What is the endocannabinoid system?

The endocannabinoid system (ECS) was described for the first time in the 1990s, building on the work of Raphael Mechoulam's team (the Israeli chemist who had identified THC in 1964) and of Lisa Matsuda (who cloned the CB1 receptor in 1990).

It was while trying to understand how THC produces its effects on the body that researchers identified the cannabinoid receptors in the human brain, and then the endogenous molecules (produced by the body) that bind to them — the endocannabinoids.

The endocannabinoid system comprises three main elements.

The receptors

Two main receptors have been identified:

• CB1: found mostly in the central nervous system (brain, spinal cord), at particularly high concentrations in the cortex, the hippocampus, the cerebellum and the basal ganglia. A few CB1 receptors are also present in the periphery (gut, liver, adipose tissue).
• CB2: found mostly in the immune system (spleen, thymus, tonsils, circulating immune cells) and certain peripheral cells.

Other receptors are also modulated by cannabinoids, among them the nuclear receptors PPAR-γ, TRPV1 (the vanilloid channel, linked to pain and temperature) and GPR55.

The endogenous ligands (endocannabinoids)

The body produces its own cannabinoid molecules:

• Anandamide (AEA): isolated in 1992, its name derives from the Sanskrit ananda ("blissful joy"). Short half-life.
• 2-AG (2-arachidonoylglycerol): isolated in 1995, more abundant than anandamide in the brain.

These endocannabinoids are synthesised on demand from membrane lipid precursors, act locally, and are then rapidly broken down by specific enzymes (FAAH for anandamide, MAGL for 2-AG).

The synthesis and degradation enzymes

The ECS works as a closed loop: production on demand, brief action, rapid degradation. The enzymes FAAH and MAGL are therapeutic targets explored by pharmaceutical research as a way of modulating the ECS indirectly without administering an external cannabinoid.

The ECS is today described as a global modulating system involved in regulating several major functions:

• mood regulation and the stress response;
• the sleep-wake cycle;
• appetite and energy metabolism;
• pain perception;
• memory and learning;
• immune response and inflammation;
• neuronal development (prenatal in particular).

This multiplicity of targets explains the sustained scientific interest in the ECS over 30 years, but also the difficulty of modulating it therapeutically without multiple side effects.

Phytocannabinoids (cannabinoids produced by plants) mimic the action of endocannabinoids by binding to the same receptors or by modulating their activity:

• THC is a partial agonist of the CB1 and CB2 receptors. Its affinity for cerebral CB1 explains its intoxicating effect.
• CBD has a low affinity for CB1 and CB2 and is not intoxicating. It acts mainly through indirect modulation: inhibiting the breakdown of anandamide (via FAAH), modulating the effect of THC on CB1, interacting with other receptors (TRPV1, PPAR-γ, serotonergic 5-HT1A).
• CBG and CBC have interaction profiles that are still poorly characterised clinically.

This diversity of actions is one of the reasons why the EFSA considers the available data **insufficient** to validate a health claim for CBD: the mechanisms are multiple, only partly understood, and their clinical translation has yet to be demonstrated in controlled trials. For a detailed review of these questions, see Di Marzo, *Nature Reviews Drug Discovery*, 2018.

On many CBD brand websites, the endocannabinoid system is presented as proof of efficacy: "CBD supports your ECS", "CBD restores the balance of your ECS", "the ECS influences everything, so CBD helps everything".

These formulations rest on a problematic scientific shortcut. The existence of a target biological system does not mean that a molecule which modulates it produces measurable clinical benefits. The French and European authorities ([ANSM](https://ansm.sante.fr/dossiers-thematiques/cannabis-a-usage-medical), EFSA) have recognised no health claim tied to the CBD-ECS interaction. The French framework arising from the Conseil d'État ruling of 29 December 2022 permits the sale of wellness CBD, without thereby granting it the status of a health product.

The only cannabinoid-based medicine fully authorised in France is Epidyolex® (purified CBD) for certain rare childhood epilepsies — dispensed on hospital prescription, not in shops.

• The ECS is a network of receptors (CB1, CB2) and endogenous molecules (anandamide, 2-AG) discovered in the 1990s.
• It is involved in regulating sleep, mood, pain, appetite and immunity.
• CBD modulates the ECS indirectly, with no intoxicating effect.
• No health claim tied to the CBD-ECS action is validated by the EFSA.
• The existence of a target system is not enough to demonstrate a clinical benefit.
• CBD is not a medicine. If you have any medical doubt, consult a healthcare professional.

Does everyone have an endocannabinoid system?

Yes. The ECS is present in all mammals and in several other vertebrates. Cats, dogs and horses also have CB1 and CB2 receptors, which explains the veterinary interest in cannabinoids (although no veterinary marketing authorisation exists in France to date).

Can the ECS be "dysfunctional"?

A research hypothesis known as "clinical endocannabinoid deficiency" (Russo, 2004) suggests that an underactive ECS could be involved in certain conditions (migraine, fibromyalgia, irritable bowel syndrome). This hypothesis remains debated and has not led to clinical recognition.

Does CBD "rebalance" the ECS?

That phrasing is marketing, not science. CBD modulates ECS activity through several indirect routes. There is no clinical measure of ECS "balance", and no authority recognises this claim.

Do sport or meditation activate the ECS?

Several studies suggest that physical exercise raises circulating endocannabinoid concentrations (anandamide in particular), which could explain the "runner's high". Meditation and certain mindfulness practices are also being studied in this context, without clinical validation as yet.

Do children have an ECS?

Yes. The ECS is active from prenatal life onwards and plays a role in neuronal development. That is precisely one of the reasons why any CBD product is not advised for minors, in the absence of data on the impact of external exposure on a developing ECS.

To explore our selection of CBD oils with a certificate of analysis, [browse our spectres-chimie catalogue](/categorie-produit/extracts-cbd). CBD is not a medicine. If you have any medical doubt, consult a healthcare professional.

• EFSA Journal 2026 — Update statement CBD novel food — primary
• ANSM — HHC classified as a narcotic, June 2023 — primary
• ANSM — New cannabinoids classified as narcotics, May 2024 — primary