880cebb9c69a2c3fca7

Phytocannabinoids influence phospholipid metabolism of melanoma cells: Modulation of in vitro effects of the UVA irradiation

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“The high metastatic potential of melanoma and its poor prognosis in advanced stages motivate the search for innovative therapeutic approaches. Therefore, this study aimed to assess the effects of phytocannabinoids (cannabidiol-CBD, and cannabigerol-CBG) on the structure and function of the melanoma cell membrane, phospholipid metabolism, and the respective metabolites generated in ROS- and enzyme-dependent reactions.

Biochemical and physicochemical parameters were analyzed in melanoma cells (SK-MEL-5) cultured for 24 h with CBD (5 µM), CBG (1 µM), and their combination applied either alone or after UVA irradiation (365 nm) at a dose of 18 J/cm².

Phytocannabinoids have been shown to partially counteract changes in the levels of cell membrane components, including phospholipid polyunsaturated fatty acids (PUFAs) and sialic acid, consequently affecting surface charge density and lipid rafts, which may be a potential target for anticancer therapy. Furthermore, by changing the activity of lipolytic enzymes (PLA2/COX1/2/LOX-5), phytocannabinoids partially enhanced the UVA-induced decrease in free PUFAs. Consequently, the levels of lipid mediators, including endocannabinoids and eicosanoids, were altered.

The use of phytocannabinoids led to a significant increase in 2-AG levels, while the combined action of CBD/CBG reduced the levels of pro-inflammatory eicosanoids. UVA radiation increased the expression of G-protein-coupled receptors in melanoma cells (CB1/2/TRPV1/PPARγ), while the combined use of CBD/CBG reduced their expression.

Therefore, the results have shown that CBD and CBG modulate the metabolism of phospholipids and PUFAs by altering the functions of melanoma cell membranes, potentially offering options for the use of these phytocannabinoids in the integrative biomedicine treatment of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/41529510

“Phytocannabinoids modulate endocannabinoid levels, supporting antitumor activity.”

“In summary, the results of this study indicate that phytocannabinoids (CBD and/or CBG) alter the functionality of melanoma cell membranes by modeling the structure and metabolism of phospholipids and free PUFAs, which may offer potential benefits in integrated melanoma therapy.”

https://www.sciencedirect.com/science/article/pii/S0753332226000351?via%3Dihub

Stability and Degradation-based Proteome Profiling Reveals Cannabidiol as a Promising CDC123-eIF2γ Inhibitor for Colorectal Cancer Therapy

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“Natural products (NPs) have long been foundational in drug discovery, offering unparalleled molecular diversity and complex mechanisms of action. However, identifying molecular targets for NPs remains a significant challenge.

This study introduces stability- and degradation-based proteome profiling (SDPP), which integrates orthogonal principles of thermal stability and degradation activity to enhance target identification precision and expand the NP target landscape, mediating dual regulation of protein stability: extracellularly through small-molecule-binding-induced thermodynamic stabilization and intracellularly via ligand-triggered proteolytic degradation.

Using SDPP, cannabidiol (CBD) is identified as a novel protein-protein interaction (PPI) inhibitor targeting the CDC123-eIF2γ complex, leading to sustained activation of the integrated stress response and apoptosis in colorectal cancer (CRC) cells.

Disruption of the CDC123-eIF2γ complex by CBD offers a selective therapeutic strategy for CRC. Importantly, CDC123 is recognized as an oncogenic driver in CRC, with elevated expression correlating with poor patient prognosis.

These findings establish SDPP as a robust framework for NP target identification and position CBD as a first-in-class natural PPI inhibitor with a promising therapeutic potential.”

https://pubmed.ncbi.nlm.nih.gov/41518300

https://pubs.acs.org/doi/10.1021/jacs.5c20040

Potential Anticancer Effect of Cannabis sativa L. Dichloromethane Extract Through Oxidative Stress-Related Pathways and the Inhibition of the Migration and Invasiveness of Human Breast Cancer Cells (MDA-MB-231 and MCF-7)

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“Breast cancer remains a leading cause of cancer-related morbidity and mortality globally, highlighting the urgent need for novel therapeutic strategies.

This study investigates the molecular mechanisms underlying the anti-proliferative potential of Cannabis sativa dichloromethane extract (C. sativa DCM) on oxidative stress, apoptosis, and invasion in human breast cancer cells.

Key biomarkers, such as antioxidant enzymes (Superoxide Dismutase (SOD) and Glutathione (GSH)), the transcription factor Nrf2, apoptotic proteins (p53, caspase-8 and 9), metalloproteinase (MMP-1 and MMP-9), and Transforming Growth Factor Beta (TGF-β) were examined. Cytotoxicity was assessed using an MTT assay in the MDA-MB-231 and MCF-7 breast cancer cell lines, with comparisons to normal skin fibroblasts (HS27). Oxidative stress biomarkers were quantified using enzymatic assays and ELISA kits, while apoptotic and anti-metastatic factors were determined by Western blotting.

Results demonstrated that C. sativa DCM extract induced significant cell death in a concentration-dependent manner, with IC50 values of 75.46 ± 0.132 μg/mL for MDA-MB-231 and 78.68 ± 0.50 μg/mL for MCF-7 cells. The extract decreased SOD and GSH levels while increasing p53 and caspase activity, confirming apoptosis activation. Additionally, C. sativa DCM inhibited migration and invasion by downregulating MMP-1, MMP-9, and TGF-β. The anti-proliferative potential of C. sativa DCM in breast cancer cells is mediated through a continuous biological pathway involving oxidative stress modulation, apoptotic signaling, and anti-invasive effects. Phytochemical analysis revealed terpenoids and steroids, including compounds like cannabidiol and tetrahydrocannabinol acid.

These findings suggest that C. sativa DCM extract holds potential as an anti-breast cancer therapeutic and warrants further preclinical and clinical investigations.”

https://pubmed.ncbi.nlm.nih.gov/41516029

“Cannabis sativa L., known in many slang languages as marijuana, bhang, ganja, for instance, is an herbaceous species originating from Central Asia and widely distributed around the world. It has been used as a source of fiber, food, oil, and for its multiple curative properties, including anti-parasitic, antipyretic, antibacterial, antitumor, vermifuge, dermatic, and pain-killing properties for centuries. Phytocannabinoids, derived from cannabis, have shown anti-cancer activity in cell lines”

“Based on these research findings, we concluded that C. sativa DCM extract possesses the potential to inhibit the proliferation of breast cancer cells (MCF-7 and MDA-MB-231), while exhibiting minimal cytotoxic effect on normal skin cells Hs27.”

“Given these conclusive findings, the presence of bioactive phytochemicals in C. sativa DCM can be considered as a potential source of anti-cancer agents.”

https://www.mdpi.com/1422-0067/27/1/152


Unlocking the potential: Cannabidiol (CBD) as a promising anti-tumor agent

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“Background: Cannabidiol (CBD), the primary non-psychoactive component of cannabis, is renowned for its antiepileptic, analgesic, and anti-inflammatory properties. Emerging evidence highlights its potential as an anti-tumor agent, yet significant heterogeneity in preclinical studies and an incomplete mechanistic understanding impede its clinical translation.

Purpose: This review aims to systematically evaluate the anti-tumor efficacy, underlying mechanisms, and safety profile of CBD, and to discuss the challenges and future directions for its application in oncology.

Study design: A systematic review.

Methods: We integrated recent high-quality research to assess CBD’s effects across various cancer types. The analysis encompassed its mechanisms in tumor cell biology and the tumor microenvironment (TME), a comparison of monotherapy versus combination therapy efficacy, its role in managing cancer-related symptoms, and its pharmacokinetic/pharmacodynamic properties. Advances in nano-based drug delivery systems were also reviewed.

Results: CBD demonstrates multi-target anti-tumor effects, including inhibiting proliferation, inducing apoptosis, suppressing metastasis, and remodeling the TME via immunomodulation. It exhibits broad-spectrum efficacy in vitro and in vivo, shows synergistic effects in combination therapy, and can alleviate cancer-related symptoms. Safety data indicate a favorable tolerability profile. However, current evidence relies predominantly on preclinical models.

Conclusion: CBD holds substantial promise as an anti-tumor agent. This review provides a theoretical foundation for its rational development. Future work should focus on validating these findings in clinical trials, optimizing targeted drug delivery systems, and establishing standardized treatment protocols.”

https://pubmed.ncbi.nlm.nih.gov/41494497

“CBD, a non-psychoactive phytocannabinoid, has demonstrated therapeutic potential for epilepsy, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Its anti-inflammatory, antioxidant, and anti-necrotic properties, combined with established safety and tolerability in humans, make it a promising therapeutic agent.”

“Recent research has highlighted CBD’s anti-tumor activity across various cancer types. Studies demonstrate that CBD can inhibit migration, induce apoptosis, and suppress proliferation, invasion, metastasis, and angiogenesis in breast, glioma, lung, and colorectal cancers.”

“Cannabidiol (CBD), an FDA-approved and well-tolerated compound, demonstrates promising antitumor effects by inhibiting cancer growth, metastasis, and angiogenesis, while also alleviating cancer-related symptoms such as pain and nausea.”

https://www.sciencedirect.com/science/article/pii/S0944711325013716?via%3Dihub

Cannabidiol suppresses emergency MDSCs generation by disturbing EEF1B2-mediated C/EBP β protein synthesis in colorectal adenomas

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“Background: Colorectal cancer often develops from adenomas over years, necessitating early intervention. Myeloid-derived suppressor cells (MDSCs) are major immune suppressive cell types in colon cancer development from adenomas through early inflammation-induced emergency myelopoiesis. Cannabidiol (CBD) is reported to function in psychosis, coronavirus infection and some cancers through immune regulation. However, its target and underlying mechanisms in colorectal adenomas are unknown.

Methods: The antitumor effect of CBD was validated in two classical colorectal adenomas models including azoxymethane (AOM)/dextran sulfate sodium salt (DSS) induced mice model and high-fat fed Apcmin/+ mice model. Single-cell RNA sequencing was used to identified the immune environment change after CBD treatment in mice colorectal adenomas. Target responsive accessibility profiling was used to find the target of CBD in MDSCs. Subsequently, multiple immunology assays and molecular biology experiment were employed to explore the adenomas prevention mechanisms of CBD.

Results: Here, we found that CBD prevented the incidence of colorectal adenomas in AOM/DSS model and high-fat diet fed Apcmin/+ mice model. Our single-cell RNA sequencing data and the results of immunofluorescence revealed that CBD treatment significantly decreased the number of MDSCs in both two colon adenomas models. Mechanistically, CBD bound to the guanine nucleotide exchange factor domain of EEF1B2, inhibiting its function in translational elongation and subsequent C/EBPβ synthesis. This disruption suppressed the differentiation and generation of MDSCs, leading to enhanced T-cell activation and prevention of colorectal adenoma progression.

Conclusion: Our findings reveal EEF1B2-mediated C/EBPβ protein synthesis as a crucial pathway in MDSC generation and highlight the potential of CBD as an early intervention strategy for colorectal adenomas.”

https://pubmed.ncbi.nlm.nih.gov/41485775

“In this study, we found that CBD prevented the progression of colorectal adenomas via targeting inhibition the function of EEF1B2 to suppress the generation of MDSC from bone marrow in the condition of adenomas induced systemic inflammation. The underlying mechanism was that EEF1B2 inhibition prevented MDSC differentiation and generation through disturbing the protein synthesis of the key transcription factor C/EBPβ.”

“This study implies that CBD may be a potential compound for clinical translation for colorectal adenomas in clinical use, which makes significant therapeutic implications in the early medical intervention for colorectal adenomas and is an effective strategy to inhibit MDSCs generation and relieve immune suppressive environment in MDSCs involved diseases.”

https://jitc.bmj.com/content/14/1/e013081