CBD as a Physiological Modulator for Cancer

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The current standard-of-care treatment regimens for cancer frequently have serious and irreversible adverse effects. Ideally, therapeutic modalities should help control symptoms and improve the patient’s quality of life while causing minimal or no toxic effects. In this regard, it is worth examining cannabidiol (CBD) for its potential anticancer properties. CBD may possess antitumor activity through several mechanisms, including regulating reactive oxygen species, endoplasmic reticulum stress, inflammation, and immune modulation. In addition, pre-clinical studies indicate that CBD is a potential modulator of growth factors and induces apoptosis in tumor cells. This review summarizes the evidence regarding the effects of CBD as a non-toxic adjuvant in cancer care.

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Disorders of cancer metabolism: The therapeutic potential of cannabinoids

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Abnormal energy metabolism, as one of the important hallmarks of cancer, was induced by multiple carcinogenic factors and tumor-specific microenvironments. It comprises aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis. Considering that metabolic reprogramming provides various nutrients for tumor survival and development, it has been considered a potential target for cancer therapy. Cannabinoids have been shown to exhibit a variety of anticancer activities by unclear mechanisms. This paper first reviews the recent progress of related signaling pathways (reactive oxygen species (ROS), AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), hypoxia-inducible factor-1alpha (HIF-1α), and p53) mediating the reprogramming of cancer metabolism (including glucose metabolism, lipid metabolism, and amino acid metabolism). Then we comprehensively explore the latest discoveries and possible mechanisms of the anticancer effects of cannabinoids through the regulation of the above-mentioned related signaling pathways, to provide new targets and insights for cancer prevention and treatment.

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Legislative and Administrative Guidelines for Regulating Cannabis Use in Introduction Healthcare Facilities

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In 2018, Ryan Bartell, a 41-y/o Coast Guard Veteran with end-stage pancreatic cancer, was admitted for 24- hour hospice care at MarinHealth Medical Center in Greenbrae, California. Due to chronic, unrelenting pain, Bartell was heavily sedated with opioids and unable to communicate with family, friends, and/or caretakers. Because of the opioid-related cognitive impairment, Ryan’s father requested that Bartell be allowed to use medical cannabis to lessen his need for opioids and allow increased interaction with his family during his final days. Doctors claimed that the use of medicinal cannabis would threaten the hospital’s federal funding (due to the federal prohibition of cannabis) and therefore refused to allow its use [1]. Bartell’s family had him transferred to a hospital in Washington State that allowed the use of medical cannabis. After using cannabis, Bartell was able to cease the use of opioids, remain comfortable, and communicate with his loved ones in his final days.

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Cannabis use in cancer patients: acute and sustained associations with pain, cognition, and quality of life

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Given the myriad of negative sequalae associated with cancer and its treatment, the palliative use of cannabis by cancer patients is increasingly of special interest. This research sought to explore associations of acute and sustained use of legal market edible cannabis products on pain, cognition, and quality of life in a group of cancer patients. In this observational study, cancer patients completed a baseline appointment, a two-week ad libitum cannabis use period, and an acute administration appointment that included assessments before cannabis use, one-hour post-use, and two-hour post-use. Participants completed self-report questionnaires related to the primary outcomes and the Stroop task as a measure of objective cognitive function.

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Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis

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Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.

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Gene Profiling of Cannabis-sativa-mediated Apoptosis in Human Melanoma Cells

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Malignant melanoma is an aggressive skin cancer, accounting for the majority of skin cancer deaths. Prognosis is often poor and finding effective treatment remains a challenge. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are main bioactive components of Cannabis sativa plant extracts that have been shown to exert anti-tumor effects. In this study, we aimed to perform gene expression analysis of human melanoma A375 cells following stimulation with C. sativa extracts.

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Phytocannabinoids in Triple Negative Breast Cancer Treatment: Current Knowledge and Future Insights

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Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, which is deficient in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Thus, TNBC cells are unable to respond to the conventional hormonal therapies, making chemotherapy the only therapeutic choice. Patients with TNBC develop metastasis and recurrence over time and have reduced survival compared to patients with other subtypes of breast cancer. Therefore, there is a need for innovative therapies. Data emerged from pre-clinical studies, highlighted various antitumor activities of plant-derived Cannabis sativa and synthetic cannabinoids (CBs), including delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). On the contrary, some studies indicated that CBs might also promote tumor progression. At present, clinical studies on the effects of CBs from Cannabis sativa in cancer patients are few. In the present study, we reviewed known and possible interactions between cannabinoids and TNBC therapies.

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Locally advanced HPV-positive oropharyngeal cancer cured with single agent pembrolizumab in a patient using cannabis: a case report

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The success of smoking cessation programs is inarguable and has saved thousands of lives by decreasing the incidence of deadly malignancies, including head and neck cancer. Meanwhile, we are witnessing an increasing incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), especially in a population of older Caucasian males. Approval and use of immune checkpoint inhibitors (ICI), such as pembrolizumab, have resulted in improved outcomes in patients with HPV-induced OPSCC. It is successfully used in the treatment of recurrent and metastatic disease with meaningful improvements in overall survival. However, concurrent chemoradiotherapy (CCRT) remains the conventional first-line treatment of locally advanced disease in eligible patients and is associated with substantial morbidity.

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Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment

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It is easy to find success stories on the internet of patients with cancer who seem to benefit from using cannabis products. However, scientific substantiation is usually lacking. Therefore, there are critical questions among clinicians and other healthcare providers about the potential of cannabis products in cancer care. In this article, we aim to give direction for making choices about the responsible use of cannabis products in oncology by addressing the following questions: How does cannabis work? What is medicinal cannabis? What kind of cannabis products are in use? What is their legal status? Is there evidence for therapeutic effects in patients with cancer? What is the risk–benefit balance in terms of adverse effects, (potential) drug interactions, symptom management and antitumour activity? May cannabis products provide added value in the treatment of patients with cancer? We end up with an outlook and perspective determining the place of cannabis products in oncology.

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Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer

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In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood. Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signaling. Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signaling pathways. The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.

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Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation

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Globally, it is evident that glioblastoma multiforme (GBM) is an aggressive malignant cancer with a high mortality rate and no effective treatment options. Glioblastoma is classified as the stage-four progression of a glioma tumor, and its diagnosis results in a shortened life expectancy. Treatment options for GBM include chemotherapy, immunotherapy, surgical intervention, and conventional pharmacotherapy; however, at best, they extend the patient’s life by a maximum of 5 years. GBMs are considered incurable due to their high recurrence rate, despite various aggressive therapeutic approaches which can have many serious adverse effects. Ceramides, classified as endocannabinoids, offer a promising novel therapeutic approach for GBM. Endocannabinoids may enhance the apoptosis of GBM cells but have no effect on normal healthy neural cells.

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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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