Liposomal CBD oil:
the endocannabinoid system in dogs, cats and horses
How does the endocannabinoid system work in dogs and cats, through which receptors does CBD modulate pain, anxiety, and inflammation, and what does the most recent veterinary literature say about its clinical application? Substantiated with peer-reviewed studies.
By Stefan Veenstra DVM
The endocannabinoid system: a fundamental regulatory system
The endocannabinoid system, abbreviated ECS, is present in all vertebrates. It is one of the oldest signaling systems in the animal kingdom. The system consists of three parts: the body’s own cannabinoids (anandamide and 2-AG), receptors (CB1 and CB2) and enzymes that break down the body’s own cannabinoids after use. [1]
CB1 receptors are mainly found in the brain and central nervous system. They regulate how nerve cells communicate with each other. CB2 receptors are mainly found in immune cells and organs outside the brain. They control inflammation and pain responses. CBD does not act directly on these receptors but indirectly affects them and also activates other receptors, including those for pain and serotonin. [2]
Dogs, cats, and horses each react differently to CBD
The ECS is present in all three, but the distribution and density of the CB1 and CB2 receptors varies from species to species. This has direct consequences for how you dose and what you can expect.
Dog: extra sensitive, low starting dose
Dogs have more CB1 receptors in the posterior part of the brain than humans, particularly in the cerebellum. The cerebellum regulates coordination and balance. This higher receptor density makes dogs more sensitive to cannabinoids than humans.
This is very visible with THC: dogs can no longer stand up with small amounts of THC. This is called static ataxia. CBD works through a different route than THC and is much safer, but the increased sensitivity also applies here. In dogs, always start with the lowest possible dose and build up slowly. The margins are narrower than in humans.
Cat: works well, but liver processes more slowly
Cats have fewer CB1 receptors in the brain than dogs, but relatively many CB2 receptors in immune cells. This makes CBD particularly useful in cats for inflammation and immune problems.
The point of attention in cats is the liver. Cats lack a liver enzyme that breaks down many substances, including CBD. As a result, CBD stays in the body longer in cats than in dogs. The dose should be lower and you give it less often. Also, don’t use full-spectrum CBD with a lot of terpenes in cats: certain compounds in it are more difficult for cats to process.
Horse: ECS also present in the intestine, joints and nervous system
In horses, CB1 and CB2 receptors have been shown to be present in the intestinal wall, joints, and pain nervous system in recent years. This provides a biological basis for the use of CBD for pain, inflammation and stress in horses.
Studies show that CBD lowers cortisol in horses during transport. There is also a documented case of reduction in crib bites. Research at the Freie Universität Berlin (2023) showed that oral CBD in ponies is easily absorbed and produces similar effects as in other animal species. Sport horses: CBD is on the USEF doping list. Check the rules around competitions.
| Species | CB1 density | CB2 Profile | Practical point of attention |
|---|---|---|---|
| Dog | High in cerebellum and brainstem | Widely present in immune cells and peripheral tissue | Close therapeutic width. Start low, build up slowly. Strictly avoid THC. |
| Cat | Lower than dog | Relatively high in immune cells, strong anti-inflammatory profile | Limited glucuronidation. Lower dose, longer intervals. No phenolic terpenes. |
| Horse | Present in CNS, dorsal root ganglion, intestinal nervous system | Demonstrated in intestinal wall, immune cells and joint tissue | Orally absorbable. Relevant indications: joint pain, transport stress, stereotypical behavior. |
NGD Care Behavioral Protocol: CBD for Anxiolytic and Stress Modulation
NGD Care Joint Protocol: CBD and PEA Synergy for Joint Pain
NGD Care Skin Protocol: CBD for Atopic Dermatitis
How does CBD work exactly?
CBD is not psychoactive. It doesn’t intoxicate, nor does it bind directly to the CB1 and CB2 receptors like THC does. CBD works more subtly: it affects multiple receptor systems at the same time, indirectly and complementarily. [3]
It inhibits the enzyme that breaks down anandamide, allowing the body to retain more of its own “happiness chemical.” It activates serotonin receptors, which reduces anxiety. It dampens pain receptors in the nervous system. And it inhibits inflammatory pathways via receptors in immune cells. This broad profile explains why CBD works for such a wide range of complaints: joint pain, anxiety, epilepsy, skin problems and inflammation. It’s not one truck. There are four at the same time. [4]
Full-spectrum extract: why the whole does more than the sum of its parts
NGD Care CBD oil is a full-spectrum extract. That means that in addition to CBD, it also contains other cannabinoids such as CBG, CBC, and CBN, plus terpenes. These substances reinforce each other’s effect. This is called the entourage effect. [5]
CBG has an immediate pain and anti-inflammatory effect and inhibits the reuptake of serotonin and GABA. CBC modulates pain ducts. Terpenes such as linalool and beta-caryophyllene also have anxiolytic and anti-inflammatory properties of their own. A study in PMC (2024) with full-spectrum hemp oil in dogs with pain showed effective pain reduction, increased activity, and good tolerance after 8 weeks. [6]
Liposomal formulation: bioavailability in a fat-soluble substance
CBD and other cannabinoids are highly lipophilic and poorly water-soluble. Oral bioavailability of conventional CBD oil varies widely between individuals due to dependence on fat digestion and absorption capacity. Liposomal encapsulation addresses this in a similar way to fat-soluble vitamins: phospholipid vesicles protect cannabinoids in the gastrointestinal tract and facilitate absorption via endocytosis independent of the conventional fat absorption pathway. This is particularly relevant in animals with pancreatitis, EPI or chronic intestinal problems where fat absorption is reduced.
Veterinary clinical evidence by indication area
Osteoarthritis and chronic pain
The most documented veterinary application of CBD is for osteoarthritis pain in dogs. Gamble et al. (2018) showed significant improvement in pain scores (Canine Brief Pain Inventory) and mobility after CBD supplementation in a randomized placebo-controlled trial in dogs with osteoarthritis, with no clinically relevant side effects. [7] Corsato Alvarenga et al. (2023) confirm this as the strongest veterinary clinical evidence for CBD in a specific indication.
Epilepsy and seizure modulation
McGrath et al. (2019) showed in a blinded RCT significant reduction in seizure frequency in epileptic dogs treated with CBD compared to placebo. This is the only full-fledged veterinary RCT for CBD in epilepsy and forms the basis for the increasing integration of CBD into multimodal epilepsy treatment in dogs in consultation with neurologists. [8]
Fear and behavior
The anxiolytic action of CBD via 5-HT1A activation is mechanistically well-founded. Veterinary clinical studies in anxiety in dogs are still limited but promising. CBD works synergistically with PEA via the endocannabinoid system (entourage effect) and complements L-theanine and magnesium in Relax Support via the serotonergic system. In the Behavioral Protocol, CBD forms the endocannabinoid modulation component that complements the other anxiolytic supplements.
Atopic dermatitis and skin inflammation
CB2 receptors and TRPV1 channels are present in skin cells, keratinocytes, and mast cells. CBD modulates mast cell degranulation and the neurogenic inflammation that contributes to itching and skin irritation in atopic dermatitis. Clinical studies in dogs with atopic dermatitis show improvement in itch scores and skin condition after CBD treatment. [3]
CBD and PEA (palmitoylethanolamide) work synergistically through the endocannabinoid system. PEA inhibits FAAH indirectly via PPAR-alpha, which increases anandamide levels. CBD directly inhibits FAAH and indirectly modulates CB1/CB2. Together they reinforce each other’s effect via the so-called “entourage of body protection” mechanism. In the Joint Protocol, both are included as complementary pain and inflammation modulators via the ECS.
CBD and adaptogens (Adaptogen Complex: ashwagandha and rhodiola) have a complementary effect on chronic stress and anxiety. CBD modulates the acute stress response via 5-HT1A activation and CB1 inhibition of the amygdalar fear response. Adaptogens normalize chronic HPA axis dysregulation via NF-kB inhibition (ashwagandha) and serotonergic modulation (rhodiola). CBD acts quickly at the acute level, adaptogens at the structural level. The combination thus covers both the acute and chronic component of stress-related behaviour in dogs and cats.
Relax Support (L-theanine, magnesium, tryptophan) works through the GABA-ergic system and the serotonin-glutamate balance, in addition to the endocannabinoid system of CBD. L-theanine increases GABA and decreases glutamate. CBD modulates via 5-HT1A and CB1. Magnesium modulates NMDA receptors involved in chronic stress response. The three supplements have no overlapping mechanisms but act on additional anxiety and stress levels. In the Behavioral Protocol , CBD, Adaptogen Complex and Relax Support together form the complete neurobiological anxiolytic component.
Oncology: quality of life, appetite and anti-tumor properties
In dogs and cats with cancer, CBD is not a primary treatment but a valuable addition to the regular oncological treatment plan. The ECS plays a role in the regulation of metabolism, appetite, and gut health, and is densely populated with receptors and enzymes in the gut wall that play a role in the response to chemo-related nausea and appetite loss.
Cancer-induced cachexia is a serious and fatal metabolic disorder in which muscle and fat tissue is excessively broken down. CBD can partially counteract these side effects through appetite stimulation and anti-emetic effects. Cannabinoids, particularly CBG in full-spectrum formulations, have demonstrated appetite-stimulating effects in animal studies. CBD itself has an antiemetic profile via 5-HT1A activation and indirect CB1 modulation that reduces nausea and vomiting after chemotherapy.
Studies show that CBD combined with cytotoxic agents increases drug uptake and potentiates cytotoxic activity in human glioma cells. The anti-proliferative and pro-apoptotic effects of CBD have been described in multiple tumor cell lines but have not yet been confirmed in double-blind studies. This currently places CBD in oncology in the category of promising supportive supplement for quality of life, not as a replacement for proven oncological treatment.
Systematic review · Front Vet Sci 2026 · CBD and canine oncology
The review described the potential anti-tumor effect of CBD in dogs via modulation of the tumor microenvironment, EGFR signal inhibition, and pro-apoptotic mechanisms. The authors concluded that CBD is a promising anti-cancer agent based on the existing evidence.
Dosage and caution per animal species
Dog: high CB1 density in cerebellum and brainstem makes the therapeutic width narrow. Always start with the lowest recommended dose and build up over 2-4 weeks. At doses that are too high, sedation, ataxia and paradoxical appetite loss may occur. Strictly avoid THC. CBD can prolong the metabolization of other medications via CYP450 enzyme inhibition.
Cat: Limited glucuronidation calls for lower doses and longer dosing intervals than in dogs. Only use CBD products specifically formulated for cats, without added phenolic terpenes. In cats with liver disease, be extra careful because of reduced first-pass metabolization.
Horse: oral CBD is easily absorbed, but pharmacokinetics differ due to body size and intestinal transit time. Sport horses: CBD is on the USEF doping list, use with caution around competitions. Therapeutically promising for joint pain, transport stress and stereotypical behavior. Always in consultation with an equine vet.
Scope of application CBD oil: dog, cat and horse
Osteoarthritis and chronic joint pain as an adjunct to or alternative to NSAIDs. Anxiety, overstimulation and stress-related behavior, in synergy with Adaptogen Complex and Relax Support. Epilepsy and seizure modulation in consultation with a veterinarian. Atopic dermatitis and skin inflammation. Appetite stimulation in illness, recovery and oncology. Nausea and antiemetic support in chemotherapy. Oncological quality-of-life support. Neuropathic pain. Horse: joint pain, transport stress, stereotypical behavior. Always in consultation with an (integrative) veterinarian, especially in the case of epilepsy, oncology and concomitant medication use.
Conclusion
The ECS is a fundamental regulatory system in dogs, cats, and horses that coordinates pain, anxiety, inflammation, mood, appetite, and metabolic homeostasis. CBD modulates this system via a broad receptor profile that conventional pharmacological agents cannot match. The species-specific CB1/CB2 density differences determine the dosing profile per animal species and require a species-appropriate approach.
The synergy of CBD with PEA (ECS entourage), Adaptogen Complex (HPA axis) and Relax Support (GABA-ergic pathway) makes it a central component in the Behavioral Protocol for broad anxiolysis at multiple neurobiological levels simultaneously.
In oncology patients, CBD provides valuable quality of life support through appetite stimulation, antiemetic action and pain modulation, in addition to regular treatment. Its anti-tumor properties are promising but still require controlled veterinary evaluation before clinical recommendations are possible.
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Literature
- Maccarrone M, Bab I, Biro T, et al. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci. 2015; 36(5):277-296.
- Tuesta LM, Zhang Y. Mechanisms of cannabis and cannabinoid contributions to drug seeking and relapse. Trends Neurosci. 2014; 37(5):277-286. [CB1 and CB2 Receptor Biology and Distribution in Mammals]
- Freundt-Revilla J, et al. The clinical use of cannabidiol and cannabidiolic acid-rich hemp in veterinary medicine and lessons from human medicine. J Am Vet Med Assoc. 2023; 261(5). doi:10.2460/javma.23.02.0064. [Veterinary CBD Review Including ECS, Mechanisms, Seizure, OA Atopy 2023]
- Corsato Alvarenga I, Panickar KS, Hess H, McGrath S. Scientific validation of cannabidiol for management of dog and cat diseases. Annu Rev Anim Biosci. 2023;11:227-246. [Most Authoritative Veterinary CBD Review, Annual Reviews 2023]
- Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011; 163(7):1344-1364. [Entourage Effect Full-Spectrum Extract]
- Efficacy and tolerability of full spectrum hemp oil in dogs living with pain. PMC. 2024. PMCID: PMC11272626. [8-Week Clinical Study Full-Spectrum Hemp Oil in Dogs with Pain 2024]
- Gamble LJ, Boesch JM, Frye CW, et al. Pharmacokinetics, safety, and clinical efficacy of cannabidiol treatment in osteoarthritic dogs. Front Vet Sci. 2018;5:165.
- McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL. Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. J Am Vet Med Assoc. 2019; 254(11):1301-1308.
- Miagkoff L, Girard C, St-Jean G, et al. Cannabinoid-related receptors in sensory neurons of the equine dorsal root ganglion. Front Vet Sci. 2023;9:1050884.
- Pharmacokinetics of cannabidiol and its two main phase I metabolites in Connemara ponies. Front Vet Sci. 2025. doi:10.3389/fvets.2025.1599934.
- Cunha RZ, et al. The use of cannabidiol as a novel treatment for oral stereotypic behavior (crib-biting) in a horse. Fat Anim Sci. 2023;19:100289.
- Anti-tumoral effect of CBD in canine oncology: systematic review. Front Vet Sci. 2026. doi:10.3389/fvets.2026.1800410.
- Moreno-Lopez N, et al. Cannabis-based products for medicinal use in dogs and cats: a systematic review. J Small Anim Pract. 2025;66:855-870.
This information is educational in nature and based on available scientific literature. The studies mentioned are not always directly applicable to the specific formulation described here. This text does not replace a veterinary consultation and does not contain any therapeutic claims. The legal status of CBD products varies by country and region. Always consult a veterinarian when using for serious or complex conditions and when taking other medication at the same time