Category Archives: Cancer

Cytotoxicity of Cannabinoids in Combination with Traditional Lymphoma Chemotherapeutic Drugs Against Non-Hodgkin’s Lymphoma

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“Background: Cannabinoids (CBs) are FDA-approved for mitigating chemotherapy-induced side effects such as pain, nausea, and loss of appetite. Beyond palliative care, CBs exhibit anti-tumor properties in various cancers, including non-Hodgkin’s lymphoma (NHL). Previously, we demonstrated the cytotoxic effect of endogenous and exogenous cannabinoids on human and canine B- and T-cell-type NHL cell lines. The purpose of this study was to establish the cytotoxic effect of cannabinoids in combination with the components of CHOP and lomustine. This traditional NHL chemotherapy regimen comprises cyclophosphamide, doxorubicin, vincristine, and prednisolone. 

Methods: In this study, we studied three cannabinoids, one from each of the three major categories of cannabinoids (endocannabinoid AEA, phytocannabinoid CBD, and synthetic cannabinoid WIN-55 212 22). Each cannabinoid was selected based on potency, as determined in our previous experiments. For the combination, we used five NHL chemotherapy drugs. We analyzed the cytotoxicity of each drug alone and in combinations using canine malignant B-type NHL cell line 1771 and a colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) cell proliferation assay and combination index (CI) based on the Chou-Talalay method. 

Results: Our results demonstrate that the cytotoxic effects of all traditional NHL chemotherapy drugs are synergistically enhanced (interaction with CI < 1) by each of the three cannabinoids at sub-IC50 concentrations. 

Conclusions: This work provides a proof of concept for using cannabinoids and traditional NHL drugs in combination to reduce the dose, and thereby potentially reducing the toxicity, of chemotherapeutic drugs and increasing the survival benefit in lymphoma clinical translation studies, offering a significant advancement in cancer treatment.”

https://pubmed.ncbi.nlm.nih.gov/41595541

https://www.mdpi.com/2227-9059/14/1/3


Cannabidiol as a Prophylactic Agent Against Glioblastoma Growth: A Preclinical Investigation

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“Glioblastoma (GBM) remains one of the most lethal brain tumors, with current therapies offering limited benefits and high relapse rates.

This study presents the first preclinical evidence that pretreatment with inhaled cannabidiol (CBD) before tumor establishment can markedly inhibit GBM progression.

We hypothesized that early CBD exposure could prime the immune and molecular landscape to resist tumor growth. C57BL/6 mice were pretreated with inhaled CBD for 3 or 14 days, or with placebo, prior to intracranial implantation of glioblastoma cells. Tumor growth, immune checkpoint expressions (IDO, PD-L1), and key biomarkers (MGMT, Ki67) were analyzed to evaluate tumor dynamics and immune modulation.

Fourteen-day CBD pretreatment significantly reduced tumor burden compared with both placebo and 3-day CBD groups, accompanied by decreased IDO, PD-L1, MGMT, and Ki67 expression, which are signatures of a less aggressive tumor phenotype. These findings suggest that prolonged CBD exposure can precondition the tumor microenvironment toward an anti-tumor state, improving disease control and potentially lowering relapse risk.

This study introduces a novel concept of CBD pretreatment as an immune-modulatory strategy with high translational potential for glioblastoma management.”

https://pubmed.ncbi.nlm.nih.gov/41596406

“Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has attracted growing interest for its broad spectrum of therapeutic properties, including anti-cancer and neuroprotective effects [1,3]. Preclinical studies have demonstrated that CBD exerts anti-proliferative, pro-apoptotic, anti-inflammatory, and anti-angiogenic effects across various tumor models, including GBM.

Our previous work and other studies have shown that CBD can inhibit GBM growth in the brain by modulating the endocannabinoid system, promoting cell cycle arrest, and impairing angiogenesis “

“In this study, we investigate the prophylactic potential of chronic CBD administration via inhalation in a murine model of GBM.”

“This preclinical investigation demonstrates that prolonged inhaled CBD pretreatment significantly suppresses glioblastoma (GBM) progression in a murine model by targeting multiple hallmarks of tumor biology.”

“Collectively, these findings support the development of CBD as a non-invasive, prophylactic adjunct to standard GBM treatments and provide a strong rationale for further translational studies aimed at optimizing CBD-based interventions to improve clinical outcomes in this aggressive malignancy.”

https://www.mdpi.com/1422-0067/27/2/757


Cannabidiol Regulates CD47 Expression and Apoptosis in Jurkat Leukemic Cells Dependent upon VDAC-1 Oligomerization

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“Background: Cannabidiol (CBD) is a major non-psychoactive phytocannabinoid that exerts multiple biological effects in the body. It has been shown to exert anti-cancer effects in a variety of cancer cells, including acute lymphoblastic leukemia of pre-T cell origin (T-ALL), a highly aggressive hematological malignancy. However, the mechanisms underlying CBD’s anti-cancer effects are not fully understood. Furthermore, cancer cells abundantly express surface CD47, which is a negative regulator of phagocytosis and linked with cell survival/death. Little is known about CBD effects on the expression of CD47 in T-ALL cells. The objectives of this study were to address these issues. 

Methods: Studies were conducted in vitro using Jurkat cells and human peripheral blood mononuclear cells in different culture conditions, CBD concentrations, and in the presence or absence of different reagents. 

Results: CBD downregulates CD47 expression and induces apoptosis in Jurkat cells. Similar biological effects of CBD were also observed in primary human CD4+ T cells, albeit at reduced levels. The CBD’s effects on CD47 expression and apoptosis were not rescued by a cannabinoid receptor (CBR)-2 agonist, a CBR-2 antagonist, or an anion channel blocker. However, these effects on CD47 expression and apoptosis were significantly rescued by a Voltage-Dependent Anion Channel (VDAC)-1 oligomerization inhibitor. 

Conclusions: Overall, we conclude that CBD downregulates CD47 expression and induces apoptosis involving VDAC-1 oligomerization. Furthermore, they also suggest that CBD’s pro-apoptotic effects on primary human T cells should also be monitored if it is used as an anti-cancer adjuvant or neo-adjuvant therapeutic in cancer patients.”

https://pubmed.ncbi.nlm.nih.gov/41599693

“Cannabis has been used by humans for recreational, spiritual, and medicinal purposes for millennia.”

“In in vitro studies, CBD downregulates CD47 expression and induces apoptosis in Jurkat leukemic T cells.”

https://www.mdpi.com/1424-8247/19/1/95

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