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HIGHLIGHTS FROM CANNABINOID ANTI-TUMOR & ANTI-CANCER STUDIES

Highlights from numerous clinical studies and literature reviews demonstrating cannabinoids exhibit anti-tumor and anti-cancer activity and help in symptoms management in various types of cancers.

HIGHLIGHTS

An early study published 1975 looked at the antineoplastic activity of cannabinoids and showed that Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD).: Antineoplastic activity of cannabinoids – PubMed (nih.gov) https://pubmed.ncbi.nlm.nih.gov/1159836/ A E Munson, L S Harris, M A Friedman, W L Dewey, R A Carchman, PMID: 1159836 DOI: 10.1093/jnci/55.3.597

Other studies found cannabinoids, specifically CBD and THC Delta 9 good for helping cancer patients with symptoms of cancer treatments including: breakthrough nausea and vomiting, helps stimulate appetite, reduces cancer pain.  A summary can be found at Cannabinoids for Symptom Management and Cancer Therapy: The Evidence in: Journal of the National Comprehensive Cancer Network Volume 14 Issue 7 (2016) (jnccn.org)

The activation of CB receptors by cannabinoids is antitumorigenic in most cases, meaning it inhibits tumor cell proliferation, induces apoptosis in vitro, and blocks angiogenesis and tumor invasion/metastasis in vivo [35,46,51,52].

In vitro and in vivo preclinical cancer model evidence that cannabinoids block cancer proliferation signaling, tumor migration and cell division, and angiogenesis.

In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models

CBD in particular increases the susceptibility of tumor cells to the lymphokine-activated killer cells, which can result in cell lysis.37

Results indicated that activation of cannabinoid receptors, particularly CB2, may induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells.

Endogenous cannabinoids, synthetic or cannabis extracted from plants, can reduce tumor invasion and growth, induce tumor cell death, and inhibit tumor angiogenesis via cannabinoid receptor or receptor-independent pathways. Cannabinoid receptors appear to be highly expressed in pancreatic cancer compared with normal pancreatic tissue. CBD and THC appear to have antiproliferative and proapoptotic effects. CBD in a clinically relevant pancreatic cancer model improved survival outcomes when combined with gemcitabine. Clinical studies on the utility of cannabinoids in the treatment of pancreatic cancer are lacking and urgently needed

THC was found to induce the death of various human brain cancer cell lines and primary cultured human brain cancer cells by a process known as autophagy. Consistent with the in vitro data, administration of THC to mice with human tumors decreased tumor growth and induced the tumor cells to undergo autophagy. As analysis of tumors from two patients with recurrent glioblastoma multiforme (a highly aggressive brain tumor) receiving intracranial THC administration showed signs of autophagy, the authors suggest that cannabinoid administration may provide a new approach to targeting human cancers.

Cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.

CBD inhibits human breast cancer cell proliferation and invasion through differential modulation of the extracellular signal-regulated kinase (ERK) and reactive oxygen species (ROS) pathways, and that both pathways lead to down-regulation of Id-1 expression. Moreover, we demonstrate that CBD up-regulates the pro-differentiation factor, Id-2. Using immune competent mice, we then show that treatment with CBD significantly reduces primary tumor mass as well as the size and number of lung metastatic foci in two models of metastasis.

Induce cytotoxicity in leukemia cell lines: “We have shown that THC is a potent inducer of apoptosis, even at 1 x IC (50) (inhibitory concentration 50%) concentrations and as early as 6 hours after exposure to the drug. These effects were seen in leukemic cell lines (CEM, HEL-92, and HL60) as well as in peripheral blood mononuclear cells.” (20)

Another study from 2006 concludes cannabidiol can dramatically induce cell death in leukemia cells. Researchers of this study claim that cannabidiol may actually be a new and highly selective treatment for leukemia (21).

Other studies show that cannabinoids not only inhibit the growth of a broad spectrum of tumor cells but that they are effective agents to trigger apoptosis in human leukemia cells.

REFERENCES

Cannabinoids in cancer treatment: Therapeutic potential and legislation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387667/ Bosn J Basic Med Sci. 2019 Feb; 19(1): 14–23. doi: 10.17305/bjbms.2018.3532

Literature Review: Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer – Golnaz Sharafi,1 Hong He,1 and Mehrdad Nikfarjam*,1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352507/

The use of cannabinoids as anticancer agents GuillermoVelascoSoniaHernández-Tiedra1DavidDávila1MarLorente1 https://www.sciencedirect.com/science/article/pii/S0278584615001190

Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms Luciano De Petrocellis  1 Alessia LigrestiAniello Schiano MorielloMariagrazia IappelliRoberta VerdeColin G StottLuigia CristinoPierangelo Orlando, Vincenzo Di Marzo https://pubmed.ncbi.nlm.nih.gov/22594963/

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells Sean D McAllister  1 Rigel T ChristianMaxx P HorowitzAmaia GarciaPierre-Yves Desprez https://pubmed.ncbi.nlm.nih.gov/18025276/

Affiliations

Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis

Sean D McAllister  1 Ryuichi MuraseRigel T ChristianDarryl LauAnne J ZielinskiJuanita AllisonCarolina AlmanzaArash PakdelJasmine LeeChandani LimbadYong LiuRobert J DebsDan H MoorePierre-Yves Desprez https://pubmed.ncbi.nlm.nih.gov/20859676/

Affiliations

Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

Affiliations