05 October 2015

Cannabis Kills Cancer Cells

Despite a deficiency in human trials, there are a significant amount of studies that show compounds found within cannabis, known as cannabinoids, have anti-cancer properties. The United States’ federally funded National Institute of Health even goes as far as to state on their website that: 

"Cannabinoids may cause anti-tumour effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumour angiogenesis invasion and metastasis".

Dennis Hill earned a degree in biochemistry from the University of Houston, worked in medical research at the University of Texas and as of September 2015, resides in California. Following a biopsy in 2010, he was diagnosed with aggressive Stage 4 adenocarcinoma of the prostate. A digital exam revealed metastatic lesions in the bladder and rectum. “Opting out of radiation, chemo and surgery, I chose cannabis extract”, he said. “Within six months the cancer was in remission. I never really noticed any dramatic changes; the cancer just went away. After three months, the primary tumour was gone; after three more months, the metastatic lesions were gone”. Utilising his expert knowledge of human biochemistry, Dennis explains in detail exactly what occurs when a cancer patient ingests cannabinoids.

Let us look first at tetrahydrocannabinol (THC) and observe THC is a natural fit for the CB1 cannabinoid receptor on the cancer cell surface. When THC hits the receptor, the cell generates ceramide that disrupts the mitochondria, closing off energy for the cell. Disruption of the mitochondria releases cytochrome c and reactive oxygen species into the cytosol, hastening cell death. It is notable this process is specific to cancer cells. Healthy cells have no reaction to THC at the CB1 receptor. The increase in ceramide also disrupts calcium metabolism in the mitochondria, completing the demise to cell death.

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The other cannabinoid we know is effective in killing cancer cells is cannabidiol (CBD). The primary job of CBD in the cancer cell is to disrupt the endoplasmic reticulum (ER) through the wrecking of the calcium metabolism, pushing calcium into the cytosol. This always results in cell death. Another pathway for CBD to effect cancer cell death is the caspase cascade, which breaks down proteins and peptides in the cell. When this happens the cell cannot survive. Again, these processes are specific to cancer cells, no normal cells are affected. Certain cannabinoids destroy cancerous tumours by working symbiotically with our body’s Endocannabinoid System (ECS):

"The Endocannabinoid System (ECS) started revealing itself to researchers in the 1940's and by the late 1960's the basic structure and functionality had been laid out. Today we know the ECS is a comprehensive system of biochemical modulators that maintain homoeostasis in all body systems including the central and peripheral nervous systems, all organ systems, somatic tissues and all metabolic biochemical systems, including the immune system".

This homoeostatic matrix is not a recent evolutionary twist just for humans; we find the ECS in every chordate creature for the last 500 million years. It is a fully mature biochemical technology that has maintained health and metabolic balance for most of the history of life itself.

The two major interactive systems within the ECS are (1) The cannabinoid receptors that we find on all cell surfaces and neurological junctions and (2) The endocannabinoids that fit the receptors to trigger various metabolic processes. Looking at a cannabinoid receptor distribution map we see that CB1 receptors, most sensitive to anandamide, are found in the brain, spinal and peripheral nerves. CB2 receptors preferred by 2-Arachidonoylglycerol (2-AG) are found largely in the immune system, primarily the spleen. A mix of CB1 and CB2 receptors are found throughout the rest of the body including the skeletal system. And yes, 2-AG or CBD will grow new trabecular bone. It is also useful to note that both anandamide and 2-AG can activate either CB1 or CB2 receptors.

The nature of the endocannabinoids are functionally much like neurotransmitters, but structurally are eicosanoids in the family of signaling sphingolipids. These signaling cannabinoids keep track of metabolic systems all over the body. This information is shared with the nervous system and the immune system so that any imbalance is attended to. If the body is in chronic disease or emotional stress, the immune system can fall behind and lose control of compromised systems. It is here that phytocannabinoids can pitch in to support the stressed body in a return to health. The cannabis plant provides analogues of the body’s primary signaling cannabinoids. Tetrahydrocannabinol (THC) is mimetic to anandamide and CBD is mimetic to 2-AG, and has the same affinity to CB1 and CB2 receptors, providing the body with additional support for the immune and endocannabinoid systems.


Phytocannabinoids supercharge the body’s own ECS by amping up the response to demand from the immune signaling system in two modes of intervention: one, of course, is in bonding with the cannabinoid receptors; the other is in regulation of innumerable physiological processes, such as cannabinoid’s powerful neuroprotective and anti-inflammatory actions, quite apart from the receptor system. It is interesting to note here that the phytocannabinoids and related endocannabinoids are functionally similar, but structurally different. As noted above, anandamide and 2-AG are eicosanoids while THC and CBD are tricyclic terpenes.

The (US) National Institutes of Health tells us that THC is the best known because of its signature psychotropic effect. This government report shows THC to be effective as an anti-cancer treatment, an appetite stimulant, analgesic, anti-emetic, anxiolytic and sedative. There is a plentiful supply of research articles and personal testaments that show the efficacy of cannabis effecting cancer remission. However, only a few point to the mechanism by which the cancer cells die. To understand this better we need to know what metabolic processes provide life to the cells. There are two structures in most cells that sustain life; one is the mitochondria and the other is the ER (endoplasmic reticulum). The mitochondria primarily produce adenosine triphosphate (ATP) that provides the necessary energy. The ER is a loosely bound envelope around the cell nucleus that synthesises metabolites and proteins directed by the nuclear DNA that nourish and sustain the cell …

In every cell there is a family of interconvertible sphingolipids that specifically manage the life and death of that cell. This profile of factors is called the ‘Sphingolipid Rheostat’. If ceramide (a signaling metabolite of sphingosine-1-phosphate) is high, then cell death (apoptosis) is imminent. If ceramide is low, the cell will be strong in its vitality. Very simply, when THC connects to the CB1 or CB2 cannabinoid receptor site on the cancer cell, it causes an increase in ceramide synthesis which drives cell death. A normal healthy cell does not produce ceramide in the presence of THC, thus is not affected by the cannabinoid.

The cancer cell dies, not because of cytotoxic chemicals, but because of a tiny little shift in the mitochondria. Within most cells there is a cell nucleus, numerous mitochondria (hundreds to thousands) and various other organelles in the cytoplasm. The purpose of the mitochondria is to produce energy (ATP) for cell use. As ceramide starts to accumulate, turning up the Sphingolipid Rheostat, it increases the mitochondrial membrane pore permeability to cytochrome c, a critical protein in energy synthesis. Cytochrome c is pushed out of the mitochondria, killing the source of energy for the cell.

Ceramide also causes genotoxic stress in the cancer cell nucleus generating a protein called p53, whose job it is to disrupt calcium metabolism in the mitochondria. If this weren’t enough, ceramide disrupts the cellular lysosome, the cell’s digestive system that provides nutrients for all cell functions. Ceramide, and other sphingolipids, actively inhibit pro-survival pathways in the cell leaving no possibility at all of cancer cell survival. The key to this process is the accumulation of ceramide in the system. This means taking therapeutic amounts of cannabinoid extract, steadily, over a period of time, keeping metabolic pressure on this cancer cell death pathway. How did this pathway come to be? Why is it that the body can take a simple plant enzyme and use it for healing in many different physiological systems? This endocannabinoid system exists in all animal life, just waiting for it’s matched exocannabinoid activator.

This is interesting. Our own ECS covers all cells and nerves; it is the messenger of information flowing between our immune system and the central nervous system (CNS). It is responsible for neuroprotection and micro-manages the immune system. This is the primary control system that maintains homoeostasis: our wellbeing … Endocannabinoids have their origin in nerve cells right at the synapse. When the body is compromised through illness or injury it calls insistently to the ECS and directs the immune system to bring healing. If these homoeostatic systems are weakened, it should be no surprise that exocannabinoids perform the same function. It helps the body in the most natural way possible.

To see how this works we visualise the cannabinoid as a three dimensional molecule, where one part of the molecule is configured to fit the nerve or immune cell receptor site just like a key in a lock. There are at least two types of cannabinoid receptor sites, CB1 (CNS) and CB2 (immune). In general CB1 activates the CNS messaging system, and CB2 activates the immune system, but it’s much more complex than this. Both THC and anandamide activate both receptor sites. Other cannabinoids activate one or the other receptor sites. Among the strains of cannabis, Cannabis sativa tends toward the CB1 receptor, and Cannabis indica tends toward CB2. So sativa is more neuroactive and indica is more immunoactive. Another factor here is that sativa is dominated by THC cannabinoids and indica can be higher in CBD.

It is known that THC and CBD are biomimetic to anandamide and AG-2, that is, the body can use both interchangeably. Thus, when stress, injury, or illness demand more from endogenous anandamide than can be produced by the body, its mimetic exocannabinoids are activated. If the stress is transitory, then the treatment can be transitory. If the demand is sustained, such as in cancer, then treatment needs to provide sustained pressure of the modulating agent on the homoeostatic systems. Typically CBD gravitates to the 5-HT1A and vanilloid receptors. CBD stimulates production of anandamide and AG-2, endogenous cannabinoids that are agonists for CB-1 and CB-2 receptors. From there, immune cells seek out and destroy cancer cells. Interestingly, it has been shown that THC and CBD cannabinoids have the ability to kill cancer cells directly without going through immune intermediaries. THC and CBD hijack the lipoxygenase pathway to directly inhibit tumor growth. As a side note, it has been discovered that CBD inhibits anandamide re-uptake. Here we see that CBD helps the body preserve its own natural endocannabinoid by inhibiting the enzyme that breaks down anandamide.

In 2006, researchers in Italy showed the specifics of how CBD kills cancer. CBD stimulates what is known as the Caspase Cascade, that kills the cancer cell. First, let’s look at the nomenclature, then to how Caspase kills cancer. Caspase is an aggregate term for all cysteine-aspartic proteases. The protease part of this term comes from prote (from protein) and -ase (destroyer). Thus the caspases break down proteins and peptides in the moribund cell. This becomes obvious when we see caspase-3 referred to as the executioner. In the pathway of apoptosis, other caspases are brought in to complete the cascade.

Even when the cascade is done and all the cancer is gone, CBD is still at work healing the body. CBD also shuts down the Id-1 gene; a gene that allows metastatic lesions to form. Fundamentally this means that treatment with cannabinoids not only kills cancer through numerous simultaneous pathways, but prevents metastasis. What’s not to like … Nature has designed the perfect medicine that fits exactly with our own immune system of receptors and signaling metabolites to provide rapid and complete immune response for systemic integrity and metabolic homoeostasis.

What advice would Dennis Hill dispense to somebody with terminal cancer who is looking into the possibility of utilising cannabis oil? He replied; “Many who have sought out cannabis as a last resort have recovered. It’s never too late”.

Below is a video of Dennis Hill explaining how cannabinoids cause cancer cells to die:

Also, Early phytocannabinoid chemistry to endocannabinoids and beyond
For a few simple definitions of some of the more scientific terms used in this article, try Granny Storm Crow's List 'Mini Dictionary'. 
For further reading on Cannabis and cancer, the following was collated for another article on Dennis Hill:
University of Naples Federico II, Institute of Biomolecular Chemistry and Endocannabinoid Research Group, Italy. Department of Medicinal Chemistry and Natural Products, Israel - Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb
National Cancer Institute, National Institutes of Health, USA - Cannabis and Cannabinoids–for health professionals (PDQ®)

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