Cannabinoids and the treatment of cancer

Cancer is a broad term used for diseases in which abnormal cells divide without control and are able to invade other tissues, causing metastases and high rates of mortality and morbidity.

It is not just one disease but many: more than 100 different cancers are well-typified by the World Health Organisation and there are probably hundreds, if not thousands, of types according to molecular and genetic profiling.

In simple terms cancers have a way of preventing apoptosis, the naturally occurring sequence of steps that take place in the body to induce harmful cells to commit suicide.

Apoptosis provides the checks and balances on the process of natural cell division and regeneration which allows the body to remove cells that aren’t needed. For example, as the brain develops the body creates millions more cells than it requires, those not forming synaptic connections can undergo apoptosis so the remaining cells can function as needed.

Cells may also become damaged or undergo some type of infection and the way the body removes them without causing harm to other cells is to initiate apoptosis. Cells recognise viruses and gene mutations and can induce death to prevent the damage from spreading.

Apoptosis can also be triggered externally by chemical substances that bind to specific receptors on the cell surface, which is how white blood cells combat infection and activate apoptosis in infected cells. It is also why cannabis is believed to be a potent treatment for cancer.

Some types of cancers persist as a result of a cell's inability to trigger apoptosis. Tumours develop by integrating their genetic material with the host cell’s DNA, with such cancers initiating the production of proteins that stop apoptosis from occurring.

Within the body the endocannabinoid system plays an important role in regulating apoptosis and is a crucial component in maintaining the body’s overall equilibrium.

The endocannabinoid system is responsible for regulating the balance of the body’s immune response, including communication between cells, as well as appetite, metabolism, memory and many other functions.

The endocannabinoid system (ECS) involves three core components: endocannabinoids, receptors and enzymes.

Endocannabinoids, also called endogenous cannabinoids, are molecules made by the body to keep internal functions running smoothly. Two types of endocannabinoids exist: anandamide (AEA) and 2-arachidonoylglyerol (2-AG).

The body produces them as needed, making it difficult to know what typical levels are for each.

Endocannabinoid receptors are found throughout the body, with endocannabinoids binding to them in order to signal that the ECS needs to take action.

There are two main endocannabinoid receptors: CB1 receptors, which are mostly found in the central nervous system; and CB2 receptors, which are mainly found in the peripheral nervous system, especially immune cells.

Endocannabinoids can bind to either receptor. The effects that result depend on where the receptor is located and which endocannabinoid it binds to.

For example, endocannabinoids might target CB1 receptors in a spinal nerve to relieve pain. Others might bind to a CB2 receptor in the body’s immune cells to signal that it’s experiencing inflammation, a common sign of autoimmune disorders.

Enzymes are responsible for breaking down endocannabinoids once they’ve carried out their function. There are two main types: fatty acid amide hydrolase, which breaks down AEA; and monoacylglycerol acid lipase, which typically breaks down 2-AG.

So the endocannabinoid system consists of several integrated mechanisms, with enzymes responsible for creating and destroying endocannabinoids; receptor sites on cells to receive endocannabinoids; and endocannabinoids themselves that are naturally produced by the body.

And it is through this system that cannabis interacts with the body due to naturally occurring cannabinoids found in the plant working in the same way as endocannabinoids.

Cannabinoids are produced and stored within the trichomes (crystals) of the plant, which give cannabis flowers their shiny and sparkly appearance.

As a result cannabis can trigger many beneficial effects, with the cannabis plant producing more than 80 different cannabinoids, including THC and CBD, which are the most prevalent and best understood.

Many strains of cannabis are cultivated with higher levels of THC (tetrahydrocannabinol), known for its psychoactive properties and the reason people feel “high” after ingesting it. CBD (cannabidiol) is a non-psychoactive cannabinoid and works to counteract the high. CBD also has numerous benefits, such as anti-inflammatory and neuro-protective properties.

While THC and CBD are the most well-known cannabinoids, there are many others found in cannabis that offer health benefits. Some of these include cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC).

Although CB1 and CB2 are the major cannabinoid receptors, they aren’t the only ones, but were the first discovered and remain the best-studied.

The CB1 receptors are one of the most abundant receptor types in the brain. These are the receptors that interact with THC to get people “high”; while CB2 receptors are more abundant outside of the nervous system, in places like the immune system. However, both receptors can be found throughout the body.

It is widely believed that 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.

Every cell has a family of “interconvertible sphingolipids” that manage the life and death of the cell. This profile is called the “Sphingolipid Rheostat” and if “endogenous ceramide” is high then cell death is imminent. If ceramide is low, the cell is strong.

Within most cells there is a nucleus, numerous mitochondria (hundreds to thousands) and various other organelles in the cytoplasm. When THC connects to the receptor the cancer cell dies, not because of cytotoxic chemicals, but because of a tiny shift in the mitochondria.

The purpose of the mitochondria is to produce energy for the cell. As ceramide starts to accumulate, turning up the Sphingolipid Rheostat, it increases the mitochondrial membrane 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, which disrupts calcium metabolism in the mitochondria, and disrupts the “cellular lysosome”, the cell’s digestive system that provides nutrients for all cell functions.

So THC’s ability to stimulate the body’s production of ceramide, and other sphingolipids, can actively inhibit pro-survival pathways in cells, effectively terminating the cancer cell’s ability to survive.

Given this scenario you’d think cannabis was a major breakthrough in the treatment of cancer, but there’s just one problem… after decades of prohibition the medical world seems very slow to pick up on its healing powers, with cannabis derivatives still being largely ignored by health professionals afraid to deviate from traditional treatments such as chemotherapy and radiotherapy.

Surely the science can no longer be ignored, cannabis offers a key to unlocking the endocannabinoid system and its incredible ability to regulate health… it’s time to start using it!