Cannabinoids Show Promising Anti-cancer Effects In The Case Of Glioblastoma

Glioblastoma is one of the most dangerous and deadly brain cancers. In spite of the forms of cancer therapy, which usually consists of surgical resection (removal of neoplastic lesion to the greatest possible extent), radiation therapy, chemotherapy with temozolomide (TMZ), over 95% of patients with glioma die within 5 years of diagnosis.

Therefore, there is an urgent need to develop new therapeutic strategies against this disease. Increasing evidence suggests that cannabinoids have anti-cancer activity and can be successfully used to treat this cancer

Treating Glioblastoma with cannabis oil

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What’s the efficacy of cannabinoids in glioblastoma therapy, both in vitro experiments, preclinical experiments ( animal models) and inpatient studies?

Human gliomas are deadly and advanced cancer which affects the central nervous system. Their occurrence in adults is 0.59-3.69 cases per 100,000 people. The vast majority of gliomas develop de novo (primary gliomas), although they may also be evaluated in lower grade gliomas (secondary gliomas).

The primary type of glioma is more common in male cancer patients, while secondary gliomas are more likely to affect women. The average age of patients for primary and secondary types of glioblastoma is within 62 to 45 years, respectively.

Characteristics of Glioma

Glioma is extremely aggressive cancers. The tumors are characterized by high cell proliferation (multiplication) and angiogenesis (formation of new blood vessels), which causes a rapid development of neoplastic lesions.

Glioblastoma cells are also characterized by high ability to migrate — invasive properties that allow them to spread in the brain parenchyma. In addition, this type of tumor contains a subpopulation of stem cells-capable of unlimited divisions, which are partly responsible for the high resistance to conventional chemotherapy treatment. Thus, the high recurrence of this cancer type.

The need for more therapeutic strategies

Recent advances in the field of molecular pathology have identified various subtypes of glioma, which paved the way for more individualized therapeutic strategies. Nevertheless, glioblastoma treatment is currently still very limited, hence there is an urgent need to further understand the molecular mechanisms involved in the progression of this type of cancer and consequently seek for measures that would limit its occurrence.

Results from research studies

A large number of studies was carried out to ascertain the direct effect of cannabinoids on neoplastic changes caused by glioblastoma. Based on the results of the experiments, it was concluded that the therapeutic effect of a given group of compounds, among others, were responsible for limiting tumor growth by inhibiting cell proliferation, reduction of angiogenesis process, and also the induction of apoptosis (programmed cell death) of stem cancer cells.

Cannabinoids receptors (cb1 and cb2)

Modulation of tumor growth may also be affected by cannabinoid receptors – CB1 and CB2. The expression of these receptors was detected in glioma cell lines and in primary tumor cells from patients suffering from glioma. There is evidence that large amounts of CB2 receptors are found in high-grade glioma cells. In addition, CB2 expression positively correlates with the degree of malignancy.

On the contrary, the role of CB1 receptors still needs to be established due to the fact that various literature data provide different information about their function in modified tumor tissues.

Anti-tumor effects of cannabinoids

Nevertheless, the anti-tumor effect of cannabinoids has been found in many in vitro (cell line) and in vivo (animal model) studies. In such experiments, the antitumor effects of a combination of cannabinoids (in particular THC and CBD) were also investigated, and it was concluded that the anti-tumor effect of THC increased in combination with co-administration of CBD.

The therapeutic potential of the combination of THC and CBD has also been tested in combination with standard temozolomide chemotherapy (TMZ) or with simultaneous radiotherapy.

In mouse experiments, tumor size was reduced by co-administration of tetrahydrocannabinol with CBD and temozolomide compared to the effects obtained with THC with CBD or TMZ alone.

In another experiment, therapy using THC and CBD increased the effectiveness of radiotherapy in an animal model of glioma.

The beneficial effects of cannabinoids in preclinical studies led researchers to carry out experiments involving a small group of patients (preliminary phase of research).

Cannabinoids show promising anti-cancer effects in the case of glioblastoma

Phase I

Participants: 9 Glioma patients

Phase I clinical trial in the treatment of patients with glioma showed a good safety profile for tetrahydrocannabinol (THC). Intravenous THC administration in nine patients with actively growing glioma decreased the proliferation of tumor cells and induced enhanced apoptosis (cell death).

In addition, cannabinoids promoted the survival of healthy cells that are brain structural elements, including oligodendrocytes, astrocytes, and neuronal neuron cells. The tumor-specific cytostatic/cytotoxic effects of cannabinoids are therefore of great importance in the treatment of glioma.

Phase II

Participants: 21 Glioma patients

Phase II studies included an assessment of the efficacy of administering a mixture of THC and CBD in Sativex, combined with intense chemotherapy drug temozolomide in patients with glioblastoma. The study involved 21 adult patients with histopathologically confirmed glioma diagnosis (according to Karnofsky score of 60% or more).

The control group received only temozolomide, and the annual survival rate for patients in this group was approximately 44%. Patients in the study group in addition to chemotherapy additionally received a maximum of 12 sprays of Sativex aerosol (daily), thus providing 100 ml of a solution containing 27 mg/ml THC and 25 mg/ml CBD. The annual survival rate in this group of patients was 83%.

In contrast, the median survival of patients in the study group was over 662 days compared to 369 days in the control group.

Conclusion

In conclusion, cannabinoids show promising anti-cancer effects in the case of glioblastoma, through the influence on molecular mechanisms including apoptosis, angiogenesis (formation of blood vessels), invasiveness of tumor cells or interaction with cancer stem cells.

The action of cannabinoids can be potentially enhanced by the simultaneous use of two compounds of this type (for example THC and CBD) or in combination with other methods of cancer therapy (chemotherapy, radiotherapy).

However, this requires a detailed understanding of the molecular mechanisms and pharmacological effects induced by cannabinoids. Ultimately, these discoveries may favor the development of improved therapeutic strategies against glioblastoma, breast cancer, and possibly other brain tumors or nervous system diseases.

Obviously, more reasons why cannabis should be legalized everywhere in the world

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