“The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia.
Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.”
“Pain is a debilitating phenomenon that dramatically impairs the quality of life of patients. Many chronic conditions, including cancer, are associated with chronic pain. Despite pharmacological efforts that have been conducted, many patients suffering from cancer pain remain without treatment. To date, opioids are considered the preferred therapeutic choice for cancer-related pain management.
Unfortunately, opioid treatment causes side effects and inefficiently relieves patients from pain, therefore alternative therapies have been considered, including Cannabis Sativa and cannabinoids.
Accumulating evidence has highlighted that an increasing number of patients are choosing to use cannabis and cannabinoids for the management of their soothing and non-palliative cancer pain and other cancer-related symptoms. However, their clinical application must be supported by convincing and reproducible clinical trials.
In this review, we provide an update on cannabinoid use for cancer pain management. Moreover, we tried to turn a light on the potential use of cannabis as a possible therapeutic option for cancer-related pain relief.”
“Methotrexate (MTX) is a widely used medication for various cancers, yet its use is associated with adverse effects on organs, notably the lungs.
Cannabidiol (CBD), known for its antioxidant and anti-inflammatory properties, was investigated for its potential protective effects against MTX-induced lung injury.
Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (single 20 mg/kg intraperitoneal dose), MTX + CBD (single 20 mg/kg MTX with 0.1 ml of 5 mg/kg CBD for 7 days intraperitoneally) and CBD only (for 7 days). Lung tissues were analysed using histopathological, immunohistochemical and PCR methods after the study. Histopathological assessment of the MTX group revealed lung lesions like hyperemia, edema, inflammatory cell infiltration and epithelial cell loss. Immunohistochemical examination showed significant increases in Cas-3, tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB) expressions. PCR analysis indicated elevated expressions of apoptotic peptidase activating factor 1 (Apaf 1), glucose-regulated protein 78 (GRP 78), CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome C (Cyt C), along with reduced B-cell lymphoma-2 (BCL 2) expressions in the MTX group, though not statistically significant.
Remarkably, CBD treatment reversed these findings.
This study highlights CBD’s potential in mitigating MTX-induced lung damage, suggesting its therapeutic promise.”
“The findings from this study underscore the remarkable effectiveness of CBD in preventing histopathological damage within the lungs induced by MTX. The marked reduction observed in hyperemia, edema and infiltration, coupled with its notable reparative effects on epithelial loss, highlights the multifaceted benefits of CBD in mitigating pulmonary issues of MTX. Importantly, the statistical analysis revealed a significant improvement across all histopathological scoring parameters (p < 0.001). This reinforces the potential of CBD as a promising therapeutic agent for MTX-induced lung lesions and warrants further exploration in clinical settings. This study has demonstrated for the first time the reparative effects of CBD on the pathological findings induced by MTX in the lungs. There is now a need for novel and comprehensive research on the therapeutic utilization of CBD for this purpose.”
“Cancer and chemotherapy can both cause cachexia, a complex multi-organ syndrome characterized by body weight loss, due to adipose tissue and skeletal muscle wasting. Changes in body weight and muscle mass are predictive of response to chemotherapy, incidence of treatment-related complications and, ultimately, patient survival, but there are currently still no clear therapeutic strategies to counteract cachexia.
Cannabidiol (CBD) is a bioactive phytocannabinoid produced from a plant named Cannabis sativa. In recent years, CBD has demonstrated beneficial effects on maintaining skeletal muscle mass, function and metabolism in models of muscular dystrophy or diet-induced obesity.
Here, we used a model of myotubes in culture to evaluate the potential beneficial effects of CBD on cisplatin-induced skeletal muscle wasting. 24-h cisplatin treatment resulted in a ≈30% reduction in myotube diameter, driven by a drastic reduction in protein synthesis rate and a twofold increase in proteolysis. 24-h cisplatin treatment also significantly increased myotube TBARS content, catalase activity and antioxidant system mRNA levels (GPX1, SOD1, SOD2 and CAT) indicating increased oxidative stress. 24-h cisplatin treatment also increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4 and VDAC1, which are involved in mitochondrial respiration and control of apoptosis.
Importantly, CBD was found to antagonize chemotherapy-induced C2C12 myotube atrophy by promoting protein homeostasis and reducing oxidative stress. Our results show that CBD could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.”
“Pancreatic ductal adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis associated with this cancer is due to the absence of specific biomarkers, aggressiveness, and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that result in cancer-causing versions of the KRAS gene.
Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory properties.
Regarding the anticancer effect of CBG, up to now, there is only limited evidence in human cancers. To fill this gap, we investigated the effects of CBG on the PDAC cell lines, PANC-1 and MIAPaCa-2. The effect of CBG activity on cell viability, cell death, and EGFR-RAS-associated signaling was investigated. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate the effect of CBG on PDAC cell line viabilities. Annexin-V and Acridine orange staining, followed by cytofluorimetric analysis and Western blotting, were used to evaluate CBG’s effect on cell death. The modulation of EGFR-RAS-associated pathways was determined by Western blot analysis and a Milliplex multiplex assay. Moreover, by employing the MTT data and SynergyFinder Plus software analysis, the effect of the combination of CBG and chemotherapeutic drugs was determined.”
“In conclusion, our results showed that CBG, a non-psychomimetic cannabinoid from Cannabis Sativa L., can induce an anticancer effect in two human PDAC cell lines, supporting the ability of cannabinoids to interfere with several pro-tumoral pathways.”
“Mitogen-activated protein kinase (MAPK) activation by natural compounds is known to be involved in the induction of apoptosis, paraptosis, and autophagy.
Cannabidiol (CBD), a bioactive compound found in Cannabis sativa, is endowed with many pharmacological activities. We investigated the cytotoxic effect of CBD in a panel of colorectal cancer (CRC) cells (HT-29, SW480, HCT-116, and HCT-15).
CBD induced significant cytotoxicity as evidenced by the results of MTT assay, live-dead assay, and flow cytometric analysis. Since CBD displayed cytotoxicity against CRC cells, we examined the effect of CBD on apoptosis, paraptosis, and autophagy. CBD decreased the expression of antiapoptotic proteins and increased the Annexin-V-positive as well as TUNEL-positive cells suggesting that CBD induces apoptosis. CBD increased the expression of ATF4 (activating transcription factor 4) and CHOP (CCAAT/enhancer-binding protein homologous protein), elevated endoplasmic reticulum stress, and enhanced reactive oxygen species levels indicating that CBD also promotes paraptosis. CBD also induced the expression of Atg7, phospho-Beclin-1, and LC3 suggesting that CBD also accelerates autophagy.
Since, the MAPK pathway is a common cascade that is involved in the regulation of apoptosis, paraptosis, and autophagy, we investigated the effect of CBD on the activation of JNK, p38, and ERK pathways. CBD activated all the forms of MAPK proteins and pharmacological inhibition of these proteins reverted the observed effects.
Our findings implied that CBD could induce CRC cell death by activating apoptosis, paraptosis, and autophagy through the activation of the MAPK pathway.”
“The highly aggressive and invasive glioblastoma (GBM) tumour is the most malignant lesion among adult-type diffuse gliomas, representing the most common primary brain tumour in the neuro-oncology practice of adults. With a poor overall prognosis and strong resistance to treatment, this nervous system tumour requires new innovative treatment. GBM is a polymorphic tumour consisting of an array of stromal cells and various malignant cells contributing to tumour initiation, progression, and treatment response.
Cannabinoids possess anti-cancer potencies against glioma cell lines and in animal models.
To improve existing treatment, cannabinoids as functionalised ligands on nanocarriers were investigated as potential anti-cancer agents. The GBM tumour microenvironment is a multifaceted system consisting of resident or recruited immune cells, extracellular matrix components, tissue-resident cells, and soluble factors. The immune microenvironment accounts for a substantial volume of GBM tumours. The barriers to the treatment of glioblastoma with cannabinoids, such as crossing the blood-brain barrier and psychoactive and off-target side effects, can be alleviated with the use of nanocarrier drug delivery systems and functionalised ligands for improved specificity and targeting of pharmacological receptors and anti-cancer signalling pathways.
This review has shown the presence of endocannabinoid receptors in the tumour microenvironment, which can be used as a potential unique target for specific drug delivery. Existing cannabinoid agents, studied previously, show anti-cancer potencies via signalling pathways associated with the hallmarks of cancer. The results of the review can be used to provide guidance in the design of future drug therapy for glioblastoma tumours.”
“Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells.
Our recent study highlighted the remarkable in vitro anticancer effects of PHEC-66, an extract from Cannabis sativa, on the MM418-C1, MM329, and MM96L melanoma cell lines. However, the complete molecular mechanism behind this action remains to be elucidated.
This study aims to unravel how PHEC-66 brings about its antiproliferative impact on these cell lines, utilising diverse techniques such as real-time polymerase chain reaction (qPCR), assays to assess the inhibition of CB1 and CB2 receptors, measurement of reactive oxygen species (ROS), apoptosis assays, and fluorescence-activated cell sorting (FACS) for apoptosis and cell cycle analysis.
The outcomes obtained from this study suggest that PHEC-66 triggers apoptosis in these melanoma cell lines by increasing the expression of pro-apoptotic markers (BAX mRNA) while concurrently reducing the expression of anti-apoptotic markers (Bcl-2 mRNA). Additionally, PHEC-66 induces DNA fragmentation, halting cell progression at the G1 cell cycle checkpoint and substantially elevating intracellular ROS levels.
These findings imply that PHEC-66 might have potential as an adjuvant therapy in the treatment of malignant melanoma. However, it is essential to conduct further preclinical investigations to delve deeper into its potential and efficacy.”
“Introduction:Cannabis sativa is utilized mainly for palliative care worldwide. Ovarian cancer (OC) is a lethal gynecologic cancer. A particular cannabis extract fraction (‘F7’) and the Poly(ADP-Ribose) Polymerase 1 (PARP1) inhibitor niraparib act synergistically to promote OC cell apoptosis. Here we identified genetic pathways that are altered by the synergistic treatment in OC cell lines Caov3 and OVCAR3.
Materials and methods: Gene expression profiles were determined by RNA sequencing and quantitative PCR. Microscopy was used to determine actin arrangement, a scratch assay to determine cell migration and flow cytometry to determine apoptosis, cell cycle and aldehyde dehydrogenase (ALDH) activity. Western blotting was used to determine protein levels.
Results: Gene expression results suggested variations in gene expression between the two cell lines examined. Multiple genetic pathways, including Hippo/Wnt, TGF-β/Activin and MAPK were enriched with genes differentially expressed by niraparib and/or F7 treatments in both cell lines. Niraparib + F7 treatment led to cell cycle arrest and endoplasmic reticulum (ER) stress, inhibited cell migration, reduced the % of ALDH positive cells in the population and enhanced PARP1 cleavage.
Conclusion: The synergistic effect of the niraparib + F7 may result from the treatment affecting multiple genetic pathways involving cell death and reducing mesenchymal characteristics.”
“Cannabis sativa is utilized worldwide for palliative care and to alleviate various symptoms associated with medical conditions. Several dozen compounds are biosynthesized in the female inflorescence of each C. sativa strain. In total, around 600 different molecules can be found in cannabis, among them around 150 phytocannabinoids and hundreds of flavonoids and terpenes
Multiple studies suggest that phytocannabinoids have anti-cancer properties.
They inhibit several different features associated with cancer cells and tumors, including inhibiting cell proliferation and migration, inducing cell death, reducing angiogenesis, and inhibiting cancer cells’ invasiveness. This was demonstrated in several different cancer types, including cancers of the skin, lung, breast, prostate, and brain.
The best-studied anti-cancer activity is that of the most common phytocannabinoids cannabidiol (CBD) and Δ9–tetrahydrocannabinol (THC), and related synthetic compounds (e.g., HU-210 and WIN-55 212-2).
Phytocannabinoids have been found to affect cancer cells and tumors via several different genetic pathways and molecular mechanisms. For example, several signal transduction pathways can be activated by phytocannabinoids to induce cancer cell death, including cell cycle arrest, endoplasmic reticulum (ER) stress, oxidative stress, autophagy and/or apoptosis.”
“Objectives: To descriptively assess cannabis perceptions and patterns of use among older adult cancer survivors in a state without a legal cannabis marketplace.
Methods: This study used weighted prevalence estimates to cross-sectionally describe cannabis perceptions and patterns of use among older (65+) adults (N = 524) in a National Cancer Institute-designated center in a state without legal cannabis access.
Results: Half (46%) had ever used cannabis (18% following diagnosis and 10% currently). Only 8% had discussed cannabis with their provider. For those using post-diagnosis, the most common reason was for pain (44%), followed by insomnia (43%), with smoking being the most common (40%) mode of use. Few (<3%) reported that cannabis had worsened any of their symptoms.
Discussion: Even within a state without a legal cannabis marketplace, older cancer survivors might commonly use cannabis to alleviate health concerns but unlikely to discuss this with their providers.”
