By Francisca Javiera Medina Pontigo
A Veterinary Doctor with a Master's in Animal and Veterinary Sciences and a Doctorate in Forestry, Agricultural and Veterinary Sciences from the University of Chile.
Since 2016, she has been providing medicinal cannabis therapy to small animals and promoting the therapeutic uses of cannabinoids.
Since 2020, she has been conducting research at the University of Chile, mainly focused on evaluating the antitumoral properties of cannabinoids in canine cancer and developing new pharmaceutical formulations based on cannabinoids. She has published two articles in WOS journals on the use of CBD in veterinary oncology, as well as clinical case reports and review articles in veterinary journals.
She teaches undergraduate and postgraduate courses focused on the clinical use and pharmacology of cannabinoids and is currently a professor at Santo Tomas University (UST) and the University of the Americas (UDLA) in Chile. She has participated in multiple conferences and scientific outreach programmes dedicated to the use of cannabinoids in veterinary medicine.
Cancer in dogs and current treatments
Pets, such as dogs and cats, are increasingly considered members of the family. This has significantly improved the level of medical care they have access to. The longer life expectancy of dogs presents new challenges, as many chronic diseases can affect them, with cancer one of the most frequently diagnosed conditions. It is estimated that approximately one in four dogs develops some type of cancer during their lifetime, while in dogs older than 10 years cancer is the most common disease and the leading cause of death (1). Thus, dogs are the most studied species in veterinary oncology. Research includes genomic studies of tumours and the development of alternative and complementary drug therapies that overcome the limitations of available antitumoral drugs, limit resistance to chemotherapeutic agents and reduce their side effects (2).
The role of the endocannabinoid system in cancer
Since its discovery in 1993, the endocannabinoid system (ECS) has been investigated for its role in the body's balance (homeostasis) and the development of various diseases. This system is present in all vertebrates, including dogs, and is a target of human and veterinary medical research.
The ECS is composed of cannabinoids naturally generated by animals, the most abundant and researched being AEA (anandamide) and 2-AG (2-arachidonoylglycerol). These modulate type 1 (CB1) and type 2 (CB2) cannabinoid receptors, as well as other receptors, such as GPR55, TRPV and PPAR (3). The CB1 receptor is found primarily in the central and peripheral nervous system, while CB2 is located primarily in the immune system. In dogs, the presence of the ECS has been identified in the gastrointestinal tract, in the skin of healthy dogs and those with atopic dermatitis, in the central and peripheral nervous system, and in joints (4–9), participating in antioxidant, anti-inflammatory and analgesic functions, among others, and intervening in the replication of cancer cells (10).
Higher levels of AEA and 2-AG have been observed in the cells of various human cancers (pituitary adenoma, colorectal carcinoma, prostate carcinoma, endometrial sarcoma, and glioma) than in healthy tissues. Similarly, the number of CB1 and CB2 receptors can vary in different types of cancer, and these levels have been associated with favourable or unfavourable prognoses, depending on the type of tumour (2,10).
In dogs, the levels of four endocannabinoids—AEA, 2-AG, oleoylethanolamide (OEA), and palmitoylethanolamide (PEA)—were compared in multicentric B-cell and T-cell lymphomas. The study revealed significantly higher levels of AEA, OEA, and PEA in the lymphoma groups than in healthy dogs. Conversely, 2-AG levels were higher in healthy dogs (10). Regarding receptor expression, it has been observed that CB1 and CB2 are present in high quantities in low-grade mast cell tumours, similar to healthy tissues. In contrast, in high-grade mast cell tumours, a lower amount of both receptors has been found, indicating a negative relationship between the aggressiveness of these cancers and the expression of cannabinoid receptors (2,11).
Most of the studies on the expression of CB1, CB2 and other ECS-associated receptors in tumour cells have been performed in humans. The relative scarcity of veterinary studies highlights the need to investigate ECS alterations in veterinary oncology and the possibility of modulating them using external cannabinoids, both in cell and animal models and in clinical studies.
Current research and therapeutics with cannabis in canine cancer
Phytocannabinoids have been proposed as possible external regulators of the ECS. The most abundant ones in the cannabis plant are delta-9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD). CBD lacks psychotropic capacity and has an affinity for various receptors, including CB1, CB2, GPR55, GPR119, TRPV and PPAR, in addition to neuroprotective, antiepileptic, anxiolytic, anti-inflammatory, analgesic and anticancer properties. THC has psychotropic capacities, but it has also been shown to have anti-inflammatory, analgesic, appetite-stimulating, antiemetic and muscle-relaxing properties. In safety studies in dogs, THC has been shown to be safe. It tends to produce a higher proportion of moderate to severe adverse effects than CBD, but fewer symptoms of liver overload (12). THC is a partial agonist of CB1 and CB2 and also acts on other receptors, such as GPR55 and TRPV1-5, influencing nociception, thermoregulation, salivary secretion, smooth muscle tone, heart rate, and calcium and magnesium homeostasis.
The study of the antitumoral capabilities of cannabinoids in dogs is recent, with research beginning in 2019, compared to studies in humans, which have been conducted since the early 2000s. According to the systematic review we conducted this year, 2026, at the University of Chile, the effect of CBD on canine cancer has been evaluated preclinically in urothelial carcinoma, glioma, lymphoma, mammary carcinoma, prostate carcinoma and osteosarcoma cells, with studies of isolated CBD, of extracts containing other cannabinoids in smaller proportions, and of combinations with chemotherapeutic drugs. Conversely, when it comes to THC there is only information on lymphoma and prostate carcinoma (13).
In dogs with high-grade lymphoma, the pharmacokinetics of doxorubicin administered in conjunction with CBD were studied, and it was observed that there are no variations compared to its administration without CBD. Furthermore, CBD was well tolerated as an adjunct to CHOP therapy (prednisone, vincristine, cyclophosphamide and doxorubicin), with no serious adverse events recorded (14). Preclinical studies in B-cell and T-cell lymphoma cell cultures have, on the other hand, evaluated the effects of THC and CBD. Better results were observed in reducing the proliferation of these cancer cells with isolated CBD and high CBD plant extracts than with THC and its synthetic analogue WIN 55-212-22 (15,16).
In breast cancer, there are only cellular studies, in which isolated CBD, in extract and delivered in nanoemulsion, has been tested. These studies have shown that, in its various forms, CBD decreases cell proliferation through mechanisms that involve cell cycle arrest and induction of cell death (apoptosis). It also reduces migration and invasion processes involved in metastasis (16,17).
Canine glioma has also been investigated through a cell study and another study on a mouse model that evaluated isolated CBD and CBD extract. In the cell study, isolated CBD showed better results in decreasing glioma cell proliferation than the high-CBD plant extract. In the mouse study isolated CBD was used, comparing it with radiotherapy and the combination of both therapies, observing better results with the combined treatment in the survival time of the mice (18,19).
To date, one study has been conducted on osteosarcoma using a cell model, in which isolated CBD, CBDA (precursor of CBD) and a CBD extract were compared. The best results in reducing the proliferation of tumour cells were observed with the CBD extract, while CBDA had the lowest score (16).
A study has also been published on canine prostate carcinoma, analysing THC and CBD extracts in cell cultures. This found better results in reducing the number of cells with the CBD extract than with the THC extract (20).
In canine urothelial carcinoma, the effect of isolated CBD, alone and combined with chemotherapeutic agents (mitoxantrone, vinblastine and carboplatin) or piroxicam was evaluated in a cell model. CBD as a monotherapy induced the death of these cancer cells. In combination therapies, it showed a synergistic effect with mitoxantrone and vinblastine; however, the combination with carboplatin produced antagonism, while the combination with piroxicam did not significantly affect these cells (21).
The 2021 study by Henry et al. also showed that CBD can have synergistic and antagonistic effects with various chemotherapeutic agents, such as doxorubicin and vincristine. In lymphoma, osteosarcoma, and mammary carcinoma cells in dogs, a synergistic effect with vincristine was observed at both low and high doses. With doxorubicin, the effect was synergistic only at high doses, while low doses showed antagonistic effects, decreasing the action of this chemotherapeutic agent on cancer cells (16).
Conclusions
The number of published studies on different types of cancer in dogs remains limited, and scaling up to clinical studies with canine patients presents several difficulties. One is that studies conducted with CBD and THC extracts do not clearly specify either the concentration or the type of cannabinoids and terpenes present, making it difficult to distinguish which cannabinoids or combinations of cannabinoids and terpenes are responsible for the observed effects. Another complication for future clinical studies lies in the concentrations that would need to be administered, since in pharmacokinetic studies in dogs the milligram doses used cause blood concentrations in the order of nanograms. These concentrations are much lower than those found to be effective in the reviewed studies (microgram concentrations), indicating that higher doses may be needed than those tested so far in safety studies in dogs. Therefore, more studies are needed to confirm the reproducibility of the results obtained so far to understand the effect of cannabinoids on cancer in dogs, as well as studies on other types of cancer in which cannabinoids have shown effects, such as lung or colorectal cancer. The above, combined with the lack of standardisation of formulations and the inconsistency of the results found, partly explain why there are currently no veterinary drugs based on cannabinoids.
I hope that these challenges will motivate more researchers to become interested in this emerging field so that, in the near future, cancer therapy with cannabinoids will become established as another alternative at the veterinary level.
References:
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