

“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

“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.”
“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.”
“Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine.
The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient.
In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics. Knowledge based on proteins and molecules involved in the transport, action, and metabolism of cannabinoids in the human organism leads us to predict candidate genes which variations are responsible for the presence of the therapeutic and side effects of medical marijuana and cannabinoid-based drugs.
We can divide them into: receptor genes-CNR1, CNR2, TRPV1, and GPR55, transporters-ABCB1, ABCG2, SLC6A, biotransformation, biosynthesis, and bioactivation proteins encoded by CYP3A4, CYP2C19, CYP2C9, CYP2A6, CYP1A1, COMT, FAAH, COX2, ABHD6, ABHD12 genes, and also MAPK14. This review organizes the current knowledge in the context of cannabinoids pharmacogenetics according to individualized medicine and cannabinoid drugs therapy.”
https://www.ncbi.nlm.nih.gov/pubmed/28534260
“There is a feeling that the next milestone, after legal acceptance of medical marijuana, will be intensive pharmacogenetic-oriented study of individual populations, which hopefully explain the previous contradictory results and identify in the future genetic markers to personalize cannabinoids treatment.” https://link.springer.com/article/10.1007%2Fs13318-017-0416-z