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Effects of concomitant use of THC and irinotecan on tumour growth and biochemical markers in a syngeneic mouse model of colon cancer

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Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ9-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan’s systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.

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Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

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During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects.

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Cannabinoids and the endocannabinoid system in immunotherapy: helpful or harmful?

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Numerous studies in various cancer models have demonstrated that ingredients of cannabis can influence tumor growth through the endocannabinoid system (ECS), a network of molecules (mediators, receptors, transporters, enzymes) that maintains homeostasis and protection in many tissues. The main constituents of the ECS are the classical cannabinoid (CB) receptors, such as CB1 and CB2, their endogenous ligands (endocannabinoids), and the endocannabinoids’ synthesizing and degrading enzymes. The role of the ECS in cancer is still unclear and its effects often depend on the tumor entity and the expression levels of CB receptors. Many studies have highlighted the tumor cell-killing potential of CB1 agonists. However, cannabis is also known as an immunosuppressant and some data suggest that the use of cannabis during immunotherapy worsens treatment outcomes in cancer patients.

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Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

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Physicians’ ability to guide their patients on the use of medical cannabis can vary widely and is often shaped by their training, experiences, and the regulations and policies of their state. The goal of this qualitative study is to understand how prepared physicians are to certify and advise their patients to use medical cannabis. A secondary goal is to explore how physicians integrate certification into their clinical practices, and what factors shape their decisions and behaviors around certification.Using semi-structured interviews with 24 physicians authorized to certify patients to use medical cannabis in Pennsylvania, a state with a medical access only program, we explored how physi- cians are trained and set up their practices. Interviews were analyzed using a blend of directed and conventional, and summative content analysis.

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The Anti-Tumorigenic Role of Cannabinoid Receptor 2 in Colon Cancer: A Study in Mice and Humans

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The endocannabinoid system, particularly cannabinoid receptor 2 (CB2 in mice and CNR2 in humans), has controversial pathophysiological implications in colon cancer. Here, we investigate the role of CB2 in potentiating the immune response in colon cancer in mice and determine the influence of CNR2 variants in humans. Comparing wild-type (WT) mice to CB2 knockout (CB2−/−) mice, we performed a spontaneous cancer study in aging mice and subsequently used the AOM/DSS model of colitis-associated colorectal cancer and a model for hereditary colon cancer (ApcMin/+). Additionally, we analyzed genomic data in a large human population to determine the relationship between CNR2 variants and colon cancer incidence. Aging CB2−/− mice exhibited a higher incidence of spontaneous precancerous lesions in the colon compared to WT controls.

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Endocannabinoid signaling in glioma

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High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling path- ways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvi- ronment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.

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Cannabis Consumption Used by Cancer Patients during Immunotherapy Correlates with Poor Clinical Outcome

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Authors: Gil Bar-Sela, Cohen Idan, Salvatore Campisi-Pinto, Gil M Lewitus Published in Cancers August 2020 Abstract Cannabis or its derivatives are widely used by patients with cancer to help with…

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