“The endocannabinoid system has emerged as a considerable target for the treatment of diverse diseases.
In addition to the well-established palliative effects of cannabinoids in cancer therapy, phytocannabinoids, synthetic cannabinoid compounds as well as inhibitors of endocannabinoid degradation have attracted attention as possible systemic anticancer drugs.
As a matter of fact, accumulating data from preclinical studies suggest cannabinoids elicit effects on different levels of cancer progression, comprising inhibition of proliferation, neovascularisation, invasion and chemoresistance, induction of apoptosis and autophagy as well as enhancement of tumour immune surveillance.
Although the clinical use of cannabinoid receptor ligands is limited by their psychoactivity, nonpsychoactive compounds, such as cannabidiol, have gained attention due to preclinically established anticancer properties and a favourable risk-to-benefit profile.
Thus, cannabinoids may complement the currently used collection of chemotherapeutics, as a broadly diversified option for cancer treatment, while counteracting some of their severe side effects.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“During the last few decades, a large body of evidence has accumulated to suggest endocannabinoids, phytocannabinoids and synthetic cannabinoids exert an inhibitory effect on cancer growth via blockade of cell proliferation and induction of apoptosis. Some studies support the hypothesis that cannabinoids may enhance immune responses against the progressive growth and spread of tumours.” https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14426#bph14426-fig-0001
“Previous research has shown that cannabinoids can help lessen side effects of anti-cancer therapies. Now a new British Journal of Pharmacology review has examined their potential for the direct treatment of cancer. Studies have shown that cannabinoids may stop cancer cells from dividing and invading normal tissue, and they may block the blood supply to tumors. Some studies also indicate that cannabinoids may enhance the body’s immune response against the growth and spread of tumors.” https://www.eurasiareview.com/19072018-cannabinoids-may-have-a-vast-array-of-anti-cancer-effects/
“Cannabis ‘can act as a treatment for cancer’. Cannabis can enhance the immune system and act as a treatment for cancer, claims a new study. Scientists at Rostock University Medical Centre in Germany claimed the benefits following a review of more than 100 studies.” https://www.thelondoneconomic.com/news/cannabis-can-act-as-a-treatment-for-cancer/19/07/
“Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months.
The development of new therapeutic strategies for the management of gliomas is therefore essential.
Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture.
Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in immune-deficient mice.
Moreover, cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts.
A pilot clinical trial on patients with glioblastoma multiforme demonstrated their good safety profile together and remarkable antitumor effects, and may set the basis for further studies aimed at better evaluating the potential anticancer activity of cannabinoids.”
“Gliobalstoma multiforme (GBM) or grade 4 astrocytoma is the most malignant form of primary brain tumor. Treatment of glioblastoma is difficult despite of surgery, radiotherapy and chemotherapy. Patients with glioblastoma survive for less than 12 months.
Considering to biology function of glioblastoma, researchers have recently offered new therapeutic approaches such as cannabinoid therapy for glioblastoma.
Cannabinoids are active compounds of Cannabis sativa that operate in the body similar to endogenous canabinoids –the endocannabinoids- through cell surface receptors.
It is interesting that cannabinoids could exert a wide spectrum from antiproliferative effects in condition of the cell culture, animal models of glioblastoma and clinical trials.
As a result, Cannabinoids seem to modulate intracellular signaling pathways and the endoplasmic reticulum stress response in glioma cells.
Those play antitumoral effects through apoptosis induction and inhibition of glioblastoma angiogenesis.
The goal of this study was to discuss cannabinoid therapy and also what cellular mechanisms are involved in the tumoricidal effect of the cannabinoids.
In this review article, we will focus on cannabinoids, their receptor dependent functional roles against glioblastoma acccording to growth, angiogenesis, metastasis, and future purposes in exploring new possible therapeutic opportunities.”
http://journals.sbmu.ac.ir/Neuroscience/article/view/13655]]>
“Glioblastoma (GBM) is the most malignant brain tumor and one of the deadliest types of solid cancer overall. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection and radio-chemotherapy, more than 95% of GBM patients die within 5 years after diagnosis. Thus, there is still an urgent need to develop novel therapeutic strategies against this disease.
Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM.
This review article summarizes the latest findings on the molecular effects of cannabinoids on GBM, both in vitro and in (pre-) clinical studies in animal models and patients.
The therapeutic effect of cannabinoids is based on reduction of tumor growth via inhibition of tumor proliferation and angiogenesis but also via induction of tumor cell death. Additionally, cannabinoids were shown to inhibit the invasiveness and the stem cell-like properties of GBM tumors. Recent phase II clinical trials indicated positive results regarding the survival of GBM patients upon cannabinoid treatment.
Apart from a direct killing effect on tumor cells, cannabinoids can also induce cell cycle arrest thereby inhibiting tumor cell proliferation.
In conclusion, cannabinoids show promising anti-neoplastic functions in GBM by targeting multiple cancer hallmarks such as resistance to programmed cell death, neoangiogenesis, tissue invasion or stem cell-induced replicative immortality.
The effects of cannabinoids can be potentially enhanced by combination of different cannabinoids with each other or with chemotherapeutic agents. This requires, however, a detailed understanding of cannabinoid-induced molecular mechanisms and pharmacological effects.
Ultimately, these findings might foster the development of improved therapeutic strategies against GBM and, perhaps, other diseases of the nervous system as well.”
https://www.frontiersin.org/articles/10.3389/fnmol.2018.00159/full
“Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM.” https://www.ncbi.nlm.nih.gov/pubmed/29867351]]>
“In the last decades, the endocannabinoid system has attracted a great interest in medicine and cancer disease is probably one of its most promising therapeutic areas.
On the one hand, endocannabinoid system expression has been found altered in numerous types of tumours compared to healthy tissue, and this aberrant expression has been related to cancer prognosis and disease outcome, suggesting a role of this system in tumour growth and progression that depends on cancer type.
On the other hand, it has been reported that cannabinoids exert an anticancer activity by inhibiting the proliferation, migration and/or invasion of cancer cells; and also tumour angiogenesis.
The endocannabinoid system may be considered as a new therapeutic target, although further studies to fully establish the effect of cannabinoids on tumour progression remain necessary.”
https://www.ncbi.nlm.nih.gov/pubmed/29663308
“Anticancer Effects of Cannabinoids may be able to Prolong Life.
Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC.
Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive.
Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today’s scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.
THC, a partial CB1, CB2 agonist, has the stigma of psychotropic effects that are mediated by CB1 stimulation. However, CB1 stimulation is necessary for improving mood and appetite and many other effects. At present, it is hard to imagine a better approach than adjusting THC doses individually to balance wanted versus unwanted effects. Generally, higher doses are needed to achieve analgesic and antiemetic effects. Even much higher, supraphysiologic oral doses would be needed to combat tumors.
Combinations were synergistic under many circumstances such as in pain and antitumor studies. Cannabinoids differ in their antitumor activities and probably in their mechanisms and targets, which is a rationale for combinations. However, for many pharmacological effects (except against tumors) roughly 10-times higher daily doses are needed for CBD compared to THC.
In summary, the endocannabinoid system is likely playing a crucial role in palliative care. The future will show whether an optimized treatment strategy with cannabinoids can also prolong life of brain tumor patients by their virtue to combat cancer cells.”
“Funded by the National Institutes of Health to find evidence that marijuana damages the immune system, the study found instead that THC slowed the growth of 3 kinds of cancer in mice—lung and breast cancer, and a virus-induced leukemia. The US Drug Enforcement Agency quickly shut down the Virginia study and all further cannabis/tumor research even though the researchers demonstrated remarkable antitumor effects.”
“The endocannabinoid system plays an important role in the regulation of physiological and pathological conditions, including inflammation and cancer.
Hypoxia is a fundamental phenomenon for the establishment and maintenance of the microenvironments in various physiological and pathological conditions. However, the influence of hypoxia on the endocannabinoid system is not fully understood. In the present study, we investigated the effects of hypoxia on the endocannabinoid system in malignant brain tumors.
Although cannabinoid receptor (CB) engagement induces cell death in U-87 MG cells in normoxic conditions, CB agonist-induced death was attenuated in hypoxic conditions. These results suggest that hypoxia modifies the endocannabinoid system in glioblastoma cells.
Hypoxia-induced inhibition of the endocannabinoid system may aid the development of glioblastoma.”
“The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment.
RESULTS:
Cannabis sativa is a plant rich in more than 100 types of cannabinoids. Besides exogenous plant cannabinoids, mammalian endocannabinoids and synthetic cannabinoid analogues have been identified. Cannabinoid receptors type 1 (CB1) and type 2 (CB2) have been isolated and characterized from mammalian cells. Through cannabinoid receptor and non-receptor signaling pathways, cannabinoids show specific cytotoxicity against tumor cells, while protecting healthy tissue from apoptosis. The dual antiproliferative and proapoptotic effects of cannabinoids and associated signaling pathways have been investigated on a large panel of cancer cell lines. Cannabinoids also display potent anticancer activity against tumor xenografts, including tumors that express high resistance to standard chemotherapeutics. Few studies have investigated the possible synergistic effects of cannabinoids with standard oncology therapies, and are based on the preclinically confirmed concept of “cannabinoid sensitizers.” Also, clinical trials aimed to confirm the antineoplastic activity of cannabinoids have only been evaluated on a small number of subjects, with no consensus conclusions regarding their effectiveness.
CONCLUSIONS:
A large number of cannabinoid compounds have been discovered, developed, and used to study the effects of cannabinoids on cancers in model systems. However, few clinical trials have been conducted on the use of cannabinoids in the treatment of cancers in humans. Further studies require extensive monitoring of the effects of cannabinoids alone or in combination with standard anticancer strategies. With such knowledge, cannabinoids could become a therapy of choice in contemporary oncology.”
“Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The challenging problem in cancer treatment is to find a way to upregulate radiosensitivity of GBM while protecting neurons and neural stem/progenitor cells in the brain. The goal of the present study was upregulation of the cytotoxic effect of γ-irradiation in GBM by non-psychotropic and non-toxic cannabinoid, cannabidiol (CBD).
We emphasized three main aspects of signaling mechanisms induced by CBD treatment (alone or in combination with γ-irradiation) in human GBM that govern cell death: 1) CBD significantly upregulated the active (phosphorylated) JNK1/2 and MAPK p38 levels with the subsequent downregulation of the active phospho-ERK1/2 and phospho-AKT1 levels. MAPK p38 was one of the main drivers of CBD-induced cell death, while death levels after combined treatment of CBD and radiation were dependent on both MAPK p38 and JNK. Both MAPK p38 and JNK regulate the endogenous TRAIL expression. 2) NF-κB p65-P(Ser536) was not the main target of CBD treatment and this transcription factor was found at high levels in CBD-treated GBM cells. Additional suppression of p65-P(Ser536) levels using specific small molecule inhibitors significantly increased CBD-induced apoptosis. 3) CBD treatment substantially upregulated TNF/TNFR1 and TRAIL/TRAIL-R2 signaling by modulation of both ligand and receptor levels followed by apoptosis.
Our results demonstrate that radiation-induced death in GBM could be enhanced by CBD-mediated signaling in concert with its marginal effects for neural stem/progenitor cells and astrocytes. It will allow selecting efficient targets for sensitization of GBM and overcoming cancer therapy-induced severe adverse sequelae.”
“The endocannabinoid system has emerged as a considerable target for the treatment of diverse diseases.
In addition to the well-established palliative effects of cannabinoids in cancer therapy, phytocannabinoids, synthetic cannabinoid compounds as well as inhibitors of endocannabinoid degradation have attracted attention as possible systemic anticancer drugs.
As a matter of fact, accumulating data from preclinical studies suggest cannabinoids elicit effects on different levels of cancer progression, comprising inhibition of proliferation, neovascularisation, invasion and chemoresistance, induction of apoptosis and autophagy as well as enhancement of tumour immune surveillance.
Although the clinical use of cannabinoid receptor ligands is limited by their psychoactivity, nonpsychoactive compounds, such as cannabidiol, have gained attention due to preclinically established anticancer properties and a favourable risk-to-benefit profile.
Thus, cannabinoids may complement the currently used collection of chemotherapeutics, as a broadly diversified option for cancer treatment, while counteracting some of their severe side effects.” https://www.ncbi.nlm.nih.gov/pubmed/30019449
“Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. The challenging problem in cancer treatment is to find a way to upregulate radiosensitivity of GBM while protecting neurons and neural stem/progenitor cells in the brain. The goal of the present study was upregulation of the cytotoxic effect of γ-irradiation in GBM by non-psychotropic and non-toxic