To fully appreciate the potential of cannabinoid therapeutics, we need to understand the way our bodies are made to process and react to signals coming from outside and from within ourselves, and how we function as a whole even though we are made up of millions of individual cells.
In order for cells with different functions to work together to keep the body functioning, they must be able to obtain enough energy to stay alive and to communicate with other cells. For both of these processes, receptors on the cell surface allow cells to send and receive signals with cells in other parts of the body, to bring in required fuel, control growth and movement, and a number of other vital functions.
Throughout the body, there are numerous “systems” comprised of receptors and their ligands, which are the compounds that interact with receptors to activate, suppress, or cause some other response. Ligands can be produced by the body itself, or found in plant compounds, or synthesized in a lab, like many drugs – but they won’t have any effect unless they are able to interact with an existing receptor.
The Endocannabinoid System
Like any receptor system, the endocannabinoid system (ECS) is comprised of cannabinoid receptors and endocannabinoids, which are produced by the body and “designed” to fit exactly into the receptors, like a lock and key. Cannabinoid receptors also interact with exogenous ligands, both phytocannabinoids, which are found in plants, and synthetic cannabinoids, which are synthesized in a lab. These exogenous cannabinoids may have different or stronger effects on the receptors than endogenous cannabinoids do, but ultimately they are working with the same locks.
Two types of cannabinoid receptors are currently known, termed CB1 and CB2, as well as an orphan receptor, GPR55, which may be a third. All three are transmembrane receptors, which mean they can send a signal from outside of the cell into it. They are found in different concentrations in different tissues, and are known to interact differently with specific cannabinoids. For example, CB1 receptors are found in high concentrations in the brain and central nervous system, as well as in a number of organs (see Figure). CB2 receptors, on the other hand, are found largely in immune cells, as well as peripheral nerve, skin, and bone cells.
The ECS has a fairly unique function in the body. In many ways, it serves to regulate homestasis, by modulating the release of other neurotransmitters, which may be excitatory or inhibitory. Besides its own ligands, the ECS interacts with most of the major neurotransmitters including acetylcholine, dopamine, GABA, histamine, serotonin, glutamate, norepinephrine, prostaglandins, and opioid compounds. The specific action of different cannabinoids (both endogenous, phyto, and synthetic) can be explained by their differential action on receptor subtypes. For example, activation of receptors in the gastrointestinal system may cause increased appetite, while suppression of those receptors would cause decrease in appetite. Similarly, different cannabinoids cause different effects on the CB2 receptors found in the immune system, which is why some activate the immune system and others suppress it.
The widespread locations and interactions of the ECS causes both tremendous potential as well as challenge. Cannabinoids have shown promise in a broad range of diseases, reflecting the presence of cannabinoid receptors in every organ system and almost every tissue in the body, and many more are likely to be elucidated as the science advances. By tailoring cannabinoid therapeutics to target only specific receptor subtypes, more targeted effects are feasible. This type of approach is near impossible when using plant-based extracts, as the concentration and purity of the cannabinoid composition is highly variable. With advances in semi-synthetic methods, we are able to create highly purified, highly specific cannabinoids and combine them at optimal ratios to achieve the desired effects.