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 sustains life; one is the mitochondria, and the other is the endoplasmic reticulum. The mitochondria primarily produces adenosine triphosphate (ATP) that provides the necessary energy. The endoplasmic reticulum (ER) is a loosely bound envelope around the cell nucleus that synthesizes metabolites and proteins directed by the nuclear DNA that nourish and sustain the cell.

Let us look first at tetrahydrocannabinol (THC) and observe that 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 that 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.

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 through 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.

How Do Cannabinoids Kill Cancer?

The Endocannabinoid System (ECS) started revealing itself to researchers in the 1940s and by the late ‘60s the basic structure and functionality had been laid out. Today we know the ECS is a comprehensive system of biochemical modulators that maintain homeostasis 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 homeostatic matrix is not a recent evolutionary twist just for humans; we find the Endocannabinoid System 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, that are most sensitive to anandamide, are found in the brain, spinal nerves, 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 cannabidiol (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 Endocannabinoid System 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 National Institutes of Health tell 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, antiemetic, 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 sustains life; one is the mitochondria, and the other is the endoplasmic reticulum. The mitochondria primarily produces adenosine triphosphate (ATP) that provides the necessary energy. The endoplasmic reticulum (ER) is a loosely bound envelope around the cell nucleus that synthesizes metabolites and proteins directed by the nuclear DNA that nourish and sustain the cell.

Let us look first at tetrahydrocannabinol (THC) and observe that 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. The cancer cell dies, not because of cytotoxic chemicals, but because of a tiny little shift in the mitochondria.

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.

Disruption of the mitochondria releases cytochrome c and reactive oxygen species into the cytosol, hastening cell death. It is notable that 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. Within most cells there is a cell nucleus, numerous mitochondria (hundreds to thousands), and various other organelles in the cytoplasm. 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.

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 through 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.

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 endocannabinoid system 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 homeostasis: our wellbeing.
Just out of curiosity, how does the work get done at the cellular level, and where does the body make the endocannabinoids? Here we see that 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 endocannabinoid system and directs the immune system to bring balance. If these homeostatic 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 visualize 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, C. sativa tends toward the CB1 receptor, and C. 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 than sativa in CBD (cannabidiol).

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 homeostatic 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 cannabidiol helps the body preserve its own natural endocannabinoid by inhibiting the enzyme that breaks down anandamide.

Research shows that THC is metabolized to 11-Hydroxy-THC in the liver after oral consumption. We also know that 11-Hydroxy-THC is more potent than THC. This suggests that cannabis via smoking, or suppository is weaker clinically than oral since it misses the first-pass in the liver to convert. If you want to avoid the mental effects, use 1:1 THC:CBD. The CBD knocks out the mental effect while maintaining potency of the cannabis extract. My opinion is that oral cannabis extract with equal parts THC and CBD is the ideal cancer killer without the mental effects. The cannabinoids work in concert to kill cancer; this is known as the entourage effect; THC disrupts the cancer cell mitochondria, and CBD disrupts the cell’s endoplasmic reticulum, bringing certain cell death.

Also good to know that hydroxy-THC has a stronger mental effect than unmodified THC. If the cannabis oil has not been decarboxylated (to delete the acidic carboxyl radical), then there will be no effect of the THC. This is the most important issue is using cannabis to kill cancer. Without decarboxylation, the THC cannot fit the CB1 receptor on the cancer cell to cause cell death.

In 2006, researchers in Italy showed the specifics of how Cannabidiol (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 in 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. Cannabidiol 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 (the entourage effect), but prevents metastasis. What’s not to like. One researcher says this: CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic carcinoma leading to the down-regulation of tumor aggressiveness.

This brief survey touches lightly on a few essential concepts. Mostly I would like to leave you with an appreciation that 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 homeostasis.

Author: Dennis Hill