How It Works (Abstract) by Dennis Hill
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
The longer version
Here, Dennis Hill explains the inner workings of cancer death-by-Cannabinoids:
Cannabinoids and Cancer
Cancer-specific Cytotoxicity of Cannabinoids
By Dennis Hill
First let’s look at what keeps cancer cells alive, then we will come back and examine how the cannabinoids CBD (cannabidiol) and THC (tetrahydrocannabinol) unravels cancer’s aliveness.
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 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 well being.
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 healing. 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 is predominately CBD (cannabidiol).
It is known that THC and CBD are biomimetic to anandamide, 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 densely packed CB2 receptors in the spleen, home to the body’s immune system. 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 reuptake. Here we see that cannabidiol 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 Cannabidiol (CBD) kills cancer. When CBD pairs with the cancer cell receptor CB-2 it 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. Its pairing at CB-2 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. 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.
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
The longer version
Here, Dennis Hill explains the inner workings of cancer death-by-Cannabinoids:
Cannabinoids and Cancer
Cancer-specific Cytotoxicity of Cannabinoids
By Dennis Hill
First let’s look at what keeps cancer cells alive, then we will come back and examine how the cannabinoids CBD (cannabidiol) and THC (tetrahydrocannabinol) unravels cancer’s aliveness.
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 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 well being.
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 healing. 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 is predominately CBD (cannabidiol).
It is known that THC and CBD are biomimetic to anandamide, 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 densely packed CB2 receptors in the spleen, home to the body’s immune system. 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 reuptake. Here we see that cannabidiol 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 Cannabidiol (CBD) kills cancer. When CBD pairs with the cancer cell receptor CB-2 it 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. Its pairing at CB-2 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. 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.
