The endocannabinoid system and you

What should the term endocannabinoid system mean to you? Apart from being a bit of a tongue-twister, its principal purpose is >balance. The human body is one of the most complicated biological “machines” we know of – and any complex machinery needs supervision to keep functioning properly. In the case of our bodies, the endocannabinoid system (or ECS, for short) is that capable supervisor, and an integral part of understanding the effect CBD has on our bodies.

A brief history of the endocannabinoid system

Any basic biology lesson covers the core bodily systems: the nervous system, the digestive system, the reproductive system and so on. So, why is it most people haven't heard of the ECS before? The answer lies in its complex nature and the ongoing research into it. The ECS’ microscopic components are present within other important body systems, helping them maintain optimal function, making it difficult for both its structure and its function to be clearly identified. Also, as its name suggests, studying its function is fairly closely tied to cannabis research, which has been slow to unfold due to previous and existing legal restrictions.

But why is it called the "endocannabinoid system"? Well, its discovery was a bit of a roundabout process. In the 1940s, scientists started isolating certain compounds from the hemp plant (Cannabis sativa), called cannabinoids, and began studying their effects on the human body. Still, it was only in the early 90s that internal receptors were found to which these hemp-extracted cannabinoids could bind and determine a response, and so these were termed cannabinoid receptors.

Around the same time, it was discovered that our bodies internally produce their own cannabinoid substances, which were then termed endocannabinoids (internally-produced cannabinoids) to distinguish them from phytocannabinoids (plant-produced cannabinoids). The endocannabinoid system’s name, therefore, reflects its research heritage, even as its functions and effects are still being determined through current study.

It’s important to note that the ECS is still a relatively new research topic. Unlike most other systems in the human body, the ECS doesn’t have enough studies under its belt to guarantee scientific consensus. A lot of research is done in vitro (on cell cultures in laboratories); most of it is still done on mice; observations on humans are yet ongoing (it takes years to observe long-term effects) or focusing on the ECS’ reaction to substances, rather than its structure. This doesn’t mean our knowledge is limited  - merely that our understanding is an ever-evolving process, subject to change as our studies advance. Here is what science has uncovered so far.

The beginner's guide to the ECS

As a delicate and complex machine, the human body functions best within certain intervals for parameters like temperature, pressure, pH and more – a state of balance called homeostasis. This is a delicate balance to maintain, but one of the great regulators that helps do that is the endocannabinoid system.

The ECS doesn’t directly transmit messages throughout the body, as the nervous system does, but rather acts indirectly by stimulating or inhibiting the transmission of chemical messages throughout the nervous and immune systems (the way a sluice gate can be adjusted to let more or less water flow through). However, by being present throughout such vast structures as the nervous and immune systems, the ECS does have body-wide influence.

As a major regulator, the ECS needs to be able to receive and respond to the chemical messages within the body. In order to achieve this, the ECS is comprised of chemical receptors (the two main ones being termed CB1 and CB2), the endocannabinoids that bind to them (the best-known ones being anandamide and 2-AG), and the enzymes that recycle the endocannabinoids, synthesising and degrading them as needed (endocannabinoids can’t be active permanently, as any message needs to have a beginning and an end).

If we refer to the sluice gate analogy above, then the receptors are the control buttons on the gate, which can only be operated when they are turned on with specific keys; the endocannabinoids are the keys, and the enzymes are the key keepers. But, unlike the example of a gate, these controls can do more than simply open and close a passageway. They are more similar to the control panel of a smart home: they can have different effects, depending on what they interact with, and can even be programmed to have a longer-lasting effect. To complicate matters even more, more than one key can activate such a control panel - but we’ll only discuss the ones with the best “fit”, for now.

How does the ECS work?

The two main receptors, CB1 and CB2, are found throughout the body. CB1 receptors seem to be present primarily in the nervous system, while CB2 receptors have been found and studied primarily on immune system components; but the receptors have also been found in other peripheral tissues, such as the spleen, the reproductive, urinary and gastrointestinal tracts, the endocrine glands, the arteries and the heart. Broadly speaking, the endocannabinoid anandamide mostly (but not exclusively) activates CB1 receptors, while the endocannabinoid 2-AG activates both CB1 and CB2 receptors in equal measure.

The endocannabinoids produced by the body are lipophilic, meaning they're not soluble in water, but in lipids such as the cell membrane. In fact, most of the time they don’t even exist in their active form, but as building blocks that only come together when needed, and are degraded soon thereafter. On their own, they can’t circulate in the bloodstream, and their effect is limited to the cells where they’re produced and their immediate neighbours. Some research suggests that they can, in fact, be transported to further locations encased in “rafts” made up of the same enzymes that ultimately also serve to degrade the endocannabinoids.>

When a cell receives a message from outside or from a distant part of itself - a signal which can be electrical (a small current caused by neurons firing) or chemical - the ECS enzymes put together the building blocks that create endocannabinoids on the spot, right in the cell membrane. The endocannabinoid molecules then bind to their respective CB1 or CB2 receptors which, in turn, stimulate or inhibit other chemical processes.

For example, in the central nervous system, messages are relayed chemically through the space between neurons via substances called neurotransmitters; the longer such a neurotransmitter stays active, the stronger the message it conveys. Through endocannabinoids and their receptors on the neurons’ membranes, the ECS can determine how long these neurotransmitters are present and the intensity of their message. So, when a neuron keeps passing on the message “There’s still pain in this toe because it was stubbed earlier and now it’s inflamed,” the endocannabinoid anandamide can bind to a CB1 receptor which stops the neurotransmitter from acting, cutting that message short and helping to decrease the feeling of pain.

The ECS meets cannabidiol

As we mentioned, the endocannabinoid system owes its name and eventual discovery to the increasingly detailed observations on the effects that the Cannabis plant compounds have on the human body. Humans have been using hemp for both recreational and medicinal purposes across generations and cultures long before the structure of the first cannabinoids was properly described in the 1960s. Since then, it's been discovered that most mammals possess an ECS which responds to the presence of cannabinoids - be they synthetic, produced in the body or by the hemp plant.

Over 110 cannabinoids have been identified in the hemp plant so far. Most of these can bind to the receptors of the ECS; some bind more precisely or have a more potent effect than others. Many studies on the ECS are done using synthetic or plant-extracted cannabinoids, as they are far easier to obtain, measure and dose than the endocannabinoids. The hemp-extracted THC and CBD are the two most well-researched cannabinoids, as they have been determined to have a similar effect on ECS receptors as the body-produced endocannabinoids anandamide and 2-AG, respectively.  

CBD presents a few advantages.

    • It’s the most abundant cannabinoid in industrial hemp, making it easy to extract.
    • It doesn’t have a psychotropic effect, meaning it doesn’t “get you high” as THC does. This could be down to the lower affinity it has for the CB1 receptors in the brain (it takes about 30 times more CBD than THC to activate a CB1 receptor).
    • Research has shown that introducing CBD into the body slows down the action of FAAH, the enzyme that degrades anandamide, thus keeping it present for longer and helping increase its natural effect.
    • In 2017, the World Health Organization's Expert Committee on Drug Dependence analysed existing data and determined that “CBD is generally well tolerated with a good safety profile.” They further stated that, “In general, CBD has been found to have relatively low toxicity [and that] while the number of studies is limited, the evidence from well controlled human experimental research indicates that CBD is not associated with abuse potential.

It's also worth noting that, as the ECS responds to more than one plant-based cannabinoid, it’s been observed that introducing more than the pure extract of one cannabinoid tends to amplify its effects. This phenomenon, where an extract of several hemp compounds (cannabinoids, terpenes, flavonoids) act together to have a greater effect, is called the entourage effect

A quick recap

This is, by no means, an exhaustive article on the topic, but we know it can still be exhausting to go through it all. Here are a few main ideas you should take away from it.

  • The ECS is a body-wide regulator system, with the main purpose of maintaining balance within and between the nervous system, the immune system and the systems they control.
  • The ECS is made up of receptors that can trigger various effects at a cellular level, internally-produced endocannabinoids that activate these receptors, and enzymes that synthesize and degrade the endocannabinoids. The result is a very precise mechanism that acts when and as needed to modulate the various chemical and electrical messages being transmitted throughout the body.
  • The receptors of the ECS also respond to phytocannabinoids produced by the hemp plant, such as CBD, which can trigger effects similar to the endocannabinoids’ and support the ECS’ function.
  • Research into the ECS and cannabinoids is a relatively young field of study, with our understanding into their structure, function and relationship deepening and evolving constantly. While there may not yet be a worldwide scientific consensus on CBD effects and usage, several regulator bodies, such as the FDA and WHO, have classified CBD as relatively safe, with no psychotropic effects and with no known addiction potential.

We believe that a well-informed user is a happier user, so we encourage you to further your CBD-related education.


Links to scientific studies and resources on the ECS used in this article:

https://www.practicalpainmanagement.com/pain/other/glial-cell-activation-neuroinflammation-how-they-cause-centralized-pain - about activated glial cells

http://www.lipidhome.co.uk/lipids/simple/endocan/index.htm - details the chemical composition and function of endocannabinoids in a more accessible language, though it’s harder to pinpoint which cited sources lead to which specific claims

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892852/  - how CB2 receptors influence activated glial cells and may help treat neurodegenerative diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099582/ - discusses structure and function of CB receptors, with this article for reference on where CB receptors are located. Also discusses affinity of various phytocannabinoids for the two receptors

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454279/ - discusses the role of endocannabinoids in neural plasticity and explains the processes involved, including triggers and processes for endocannabinoid synthesis and enzymatic degradation in synapses

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932105/ - details on ECB receptors in glial cells, so there’s discussion of both types of receptors and their effects within the brain

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222489/ - role of cannabinoids in pain and inflammatory processes, their interactions with ECS receptors

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209363/ - details the role of the ECS in the central nervous system, as well as observations regarding its actions in certain types of disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931549/ - an in-depth look at the CB2 receptor and its functions in various contexts

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423248/ - an in-depth look at lipid rafts and how CBD intake is associated with an increase in anandamide levels