Cannabis Extracts on Glioblastoma Cell Lines: Chemical Composition and Pharmacologic Insights

Glioblastoma multiforme (GBM), also called grade IV astrocytoma, is an aggressive, malignant brain tumor with a low treatment success rate, particularly in patients with immune checkpoint-active tumors. These types of tumors are associated with a 5-year survival rate of <3%. Targeted treatments specifically designed for GBM are urgently needed. The aim of this study was to evaluate the effects of chemovar-specific cannabis extractions (CSCEs) in patients with GBM using liquid chromatography-mass spectrometry (LC-MS).

FAAH inhibition ameliorates breast cancer in a murine model

Breast cancer is the leading cancer among females worldwide. Disease outcome depends on the hormonal status of the cancer and whether or not it is metastatic, but there is a need for more efficacious therapeutic strategies where first line treatment fails. In this study, Fatty Acid Amide Hydrolase (FAAH) inhibition and endocannabinoids were examined as therapeutic alternatives. FAAH is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive, and FAAH inhibition is predicted to increase cancer cell death. To test this, breast cancer cells were probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of the two treatments, and assessed for viability.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges

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.

2074P Oral cannabidiol for prevention of chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is experienced by 37–84% of patients during and/or after end-of-treatment and often results in discontinuation of anti-neoplastic treatment and impairment of health-related quality of life. Cannabidiol (CBD) has shown preventive effects in CIPN animal models without compromising chemotherapy efficacy.

Phytochemical characterization and cytotoxic potential of extracts from roots and inflorescences of Cannabis sativa L. cv. Eletta Campana

Cannabis roots have been used in folk medicine for millennia and as nutrient storage systems, contain compounds that may have medicinal value. Despite this, cannabis roots have generally received little attention compared to cannabis flowers, leaves and seeds and were for a long time considered just a waste product. In this paper, for the first time, the extracts of dried roots and in- florescences of Cannabis sativa L. cv Eletta Campana, were chemically investigated in order to compare their metabolite content. The obtained results highlighted a profile rich in fatty acids in the roots and cannabinoids in the inflorescences. Other components such as monoterpenes, sesquiterpenes, diterpenes and triterpenes were also detected. The extracts were also evaluated in terms of cytotoxic activity by using a panel of cancer cell lines derived from different histotypes including melanoma (A375, M14), colon (HCT116, HT29), breast (MDAMB231, MCF7) and non- small cell lung cancer (H1299, A549). Although both extracts significantly reduced the cancer cell viability, the inflorescence extract was more potent. Furthermore, the latter induced a comparable response in all tested cancer cell lines, while melanoma and non-small cell lung cancer were the most sensitive histotypes to the root extract treatment.

Cell death induction and intracellular vesicle formation in human colorectal cancer cells treated with Δ9 -Tetrahydrocannabinol

Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application. This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We inves-tigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells.

Anti-proliferative effect of Cannabidiol in Prostate cancer cell PC3 is mediated by apoptotic cell death, NFκB activation, increased oxidative stress, and lower reduced glutathione status

Prostate cancer is the second most frequent cancer diagnosed in men in the world today. Almost all prostate cancers are adenocarcinomas and develop from gland cells. We used the PC3 prostate cancer cell line, which is well studied and derived from a bone metastasis of a grade IV prostatic adenocarcinoma. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, is a cannabinoid with anti-tumor properties but its effects on prostate cancer cells are not studied in detail. Here, we found cannabidiol decreased prostate cancer cell (PC3) viability up to 37.25% and induced apoptotic cell death in a time and dose-dependent manner. We found that CBD activated the caspases 3/7 pathways and increased DNA fragmentation. Furthermore, we observed an increase of pro-apoptotic genes Bax, an increased level of reactive oxygen species, lower reduced glutathione level, and altered mitochondrial potential in response to CBD treatment leading to lower cellular ATP. Overall, our results suggest that CBD may be effective against prostate cancer cells.

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

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.

Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells

Prostate cancer is the fifth leading cause of cancer death in men, responsible for over 375,000 deaths in 2020. Novel therapeutic strategies are needed to improve outcomes. Cannabinoids, chemical components of the cannabis plant, are a possible solution. Preclinical evidence demonstrates that cannabinoids can modulate several cancer hallmarks of many tumor types. However, the therapeutic potential of cannabinoids in prostate cancer has not yet been fully explored. The aim of this study was to investigate the antiproliferative and anti-invasive properties of cannabidiol (CBD) in prostate cancer cells in vitro. CBD inhibited cell viability and proliferation, accompanied by reduced expression of key cell cycle proteins, specifically cyclin D3 and cyclin-dependent kinases CDK2, CDK4, and CDK1, and inhibition of AKT phosphorylation. The effects of CBD on cell viability were not blocked by cannabinoid receptor antagonists, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, or an agonist of the G-protein-coupled receptor GPR55, suggesting that CBD acts independently of these targets in prostate cancer cells. Furthermore, CBD reduced the invasiveness of highly metastatic PC-3 cells and increased protein expression of E-cadherin. The ability of CBD to inhibit prostate cancer cell proliferation and invasiveness suggests that CBD may have potential as a future chemotherapeutic agent.

The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions

Phytocannabinoids have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein beta amyloid (Aβ). We characterised the capacity of six phytocannabinoids: cannabichromene, cannabigerol, cannabinol, cannabidivarin, cannabidiol and Δ9-tetrahydrocannabinol, to disrupt Aβ aggregation and protect against Aβ-evoked neurotoxicity in PC12 cells. Neuroprotection against lipid peroxidation and Aβ-induced cytotoxicity was assessed using the MTT assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ aggregation and fluorescence microscopy, with morphometrics and principal component analysis to assess PC12 cell morphology.

Could cannabinoids provide a new hope for ovarian cancer patients?

It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these compounds as anti-cancer therapies in clinical practice as they do not produce the typical toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses.

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

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.