What is the endocannabinoid system
The endocannabinoid system (ECS) is a biological system present in all vertebrates — humans, dogs, cats and other mammals included. It consists of receptors distributed throughout the brain and body, molecules produced by the body that bind to those receptors, and enzymes that synthesise and break down those molecules. The ECS was identified in the early 1990s during research into how cannabinoids from the cannabis plant interact with the human body.
This article covers the three components of the ECS, how cannabinoids from hemp interact with the system, and why understanding the ECS is relevant to anyone using or considering cannabidiol (CBD) oil. This article describes the system’s biology — it does not make claims about what CBD oil does in the body for any individual.
The three components of the ECS
The endocannabinoid system has three main components: receptors, endocannabinoids and enzymes.
Receptors. Two primary receptors have been identified: CB1 and CB2. CB1 receptors are concentrated in the brain and central nervous system, though they also appear in the liver, lungs and kidneys. CB2 receptors are found primarily in the peripheral nervous system and immune cells. A third receptor, GPR55, is sometimes described as a third cannabinoid receptor, though its classification remains debated in the research literature. Cannabinoid receptors are G protein-coupled receptors — a large class of cellular signalling proteins that respond to external signals and produce an internal cellular response.
Endocannabinoids. “Endocannabinoid” means a cannabinoid produced inside the body — the prefix “endo” from the Greek for “within.” Two primary endocannabinoids have been well characterised: anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Anandamide takes its name from the Sanskrit word for bliss — it was one of the first endocannabinoids identified, in 1992. Both molecules are derived from fatty acids and act as signalling molecules, binding to cannabinoid receptors and triggering cellular responses. Unlike most neurotransmitters, endocannabinoids are synthesised on demand rather than stored and released.
Enzymes. Two enzymes handle endocannabinoid breakdown. FAAH (fatty acid amide hydrolase) degrades anandamide. MAGL (monoacylglycerol lipase) breaks down 2-AG. Once an endocannabinoid has completed its signalling function and bound to a receptor, these enzymes metabolise it to prevent continued activity. The speed of this enzymatic breakdown contributes to how briefly endocannabinoids act at any receptor site.
How the ECS works — retrograde signalling
The ECS operates differently from most neurotransmitter systems. Classical neurotransmission runs in one direction: a presynaptic neuron releases a transmitter, which crosses the synaptic gap and binds to receptors on the postsynaptic neuron. The ECS runs retrograde — backwards.
When a postsynaptic neuron fires, it produces endocannabinoids that travel backwards across the synapse and bind to CB1 receptors on the presynaptic neuron. This retrograde signalling allows the receiving neuron to send a message back to the sending neuron, modulating the signal it receives. The ECS acts as a feedback modulator — adjusting activity in response to the current state of the system rather than generating primary signals of its own.
This retrograde function is part of why the ECS is involved in such a broad range of physiological processes. By modulating activity rather than driving it, the system participates in regulating multiple systems without being the primary driver of any single one.
Where the ECS is active in the body
CB1 receptors are densely distributed in the brain — particularly in regions associated with memory, coordination, pain processing and mood — as well as the spinal cord and peripheral nerves. Their concentration in the brain is why cannabinoids that bind strongly to CB1 (including THC) produce psychoactive effects.
CB2 receptors are primarily found in immune cells: T cells, B cells, macrophages and natural killer cells, as well as in peripheral tissues including the spleen, tonsils and thymus. CB2 activation does not produce the psychoactive effects associated with CB1 stimulation.
Both receptor types also appear in the gastrointestinal tract, liver, bone and reproductive tissues, reflecting the ECS’s broad regulatory presence across systems.
How plant cannabinoids interact with the ECS
Cannabinoids from the cannabis plant — phytocannabinoids — interact with the ECS because their molecular structure is similar enough to endocannabinoids that they can bind to the same receptors.
Tetrahydrocannabinol (THC) binds directly and strongly to CB1 receptors. This strong CB1 binding is what produces THC’s psychoactive effects. THC also binds to CB2 receptors, though with lower affinity.
Cannabidiol (CBD) has a different interaction profile. CBD does not bind strongly to CB1 or CB2 receptors directly. Research has identified several other mechanisms through which CBD interacts with biological systems — including TRPV1 ion channels, serotonin receptors (5-HT1A) and indirect modulation of endocannabinoid levels through FAAH inhibition. The full picture of CBD’s mechanism of action is still an active area of pharmacological research.
Cannabigerol (CBG) and cannabinol (CBN) are two other phytocannabinoids with distinct interaction profiles. CBG shows affinity for both CB1 and CB2 receptors. CBN has low potency at CB1 and CB2 but interacts with several other receptor systems. The CBD vs CBG vs CBN comparison covers the differences between these three cannabinoids.
Why does this matter for CBD oil users
Understanding the ECS matters for CBD oil users for one reason above all: it explains why CBD oil is not a simple on/off medication with a predictable, uniform effect. The ECS is a regulatory system distributed across the entire body, with receptor densities that vary between individuals, are influenced by genetics and are altered by conditions and medications. Two people with identical body weight taking the same CBD oil at the same amount may have different experiences because their ECS expression — receptor density, endocannabinoid production, enzyme activity — differs.
This individual variability is not a product quality issue. It’s biology. It’s also why guidance on CBD oil consistently recommends starting with a low amount, observing over time and adjusting with healthcare professional input rather than expecting a defined, reproducible response. The onset time guide covers this variability in practical terms.
The ECS also explains why CBD’s effects — whatever they are for a given individual — develop over time with consistent daily use rather than appearing dramatically after a single dose. The system is modulated rather than switched on, and modulation takes time to produce observable changes in complex biological systems.
The ECS in animals
The endocannabinoid system is not unique to humans. All vertebrates possess an ECS, which is why cannabinoid products developed for humans are also studied in veterinary contexts. Dogs and cats have CB1 and CB2 receptors and produce their own endocannabinoids.
Dogs have a notably high CB1 receptor density in the cerebellum compared to humans — one of the factors behind their heightened sensitivity to THC. This species difference is clinically relevant when choosing between full spectrum (trace THC present) and broad spectrum (THC removed) CBD products for pets. The pet CBD oil in Australia article covers this and related considerations for pet owners. The dog CBD dosage guide covers practical measurement for canine serving sizes.
EU Labs products and the endocannabinoid system
EU Labs CBD, CBG and CBN oils deliver phytocannabinoids — compounds from hemp that interact with the same receptor systems as the body’s own endocannabinoids. The EU Labs CBD Oil 3000mg Full Spectrum provides cannabidiol alongside minor cannabinoids and terpenes in a full spectrum extract. The EU Labs CBG Oil 3000mg delivers cannabigerol, and the EU Labs CBN Oil 3000mg delivers cannabinol — each with a distinct interaction profile relative to the ECS.
All products in the range are available through the Stillroot shop, shipping to Sydney, Melbourne, Brisbane, Perth, Canberra, Geelong and all Australian locations.
Frequently asked questions
What does the endocannabinoid system do?
The ECS is a regulatory system present in all vertebrates. It consists of CB1 and CB2 receptors, endocannabinoids (AEA and 2-AG) produced by the body, and enzymes that synthesise and break them down. The ECS operates via retrograde signalling — modulating activity in other systems rather than generating primary signals. It is active in the brain, central and peripheral nervous system, immune cells and numerous organ systems.
What receptors does CBD bind to?
CBD does not bind strongly to CB1 or CB2 receptors directly. Its interaction with biological systems involves TRPV1 channels, serotonin receptors (5-HT1A), indirect modulation of endocannabinoid levels through FAAH inhibition and other mechanisms identified in pharmacological research. The full mechanism of CBD action is still actively studied.
Why do people respond to CBD differently?
Individual ECS expression varies — receptor density, endocannabinoid production and enzyme activity differ between people based on genetics, health status, age and other factors. This variability means two people taking identical CBD oil at the same amount may have different experiences. It is a feature of the biology, not a product inconsistency.
Do dogs and cats have an endocannabinoid system?
Yes. All vertebrates have an ECS. Dogs have a particularly high CB1 receptor density in the cerebellum relative to humans, making them more sensitive to THC. This is why pet-specific CBD products often use broad spectrum formulations with THC removed, and why veterinary guidance is important before starting a CBD routine with a pet.
When was the endocannabinoid system discovered?
CB1 receptors were identified in 1988 by Allyn Howlett and colleagues. The first endocannabinoid, anandamide, was isolated in 1992 by Raphael Mechoulam’s team — the same researcher who had identified and synthesised THC in the 1960s. The term “endocannabinoid system” emerged through the early 1990s as the receptor-ligand system became more fully characterised.
These products have not been evaluated by the TGA. They are not intended to diagnose, treat, cure, or prevent any disease. You must be 18+ to purchase. Please consult a healthcare professional before use.
