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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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Toxicity of Cannabigerol: Examination of Long-Term Toxicity and Lifespan in Caenorhabditis elegans and 14-Day Study in Sprague Dawley Rats

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Cannabigerol (CBG) is becoming widely available despite little being known about its potential toxicity or long-term effects. The present investigation involved two distinct studies. The first study explored acute and long-term effects of CBG on toxicity, lifespan, and aging in adult Caenorhabditis elegans (C. elegans). Animals were treated with CBG (0.075 lM–3.75 mM) to determine acute toxicity, mortality, and motility. Acute heat- induced stress survival (thermotolerance; 37°C for 4 h) following CBG administration (0.075–3.75 mM) was measured. Long-term toxicity of lifelong CBG administration (7.5, 75, or 375 lM CBG) was determined through changes in motility and lifespan duration. In the second study, healthy, adult, Sprague Dawley rats received 0, 35, 70, or 140 mg/kg-bw/day CBG (n = 5 per sex per group) daily for 14 days via oral gavage. Signs of gross toxicity and changes in behavior, body weight, food consumption, and serum chemistry were monitored. Liver, kidney, and adrenal gland weights were recorded, and histopathology of select tissues was examined.

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