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Science
17 April 2026
9 min read

The Endocannabinoid System Across Species

What a veterinary surgeon knows about the biology of CBD.

When I explain CBD to clients, I usually start with the same sentence: every mammal you have ever known — yourself, your dog, your cat, the horse in the field next door — possesses the same fundamental biological network that makes CBD work. It's called the endocannabinoid system. It's ancient. It's universal. And it's the reason a compound extracted from a plant can have biological effects in such diverse animals.

This article is about that system. It's more technical than some of what we write, but understanding it properly is the difference between thinking of CBD as a mysterious wellness trend and understanding it as a well-characterised biological mechanism.

What the endocannabinoid system actually is

The endocannabinoid system (ECS) is a regulatory network of receptors, signalling molecules, and enzymes found throughout the body. It was discovered in the 1990s, largely as a consequence of researchers trying to understand how THC — the psychoactive compound in cannabis — exerted its effects. The system was named after cannabis because that's how we found it, not because it has anything inherently to do with the plant.

The ECS has three main components:

Receptors: CB1 (primarily in the central nervous system, gut, and some immune cells) and CB2 (primarily in immune cells, peripheral nervous system, and various tissues).

Endocannabinoids: Signalling molecules produced by the body itself. The two main ones are anandamide (from the Sanskrit "ananda," meaning bliss) and 2-arachidonoylglycerol (2-AG).

Enzymes: FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase) break down endocannabinoids after they've done their job.

The ECS doesn't have a single function. It modulates pain signalling, inflammatory responses, mood, appetite, sleep, memory, immune function, and cellular stress responses. It acts as a rheostat — a fine-tuning system that keeps other biological systems in balance.

Where the species differences matter

Here's where a veterinary perspective is useful. The ECS is conserved across all mammals — but not identical. There are meaningful species differences that pet owners and even some human wellness writers tend to miss.

Dogs: Dogs have an unusually high density of CB1 receptors in the cerebellum and brainstem. This has clinical implications — dogs are particularly susceptible to THC toxicity, which is why accidental cannabis ingestion is a veterinary emergency in canines. For CBD specifically (which does not bind CB1 directly), this density matters less, but it explains why veterinary CBD protocols are typically conservative.
Cats: Cats have a somewhat different ECS distribution, but more importantly, they have unusual drug metabolism. Cats are deficient in glucuronidation — a liver pathway that processes many drugs — which means many compounds that are safe in dogs are toxic in cats. CBD metabolism in cats is still being characterised, but there is reason for caution. This is why a competent vet will not apply canine protocols to feline patients.
Horses: Horses have a well-developed ECS, particularly in the gut and musculoskeletal system. There is growing interest in equine CBD for inflammatory conditions, but dosing is complicated by horses' large size and unique pharmacokinetics.
Humans: The most extensively studied ECS, though still not fully characterised. Humans have roughly comparable receptor distribution to other mammals, but individual genetic variation (including in the FAAH enzyme) creates significant variability in response.

How CBD interacts with the system

Here's a point that even some wellness brands get wrong: CBD does not bind strongly to CB1 or CB2 receptors. That's not how it works.

Instead, CBD is what pharmacologists call an "allosteric modulator" — it changes the shape of the receptor in a way that affects how other molecules (including the body's own endocannabinoids) bind to it. It also inhibits FAAH, which means the body's own anandamide persists longer before being broken down. And it interacts with several non-cannabinoid receptors — including the serotonin 5-HT1A receptor, TRPV1 (involved in pain and inflammation), and PPAR-gamma (involved in inflammation and metabolism).

This multi-target action is part of why CBD is hard to study with traditional pharmacological methods. Most drugs have a single, clearly-defined mechanism. CBD has several, which is also why the "entourage effect" — the synergistic action of CBD with other plant compounds — is thought to be significant.

The clinical evidence

I want to be careful here, because this is where a lot of CBD writing gets sloppy. The evidence base varies enormously depending on what condition you're asking about.

Where the regulators have spoken: The MHRA licences a CBD-based prescription medicine (Epidyolex) for specific, narrow indications. That decision was based on randomised controlled trials. A licensed medicine is a different category from a food supplement, and the two regulatory routes should not be confused.
Where the published research is active: Peer-reviewed studies are looking at how the endocannabinoid system interacts with sleep, mood, pain signalling and inflammatory tone — and at how cannabinoids modulate it. The trial base is heterogeneous and the conclusions are not settled.
Where claims regularly outrun the evidence: Marketing language in the consumer CBD market frequently goes far beyond what the published research supports. As a clinician, I won't make claims I can't stand behind, and Aponia makes none for its product. Aponia is a food supplement; it is not a treatment for any condition.

Why this matters for how we formulate

Understanding the ECS shapes how we think about CBD formulation. A few specific decisions that follow from the science:

Full spectrum over isolate. The endocannabinoid system has multiple receptor targets, and minor cannabinoids (CBG, CBC, CBN) and terpenes interact with it alongside CBD itself. A full-spectrum extract preserves more of the plant's natural profile than an isolate. We don't make a claim about clinical outcomes from this — only that we prefer the more complete starting material.
Hemp seed carrier oil, not MCT. Because cannabinoids are fat-soluble, they need a lipid carrier. Hemp seed oil naturally contains fatty acids that complement the plant extract and provide their own omega-3 and omega-6 benefits. MCT coconut oil is cheaper and shelf-stable, but it's a purely commercial choice — not a pharmacological one.
Sublingual administration. The oral mucosa allows direct absorption into the bloodstream, bypassing first-pass metabolism in the liver. This gives better bioavailability than swallowed CBD, which loses significant potency in the digestive tract.
Consistent, measurable dosing. Because individual response varies (including genetically), consistency matters more than escalating dose. A graduated dropper is not a gimmick — it's the only way to dose reproducibly.

The short version

The endocannabinoid system is real, it's biologically fundamental, and it's the reason CBD has effects at all. It's also the reason those effects vary across species and individuals. Understanding it properly is what separates a well-designed CBD product from a fashionable one.

If you have specific questions about CBD in a species I haven't covered, or about a particular clinical scenario, email me. It's genuinely the kind of thing I find interesting to discuss.

Alastair Greenway MRCVS

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