Cancer

It is well established that Cannabis provides palliative effects on some cancer associated symptoms such as appetite stimulation, pain relief, antiemetic effects and improved sleep. More intriquing is that research obtained during the last fifteen years supports the theory that the molecular compounds (Cannabinoids) found in Marijuana can reduce tumor growth in animal models of cancer. Think of it like the tumor getting shellacked and suffocates to death.

The potential benefits of medicinal Cannabis for people living with cancer include antiemetic effects, appetite stimulation, pain relief, and improved sleep. In the practice of integrative oncology, the health care provider may recommend medicinal Cannabis not only for symptom management but also for its possible direct anti-tumor effect.National Cancer Institute

Cannabinoids have been shown to activate a process that causes death of cancer cells. That process is triggered with an Endoplasmic Reticulum stress (a cellular response process that is triggered by a number of conditions) related pathway that leads to the stimulation of a natural physiological process to eliminate dead cells, called autophagy (in animal models). This is what brings about cancer cell death. In addition, Cannabinoids inhibit the tumor’s ability to grow new blood vessels and decreases the cancer cell’s ability to spread.

Research into how Cannabis and its Cannabinoids’ anti-cancer action and possible strategies to develop Cannabinoid based combinational therapies to fight cancer have begun.

The Endocannabinoid System

The Endocannabinoid System, constituted by the Endocannabinoids, their receptors and the proteins involved in the synthesis, transport and degradation of Endocannabinoids, exerts numerous regulatory functions in the human body (mammals) (1)(2). Therefore, the pharmacological control of the Endocannabinoid System is being investigated for the treatment of many different diseases. And believe it or not, a lot of good research is taking place in American academia, such as University of California, Los Angeles (UCLA), The Center for Medicinal Cannabis Research at the University of California, San Diego (UCSD), and throughout the United States.

Endocannabinoids Role In Cancer Tumor Progression

Interestingly, as the last decade advanced the science communities grasp of the medicinal benefits Cannabinoids, a large body of evidence has shown that the Endocannabinoid System plays a role in tumor procreation and progression too. In most cases, the reports show that the levels of Endo-Cannabinoids and their receptors, CB1 and CB2, are increased in cancer, a situation that frequently correlates with tumor aggressiveness (3).

Endocannabinoids Anandamide and 2-Arachidonoylglycerol (2-AG) have been shown to be over expressed in several types of tumors including glioblastoma multiforme (GBM), meningioma, pituitary adenoma, prostate and colon carcinoma and endometrial sarcoma (4). Additionaly, circulating Endocannabinoid levels have been associated with increased disease progression in a mouse model of metastatic melanoma and in human samples (5).

Regarding Cannabinoid receptor CB2, a correlation between its expression, histological grade and prognosis has been demonstrated in breast cancer (6) and glioma (7). There is more evidence pointing to the increased levels of Endocannabinoids and their receptors playing a role in other cancers such as pancreatic, skin and leukemias.

Cannabinoid Anti-Cancer Activity

With evidence that Endo-Cannabiniods play a role in tumor origination and progression, there is also years of research demonstrating that Cannabinoid receptors play a role in anti-tumor effects in cancer, in experimental animal models, that supports the pharmacological stimulation of CB receptors as treatment for cancer.

Treating Cancer with Cannabinoids promotes cell death, impairs the tumor’s ability to grow new blood vessels (a process called angiogenesis), and blocks the tumor’s invasion of other cells and controls metastasis. Think of it as the Cannabinoids surround the tumor, and suffocate it by shellacking it and preventing it from growing new blood vessels.

Cannabinoids Induce Cancer Cell Death

The mechanism of Cannabinoids anti-cancer process, at least largely, relies on the ability to stimulate the natural process in which the body deals with the destruction of apoptic cancer cells. This process is called autophagy (8).

It gets bit complicated but I will try to simplify. THC binds Cannabinoid receptors, which then leads to the stimulation of sphingolipid synthesis de novo. This process triggers the ER stress related pathways mentioned above. The ER is prompted by the up-regulation of something they call the transcriptional co-activator nuclear protein 1 (9). The stimulation of this pathway promotes a natural process that can lead to cell death.

UNDER CONSTRUCTION…MORE COMING

The above is sourced from:
Guillermo Velasco, Sonia Hernández-Tiedra, David Dávila, and Mar Lorente The Use of Cannabinoids as Anti-Cancer Agents Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University of Madrid, Spain Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Spain - Full Paper

1) Katona, I., Freund, T.F., 2008. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med 14 (9), 923–930.
2) Pacher, P., Batkai, S., Kunos, G., 2006. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (3), 389–462.
3) Malfitano, A.M., Ciaglia, E., Gangemi, G., Gazzerro, P., Laezza, C., Bifulco, M., 2011. Update on the endocannabinoid system as an anticancer target. Expert Opin Ther Targets 15
(3), 297–308.
4) Pisanti, S., Borselli, C., Oliviero, O., Laezza, C., Gazzerro, P., Bifulco, M., 2007. Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy. J Cell Physiol 211 (2), 495–503.
5) Sailler, S., Schmitz, K., Jager, E., Ferreiros, N., Wicker, S., Zschiebsch, K., et al., 2014. Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans. Oncoscience 1 (4), 272–282.
6) Caffarel, M.M., Sarrio, D., Palacios, J., Guzman, M., Sanchez, C., 2006. Delta9- tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res 66 (13), 6615–6621.
7) Sanchez, C., de Ceballos, M.L., del Pulgar, T.G., Rueda, D., Corbacho, C., Velasco, G., et al., 2001. Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res 61 (15), 5784–5789.
8) Velasco, G., Sanchez, C., Guzman, M., 2012. Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer 12 (6), 436–444.
9) Armstrong, J.L., Hill, D.S., McKee, C.S., Hernandez-Tiedra, S., Lorente, M., Lopez-Valero, I., et al., 2015. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol 135 (6), 1629–1637.

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