Prevention of Allodynia and Hyperalgesia by Cannabidiol in a Rat Model of Chemotherapy-Induced Peripheral Neuropathy

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“This study demonstrates the utility of a rat model of chemotherapy-induced peripheral neuropathy (CIPN) to assess the ability of the non-psychoactive cannabinoid cannabidiol (CBD) to modulate the development of this syndrome in vivo. The method utilizes the chemotherapeutic agent paclitaxel to generate an allodynic phenotype in the animals.

This study describes how to handle and solubilize CBD, administer the chemotherapeutic agent, assess mechanical and cold sensitivity, and apply high-speed videography to measure nocifensive behavior in animals.

Using the procedures outlined, the data support that CBD prevents the allodynic phenotype from developing in the treated animals. No difference was observed in the CBD-treated animals from day 0 (pre-paclitaxel baseline) to day 7 (post-sensitization) in mechanical or thermal sensitivity, while the vehicle-treated animals became significantly more sensitive.

This response to treatment is durable up to the latest time point where data were collected (7 weeks). The addition of high-speed videography allows for a more granular and unbiased assessment of this behavioral phenotype (e.g., classification of analgesia and anti-allodynia).

This demonstrates both the utility of this model for cannabinoid drug characterization and the potential role of CBD in mitigating neuropathic pain.”

https://pubmed.ncbi.nlm.nih.gov/40622941/

“Co-administration of CBD with paclitaxel prevents the development of chemotherapy-induced peripheral neuropathy in rats. This protocol describes cannabinoid handling, inducing an allodynic phenotype in rats via chemotherapeutic administration, assessing mechanical and thermal allodynia, and using high-speed videography to distinguish allodynia and hyperalgesia.”

https://app.jove.com/t/68079/prevention-allodynia-hyperalgesia-cannabidiol-rat-model-chemotherapy

Impact of minor cannabinoids on key pharmacological targets of estrogen receptor-positive breast cancer

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“Endocrine therapy for estrogen receptor-positive (ER+) breast cancer has significantly improved over the last decades. However, it presents some limitations that make the search for novel therapeutic options mandatory.

Several studies have been conducted to understand the anti-tumor potential of cannabinoids in breast cancer. Yet, most of them are focused on the major phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). However, Cannabis has other minor phytocannabinoids whose anti-cancer properties are still to be elucidated.

Here, we investigated the mechanisms of action of four minor cannabinoids, cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC), in 2D and 3D ER+ breast cancer models.

These cannabinoids dysregulate MCF-7aro cell cycle progression, induce apoptosis by different mechanisms, and inhibit the growth of MCF-7aro spheroids. CBG exerts its effects through a down-regulation of both ER and AR protein levels, while CBDV reduces aromatase protein levels. CBN and CBC simultaneously affect the three targets, ER, aromatase, and AR.

In fact, CBN and CBC present an AR-dependent cell death, down-regulate aromatase levels, and act as ER negative regulators impairing cancer cell growth. CBN caused the most pronounced effects.

Overall, this study highlights the anti-cancer properties and the therapeutic potential of these minor cannabinoids in ER+ breast cancer.”

https://pubmed.ncbi.nlm.nih.gov/40615070/

https://www.sciencedirect.com/science/article/pii/S1388198125000666?via%3Dihub

Neutrophil extracellular traps and cannabinoids: potential in cancer metastasis

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“Cancer is the second leading cause of global mortality after cardiovascular diseases, with breast, lung, colon, and prostate cancers being the most common. WHO projects around 30 million new cancer cases worldwide by 2045, with breast cancer being the most common in women and lung cancer in men.

Metastasis is responsible for nearly 90% of cancer-related deaths. Breast and lung cancers tend to metastasize to the bones, lymph nodes, lungs, liver, and brain. Lungs remains one of the most common organs to which various forms of cancer metastasize.

An important factor in metastasis is NETosis – it can initially help to eliminate cancer cells, but it can also promote metastasis. Phytocannabinoids, compounds derived from Cannabis sativa, and the endocannabinoid system (ECS) offer promising therapeutic potential to inhibit NETosis and consequently cancer development and metastasis.

Although the precise effects of phytocannabinoids on neutrophil functions and NETosis are not fully understood and require further research in the context of cancer, preliminary studies suggest their potential to inhibit NET release in various disease models.

This review consolidates current knowledge and provides new insights into how phytocannabinoids and the ECS may serve as effective therapeutic tools to limit cancer metastasis.”

https://pubmed.ncbi.nlm.nih.gov/40599866/

“Research indicates that metastatic progression is responsible for most deaths caused by breast cancer, with metastatic processes accounting for nearly 90% of cancer-related mortality.”

“Phytocannabinoids, together with the endocannabinoid system (ECS), represent a highly promising therapeutic avenue for attenuating neutrophil effector functions, particularly the process of NETosis.

We believe that these compounds have significant potential as agents capable of effectively inhibiting metastatic progression.

Phytocannabinoids, derived primarily from the Cannabis sativa plant, are a group of organic compounds that interact with the endocannabinoid system (ECS) in the human body.”

“Both phytocannabinoids and the endocannabinoid system (ECS) show significant therapeutic potential in cancer treatment. Research indicates that these agents affect the proliferation, apoptosis, migration, and invasiveness of cancer cells. In addition, they modulate the tumor microenvironment, particularly the cells of the immune system.”

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1595913/full

Cannabinoids as Potential Therapeutic Agents in the Treatment of Pancreatic Cancer

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“Pancreatic cancer is one of the most aggressive and lethal malignancies, with limited therapeutic options and low survival rates, primarily due to late-stage diagnosis and resistance to conventional therapies. Recently, cannabinoids have gained attention for their analgesic and antiemetic properties in cancer symptom management, as well as for their potential anticancer effects. This review explores the mechanisms by which cannabinoids may impact pancreatic cancer progression, focusing on their molecular interactions and therapeutic potential.”

https://pubmed.ncbi.nlm.nih.gov/40578954/

“Preclinical studies revealed that cannabinoids, primarily Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD), exert anti-tumor effects through mechanisms such as apoptosis induction, cell cycle arrest, inhibition of angiogenesis, immune modulation, and reduction of oxidative stress.”

“THC, the principal psychoactive cannabinoid, and CBD, a non-psychoactive counterpart, have both demonstrated pro-apoptotic properties in pancreatic cancer cells by inducing apoptosis”

“Studies have shown that THC and CBD can induce cell cycle arrest at the G0/G1 phase, limiting cancer cell division and tumor growth.”

“Taken together, these studies suggest that cannabinoids play anticancer roles in pancreatic cancer, and should be further studied for use as therapeutic agents in the treatment of pancreatic cancer.”

https://ar.iiarjournals.org/content/45/7/2719

Evaluating the Antitumor Potential of Cannabichromene, Cannabigerol, and Related Compounds from Cannabis sativa and Piper nigrum Against Malignant Glioma: An In Silico to In Vitro Approach

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“Malignant gliomas, including glioblastoma multiforme (GBM), are highly aggressive brain tumors with a poor prognosis and limited treatment options.

This study investigates the antitumor potential of bioactive compounds derived from Cannabis sativa and Piper nigrum using molecular docking, cell viability assays, and transcriptomic and expression analyses from public databases in humans and cell lines.

Cannabichromene (CBC), cannabigerol (CBG), cannabidiol (CBD), and Piper nigrum derivates exhibited strong binding affinities relative to glioblastoma-associated targets GPR55 and PINK1.

In vitro analyses demonstrated their cytotoxic effects on glioblastoma cell lines (U87MG, T98G, and CCF-STTG1), as well as on neuroblastoma (SH-SY5Y) and oligodendroglial (MO3.13) cell lines, revealing interactions among these compounds. The differential expression of GPR55 and PINK1 in tumor versus normal tissues further supports their potential as biomarkers and therapeutic targets.

These findings provide a basis for the development of novel therapies and suggest unexplored molecular pathways for the treatment of malignant glioma.”

https://pubmed.ncbi.nlm.nih.gov/40565152/

“While docking studies suggest strong interactions between Piper nigrum derivatives, cannabinoids, and targets such as PINK1 and GPR55, in vitro experiments confirmed the cytotoxic potential of these compounds in glioblastoma cell lines, with cannabinoids like CBG and CBD showing significant dose-dependent reductions in cell viability, comparable to established chemotherapeutic agents.”

https://www.mdpi.com/1422-0067/26/12/5688

Perceptions, Uses, and Information Sources of Medical Cannabis Among Patients With Cancer

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“Purpose: Although medical cannabis (MC) has been shown to relieve cancer- and treatment-related symptoms, there is increasing misinformation regarding its antitumor efficacy. We aimed to identify opportunities for oncologists to communicate evidence-based guidance to patients regarding its use.

Methods and materials: Patients with cancer seen in radiation oncology clinic between June 2022 and July 2023 were surveyed with a questionnaire regarding their perceptions and information sources of MC. Associations between survey responses and demographic and disease variables were evaluated. Qualitative thematic analysis was performed on narrative responses in search of common themes.

Results: Eighty-four patients (84% completion rate) were included in the analysis. Most (83.3%) strongly agreed or agreed that MC can provide symptom relief, whereas a subset of patients (15.5%) strongly agreed or agreed that MC can cure cancer. This latter subcohort was significantly more likely to identify as Hispanic/Latino (38.5% vs 9.9%, P = .009) and less likely to be up to date on COVID-19 vaccinations (30.8% vs 8.5%, P = 0.044). Identifying as Hispanic/Latino remained significantly associated with strongly agreeing or agreeing that MC can cure cancer on bivariate analysis (odds ratio, 6.528; 95% CI, 1.477-28.715; P = .012). Education level, other sociodemographic characteristics, and sources for information about MC were not significantly different between these patients. Thematic analysis revealed that patients hoped to learn more about MC from their oncologists but perceived them to be unknowledgeable on the subject.

Conclusions: Although most patients consider MC to be a valuable addition to conventional therapies for managing refractory symptoms, a subset believed it had potential as an anticancer therapy. Many patients rely on unregulated sources, highlighting the need for providers to address misinformation, bridge knowledge gaps, and clarify its use.”

https://pubmed.ncbi.nlm.nih.gov/40546850/

“Most patients (83.3%) strongly agreed or agreed that MC can provide symptom relief for cancer and treatment-related symptoms, whereas 15.5% strongly agreed or agreed that MC can cure cancer.”

https://www.advancesradonc.org/article/S2452-1094(24)00241-0/fulltext

Cannabidiol (CBD) as a potential therapeutic agent for liver cancer: a comprehensive review of current evidence

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“Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality with limited treatment options. Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown anticancer properties.

This review analyzes CBD’s therapeutic potential in HCC, focusing on mechanisms, preclinical/clinical findings, and integration into treatment strategies. A systematic search (PubMed, Scopus, Web of Science, Google Scholar) up to March 2025 identified 16 relevant studies (in vitro, in vivo, clinical).

CBD exerts antitumor effects via multiple pathways, including apoptosis, autophagy regulation, metastasis suppression, and tumor microenvironment modulation. CBD interacts with the endocannabinoid system (ECS), inhibits oncogenic signaling (PI3K/AKT/mTOR), and enhances chemotherapeutic efficacy (sorafenib, cabozantinib).

Studies show CBD induces pyroptosis via caspase-3/GSDME, and modulates autophagy by inhibiting the PI3K/Akt/mTOR pathway. It also sensitizes HCC cells to sorafenib and cabozantinib. Preclinical results are promising, but clinical studies are limited. Challenges like bioavailability and potential hepatotoxicity require investigation. Future research should optimize formulations, determine dosing, and conduct clinical trials to validate CBD’s efficacy/safety in HCC patients.

Validated CBD could offer an innovative HCC management option.”

https://pubmed.ncbi.nlm.nih.gov/40533744/

“Overall, while preclinical findings strongly support the therapeutic potential of CBD in HCC, robust clinical trials are urgently needed to confirm its efficacy, safety, optimal dosing strategies, and long-term effects. If validated, CBD could represent an innovative and complementary approach in the management of hepatocellular carcinoma.”

https://cancerci.biomedcentral.com/articles/10.1186/s12935-025-03870-3

Hemp-Derived Iron Oxide Nanoparticles for Biomedical Applications: Synthesis, Characterization, and Therapeutic Potential

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“Iron oxide nanoparticles (IONPs) have emerged as the most widely synthesized metal nanoparticles in sustainable chemistry due to their unique magnetic properties, excellent biocompatibility, biodegradability, and non-toxicity.

In this study, IONPs are successfully synthesized via a rapid, sustainable, and environmentally friendly green synthesis approach using Cannabis sativa L. leaf extract. X-ray diffraction analysis determined that the synthesized NPs had an average particle size of 18.8 nm, while transmission electron microscopy images reveal a spherical morphology with sizes ranging from 12 to 21 nm.

Fourier-transform infrared spectroscopy analysis confirmed the presence of cannabinoids, terpenoids, and flavonoids, which are believed to play a crucial role in the formation and stabilization of IONPs. Its photocatalytic potential is demonstrated through the degradation of bromophenol blue dye.

Additionally, the NPs exhibited significant antibacterial and antifungal activity against various microbial species, along with promising anticancer effects on cancer cell lines.

In conclusion, this study provides a promising foundation for advancing the large-scale, commercial production of IONPs through green synthesis methods. By offering an eco-friendly and efficient alternative to conventional nanoparticle synthesis, the findings contribute significantly to the growing body of research in sustainable nanotechnology.”

https://pubmed.ncbi.nlm.nih.gov/40525672/

“In this study, IONPs were successfully synthesized via a single-step green approach using C. sativa leaf extract as the sole reducing and stabilizing agent, eliminating the need for secondary chemicals. Collectively, these findings underscore the potential of eco-friendly IONPs for biomedical and environmental applications, aligning with sustainable nanotechnology paradigms.”

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/open.202500189

Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy

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“Background: Cancer remains a major global health issue, prompting the need for innovative treatment approaches that extend beyond conventional methods such as chemotherapy and radiation. The endocannabinoid system (ECS), primarily the cannabinoid receptors CB1R and CB2R, presents a promising opportunity for cancer therapy by selectively targeting cell signaling pathways. This systematic review intends to explore the mode of action of synthetic cannabinoids as potential anticancer agents and their impact on tumor growth in various cancer cell lines.

Methods: Of the 287 articles identified between January 1990 and July 2024, 27 studies met strict criteria focusing on their anticancer effects. Data extraction and quality assessment were conducted using GRADE criteria and the Cochrane Risk of Bias tool, ensuring robust evaluation of the studies’ reliability.

Results: Various pharmacological actions of synthetic cannabinoids function as agonists, antagonists, and inverse agonists at the CB1R and CB2R receptors. Key findings indicate that CB2R agonists significantly reduce cancer cell proliferation through diverse mechanisms, with selective CB2R agonists effectively inhibiting cancer cell growth and survival. Studies involving CB1R antagonists, particularly in conjunction with CB2R agonists, highlight their role in blocking CB1R to either validate or enhance the efficacy of CB2R agonists in mitigating tumor growth. Inverse agonists targeting CB2R have shown moderate success in inducing cancer cell death by disrupting survival pathways. Notably, synthetic cannabinoid agonists display significant potential in targeting CB1 and CB2 receptors to inhibit tumor proliferation and promote apoptosis across various cancer types.

Conclusion: The systematic review concludes that CB2R agonists can effectively inhibit tumor growth while inducing apoptosis in various cancers. Although CB1R agonists show potential in modulating cancer pathways, there is a notable lack of research on CB1 inverse agonists, emphasizing the need for further investigation. Additionally, the study advocates for greater exploration of mixed receptor agonist and receptor mode of action to validate these promising therapeutic approaches.”

https://pubmed.ncbi.nlm.nih.gov/40483537/

“Phytocannabinoids, which are the natural cannabinoids found in Cannabis sativa, have been extensively studied for their potential anticancer effects. These compounds act as agonists for cannabinoid receptor 1 and cannabinoid receptor 2, facilitating their therapeutic applications through the activation of these CBRs. By activating CB1R and CB2R, phytocannabinoids produce various therapeutic effects, including anti-nociception, anti-inflammation, anticonvulsant, and anti-emetic properties.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00289-5

CBD promotes antitumor activity by modulating tumor immune microenvironment in HPV associated head and neck squamous cell carcinoma

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“Introduction: Marijuana use is associated with HPV-positive head and neck squamous cell carcinoma (HNSCC). However, cannabinoid use continues to increase in the US general population for recreational purposes as well as in cancer patients for palliative care. In this study, we explored the role of cannabidiol (CBD) in promoting anti-tumor activity by modulating immune response in HPV-positive HNSCC by using pre-clinical models.

Methods: The anti-proliferative effect of CBD on HPV-positive HNSCC cells was evaluated through BrdU, apoptosis and migration analyses, followed by western blot analysis to assess its role in activating the MAPK pathway. Next, the anti-tumor immune response of CBD was evaluated in immunocompetent syngeneic mouse as well as in immune-deficient B6.129S7-Rag1tm1Mom/J or Rag 1 Knockout mice (Rag1 -/-) and athymic nude mouse. Immune cell infiltration was measured by flow cytometry, IHC and multiplex IHC analysis after subcutaneous injection of mEER cells. Furthermore, the anti-tumor activity of CBD on the tumor microenvironment was evaluated after the depletion of CD4+T cells and CD8+T cells in murine models.

Results: We observed CBD treatment inhibited cell proliferation and migration by promoting apoptosis in HPV-positive HNSCC cells through activation of the MAPK pathway and its associated markers like ERK1/2, JNK/SAPK and MK2. CBD significantly inhibited tumor growth in immunocompetent mice but had no effect in immune-deficient models, indicating an immune-dependent mechanism. CBD enhanced infiltration of CD4+T and CD8+T cells, CD19+B cells, NK cells, and M1-like macrophages into the primary tumors of immunocompetent syngeneic mice models, implicating an enhanced anti-tumor immune response. Interestingly, we observed a significant increase in tumor volume in CD4-depleted mice treated with CBD as compared to CBD-treated wild-type mice suggesting the importance of CD4+T cells in CBD-mediated anti-tumor activity. Finally, multiplex IHC analysis demonstrated co-localization of CD4+T and CD8+ T cells with the activated MAPK marker phospho-p38 in CBD-treated tumors.

Discussion: CBD inhibits tumor cell proliferation in HPV-positive HNSCC by activating the MAPK pathway. It also enhances anti-tumor activity by modulating the tumor immune microenvironment, promoting co-localization of p38 MAPK-activated CD4+ and CD8+ T cells.”

https://pubmed.ncbi.nlm.nih.gov/40475776/

“In conclusion, our study suggests that CBD inhibits tumor cell proliferation in HPV-positive HNSCC by activating MAPK pathway and exhibits anti-tumor activity by modulating the CD4+T and CD8+T cells in the tumor immune microenvironment. Therefore, CBD may potentially provide a supportive role in cancer therapy through immune-mediated mechanisms.”

“As such, specific cannabinoids may become an integral component of comprehensive cancer treatment regimens, offering new hope to patients with HPV-positive head and neck cancer.”

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1528520/full