The endocannabinoid system: how the body talks to cannabinoids

The research, explained: what the studies actually say.

The endocannabinoid system comes up everywhere once the conversation turns to CBD and cannabis. Yet it is a system no one teaches at school, and one that science itself only discovered a few decades ago. In this article we try to explain it properly: what it is, how it works, and what the research really says about the way it talks to the plant’s cannabinoids.

We do it with the angle of our “The research” series: we report what the studies indicate, with links to dig deeper, without promising results. You will find a reminder on this point at the end of the article.

The system they don’t teach at school

The endocannabinoid system, often shortened to ECS, is a signalling network present across much of the body: the nervous system, the immune system, the digestive tract and more. It was only identified from the 1990s onwards, while researchers were trying to understand how cannabis produced its effects.

Out of that question came a discovery bigger than the plant itself: the body has a regulatory system that uses molecules similar to cannabinoids. A review published in Cells describes it as one of the main systems that help maintain homeostasis, the body’s internal balance (Lowe et al., 2021). It is also why it comes up so much in the CBD world: to understand the plant, you first have to understand this system.

How it’s built: receptors, endocannabinoids, enzymes

The ECS has three main components, and understanding them makes everything else clearer.

The receptors. They are the “antennas” that receive the signal. The two main ones are CB1, concentrated above all in the central nervous system, in brain areas linked to memory, emotions and cognition, and CB2, more present in immune cells, where it helps regulate inflammatory responses.

The endocannabinoids. They are the molecules the body makes itself to activate those receptors. The two most studied are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They have different affinities for the receptors: anandamide acts mainly on CB1, while 2-AG works on both.

The enzymes. They are the maintenance system: they produce endocannabinoids when needed and break them down once their job is done, so the signal stays on only as long as necessary.

These three elements, receptors, endocannabinoids and enzymes, are described as the backbone of the system in numerous scientific reviews (Cells, 2024).

Homeostasis: the system’s real job

If there is one idea to take home, it is this: the ECS’s underlying job is to keep balance. It works like a regulator that, when a function tips out of balance, steps in to bring it back to the right point.

Research links the activity of this system to the regulation of everyday processes such as the stress response, sleep, appetite, memory and the immune response. It is important to read that sentence for what it is: research indicates that the system takes part in regulating these functions. It does not mean that a cannabinoid-based product “does” something to them. It is a distinction we always keep in mind, and it is at the heart of this series.

How phytocannabinoids interact

This is where the plant comes in. The cannabinoids in hemp, called phytocannabinoids, interact with this system, but in different ways.

THC acts directly: it binds to CB1 receptors almost like a key in its lock, and that is where its psychoactive effects come from.

CBD works in a more indirect and therefore subtler way. Studies describe several mechanisms: it acts as a negative allosteric modulator of the CB1 receptor, meaning it does not “switch it on” but changes its behaviour (Laprairie et al., 2015, British Journal of Pharmacology); and it interferes with the enzyme that breaks down anandamide, helping to raise its levels, as well as acting on other targets beyond the ECS in the strict sense (Almeida et al., 2020, Pharmacology Research & Perspectives). In simple terms: CBD does not force the system, it influences it gently.

It is also why a full extract, in which several cannabinoids and terpenes coexist, is of research interest compared with a single isolated molecule. If you want to see how this plays out in our work in the field, we tell the story in our article on how hemp is grown naturally.

The “endocannabinoid tone”: an interesting idea

An emerging concept is that of endocannabinoid tone: the overall state of the system, that is, how many endocannabinoids are in circulation, what condition the receptors are in, and how well the whole thing works. Research suggests this tone is not fixed, but can be influenced by lifestyle.

For example, some studies indicate that aerobic exercise is associated with an increase in circulating endocannabinoids, and that the omega-3 fatty acids in the diet are precursors of these molecules (McPartland et al., 2014, PLOS ONE). It is still an evolving area, but it conveys the idea of a living system, in constant dialogue with how we live, move and eat.

In short

The endocannabinoid system is the network the body uses to keep itself in balance, made of receptors, endocannabinoids and enzymes. The cannabinoids in hemp interact with this network, each in their own way, and that is where all the scientific interest in the plant comes from. Understanding the system, before the product, is the most honest way to find your bearings.

For a clear, accessible overview, a good reference source is Project CBD, which collects and explains the studies on the subject.

If instead you want to start from the plant where all this begins, take a look at our CBD flower collection and our range of oils, grown with the method we describe in our Manifesto.

Informational content, it does not replace medical advice. The cited studies describe mechanisms and observations from scientific research and do not constitute therapeutic claims or promises of results.