The Endogenous Cannabinoid System (ECS) is concerned with the regulation of several essential peripheral and central physiological effects. Despite the multitude of actions performed by the ECS, the major focus of this paper is on its ability to control cellular proliferation since this opens entirely new therapeutic opportunities, like being used as an antitumor agent. Synthetic and endogenous cannabinoids can induce apoptosis of various tumor cells in-vivo and in culture. This paper will focus on the mechanism that underlies the effects of cannabinoids on tumor growth and its therapeutic application potentials.
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There are still gray areas regarding the mechanism surrounding effects of cannabinoids on tumor growth. Cannabinoids apoptosis induction has its foundation in ceramide production, ceramide being a sphingolipid messenger generated universally during apoptosis and a cellular messenger.
Two peaks of ceramide can be generated by exposing glioma cells to cannabinoid triggers. The mechanism via which cannabinoids produce ceramide has to do with the activation of serine palmitoyltransferase and de novo synthesis of ceramide. The prostate cells have also been shown to produce ceramide. Induction of apoptosis by anticancer drugs equally involves de novo ceramide biosynthesis. Also, a sustained and slow elevation of ceramide has been traced to the effector phase of death stimuli.
Caspases contribute to the effects of cannabinoids on tumor growth and are involved in the regulation of apoptotic death, caspases being a series of cysteine proteases that have specificity for aspartic acid residues, which gets activated during apoptosis. Caspases are divided into executioner caspases activated by proteolytic cleavage by other caspases and initiator caspases activated by protein-protein interaction. Cannabinoid agonists in certain cells can activate the major executioner caspase-3. Anandamide induces Caspase-3 activation measured by its protease activity and apoptosis of the rat pheochromocytoma PC-12 cells. The induction can, however, be prevented by N-acetylcysteine antioxidant. THC-induced apoptotic death accompanies the activation of caspase-3 by a CB1 receptor-dependent mechanism in cortical neurons.
Only limited results have been achieved from the studies involving prevention or risk of smoking and marijuana smoking. The outcomes of the results obtained are equally controversial. The first effort involves separating cannabinoids or THC effects from marijuana tar pyrolysis products. Multiple substances in marijuana that may work antagonistically, additively and synergistically manifest when taken together during marijuana smoking. Cannabis smoking can increase the risk of cancer of the lungs and aero-digestive tracts. There is equally a higher risk of airway biopsies histopathologic alterations with marijuana smoking, which is similar to what results from tobacco smoking.
Also, carcinogen-metabolizing enzyme CYP1A1 mRNA is increased by THC and marijuana tar extracts. This is a key step in tobacco-related cancer development. It has been shown via several publications that the smoking of cannabis can contribute to head and neck cancer development. However, no relationship between higher risk of cancer and marijuana use in another study conducted with 64855 participants. Bear in mind that the rate of respiratory tract cancers increases in individuals above 60 years.
The situation above is different from endocrine-related tumors. Also, a study shows that there is an increase in prostate cancer risk in males that have never smoked tobacco but have smoked cannabis. There is a relationship between cervical cancer and the use of cannabis in women. Endocrine tumor development can equally increase in rats when treated with marijuana after being treated with gamma irradiation.
Some epidemiological studies are already published about the action of isolated cannabinoids and THC on the development of cancer in humans. The effort is ongoing about clinical studies of the anti-tumoral effect of THC. The in-vivo experiments on the anticancer effects of THC along with other cannabinoids was done in experimental animals.
Synthetic chemists and biochemists have made paralleled efforts during the past years and have recorded meaningful progress in cellular proliferation regulation involving cannabis use. The various studies have led to the development of synthetic agents useful as valuable tools for elucidating some of the pathways underlying cannabinoids’ mechanism of action.
Most of the studies and results obtained above regarding the effects of cannabinoids on tumor growth were carried out in vitro or in vivo in experimental animals. Further studies are required to properly determine the actual effects of cannabis on tumor growth in humans, especially in terms of cannabinoid delivery.