Phytochemicals and Cannabinoids from Cannabis Spp. implicated in the treatment Cancer
Cancer happens when cells undergo genetic damage that results in uncontrolled proliferation to form a primary tumour. If the proliferation stops here, the cancer is benign. Malignant cancers are a result of metaplasia (irreversible change from one cell type to another), dyplasia (proliferation of immature cells of one type) and later anaplasia (loss of structural differentiation within cells). Successful metastasis of the tumour requires the ability of the cell to degrade the extracellular matrix, migrate, proliferate at a new site, and to stimulate vasculogenesis and angiogenesis (formation of new blood vessels). Solid cancers (all except leukaemia) have limited growth without adequate blood supply.
THC and cannabinoids have demonstrated anti-tumour effects in a number of cancers including:
- Brain (gliomas and glioblasts)
- Induction of cell death: THC readily crosses the blood brain barrier and causes selective apoptosis of glioma cells while exhibiting protection of astrocytes (normal glial cells in the brain and spinal cord). THC also activates the ceramide mediated death pathway leading to cell death and is able to diffuse into cells and destabilize the mitochondrial activity resulting in cell death.
- Inhibition of tumour cell growth: THC blocks the vascular endothelial growth factor responsible for the stimulation of vasculogenesis and angiogenesis thereby inhibiting tumour angiogenesis.
- Potentiating the effects of chemotherapy agents: THC causes inhibition of p-glycoprotein expression, which is responsible for the resistance to several chemotherapy drugs.
CBD has shown great potential as an anti-cancer agent. It has been implicated in the inhibition of tumour invasion and metastasis in lung cancer by up-regulating intracellular adhesion molecule-1. ICAM-1 has been negatively correlated with cancer metastasis. CBD has also reduced tumour burden and increased apoptosis in leukemic human cells, increased production of reactive oxygen species in human glioma cells leading to apoptosis, as well as proven efficacy in inducing cytoxicity in human breast carcinoma.
CBD also potentiates the effects of chemotherapy agents by inhibition of P-glycoprotein expression which is responsible for the resistance to several chemotherapy drugs.
Cannabigerol (CBG) and Cannabinol (CBN)
CBG and CBN has proven to be cytotoxic in breast cancer cells experimentally. CBD and has also shown potent TRPM8 blockade which may be useful in prostate cancer.
Cannabis terpenoids such as Myrcene, D-Limonene and Quercetin have also demonstrated ant-tumour activity.
Nausea and vomiting are major side effects of chemotherapy. Emesis in patients can be severe causing depression, anxiety and cessation of treatment. THC has effect on several neurotransmitters such as serotonin, GABA, glutamate and dopamine that mediate nausea and vomiting. Antagonism of these receptors typically result in anti-emesis, however antagonism of CB1 receptors by THC and other Cannabinoids produce anti-emesis.
In a comparative study between placebo and smoked ganja there was relief of nausea and vomiting with ganja. However, when compared with ondansetron, a potent anti-emetic, ondansetron proved to be more effective anti-emetic and anti-nausea agent.
In studies comparing THC to prochlorperazine there was at least equal statistical significance between the two. While, in another study using nabilone, a synthetic cannabinoid, it was shown that nabilone possessed anti-emetic and anti-nausea effects greater than that of prochlorperazine and that nabilone was also effective in patients who had proven unresponsive to prochlorperazine.
Recent studies have shown that the mechanism of action by which cannabidiol reduces toxin induced nausea and vomiting is by activation at the 5HT-1A receptor.
CB1 receptors in hunger centres of the hypothalamus increase food taste upon release of the hunger hormone, ghrelin. Reduction in ghrelin activity is mediated via release of chime into the duodenum, signalling satiety. Anorexia, weight loss and cachexia are associated with cancer patients.
Studies of weight loss in HIV and AIDS have shown significant increase in appetite and weight gain with administration of oral dronabinol compared to a placebo over a 4-6 weeks period. In addition, studies in cancer patients have shown that THC may also increase the pleasure value and satisfaction of food while improving appetite resulting in weight gain.
Cancer pain is usually associated with inflammation, nerve damage or invasion of bone or other sensitive areas. The identification of CB1 and CB2 receptors as well as some understanding of the endocannabinoid pathway in the body has vastly improved the therapeutic potential of ganja. CB1 receptors are more widely distributed in the central nervous system, and peripheral nerve terminals with minimal CB2 presence. By contrast CB2 receptors are more widely distributed in peripheral cells.
Reports have shown increased pain relief with the co-administration of CBD with THC than with THC only. In addition, studies on the effects of THC and CBD combination proved it to be more efficacious than opioids only in the relief of pain particularly in advanced cancer patients and pain not fully managed by opioids. This results in a lower dose regimen of opioids.
Adverse effects were shown to be dose related with only the highest dose reporting side effects. THC: CBD has shown no negative drug interactions and has not shown dependence in over 1500 patients.
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