Use of medicinal cannabis in dogs with multicentric lymphoma: a report of two casesABSTRACT
Multicentric lymphoma is the most common hematopoietic neoplasia in dogs, with chemotherapy being the standard treatment. Medicinal cannabis, especially cannabidiol (CBD), has been studied as a complementary therapy to mitigate symptoms and adverse effects of chemotherapy. This study reports two cases of dogs with multicentric lymphoma treated for two months with chemotherapy and cannabis oil. Both received the cyclosphosphamide, doxorubicin, vincristine, and prednisolone (CHOP) protocol combined with full-spectrum 3% cannabis oil for 60 days. The results suggest that medicinal cannabis may have helped reduce side effects, particularly in modulating myelotoxicity, with variations in neutropenia between cases. Additionally, one of the dogs showed reduced thiobarbituric acid reactive substances (TBARS) levels, suggesting a possible antioxidant effect of CBD. These findings indicate that cannabis oil may be a promising adjunct therapeutic option in the treatment of multicentric lymphoma in dogs, aiding in the management of chemotherapy-related adverse effects. However, individual responses vary, highlighting the need for further studies to clarify the mechanisms involved and establish more effective therapeutic protocols. This research reinforces the potential of medicinal cannabis as an ally in veterinary oncology, expanding perspectives for new therapeutic approaches.
Keywords:
cannabis; cancer; lymphoma; neutropenia; adjunct therapy
RESUMO
O linfoma multicêntrico é a neoplasia hematopoiética mais comum em cães, sendo a quimioterapia o tratamento padrão. A Cannabis medicinal, especialmente o canabidiol (CBD), tem sido estudada como terapia complementar para mitigar sintomas e efeitos adversos da quimioterapia. Este estudo relata dois casos de cães com linfoma multicêntrico tratados, por dois meses, com quimioterapia e óleo de Cannabis. Ambos receberam o protocolo ciclofosfamida, doxorrubicina, vincristina e prednisolona (CHOP) associado ao óleo de Cannabis full spectrum 3% por 60 dias. Os resultados sugerem que a Cannabis medicinal pode ter auxiliado na redução dos efeitos colaterais, particularmente na modulação da mielotoxicidade, com variações na neutropenia entre os casos. Além disso, um dos cães apresentou redução nos níveis de substâncias reativas ao ácido tiobarbitúrico (TBARS), sugerindo um possível efeito antioxidante do CBD. Esses achados indicam que o óleo de cannabis pode ser um adjuvante terapêutico promissor no tratamento do linfoma multicêntrico em cães, ajudando no manejo dos efeitos adversos da quimioterapia. No entanto, as respostas individuais variam, destacando a necessidade de mais estudos para esclarecer os mecanismos envolvidos e estabelecer protocolos terapêuticos mais eficazes. A pesquisa reforça o potencial da Cannabis medicinal como aliada na oncologia veterinária, ampliando perspectivas para novas abordagens terapêuticas.
Palavras- chave:
Cannabis; câncer; linfoma; neutropenia; terapia adjunta
INTRODUCTION
Lymphoma is a malignant neoplasm and represents the most common hematopoietic cancer in dogs. It is classified based on several criteria, including anatomical location, histological grade, histological subtype, and immunophenotype. In terms of anatomical distribution, lymphoma is generally categorized into five main forms: multicentric, mediastinal, gastrointestinal, cutaneous, and extranodal. Among these, the multicentric form is the most prevalent in dogs and is typically characterized by peripheral lymphadenomegaly, which may be regional or generalized (Baskin et al., 2000; Ponce et al., 2010; Zandvliet, 2016). The current standard of care for canine lymphoma is multidrug chemotherapy, which remains the most effective therapeutic approach. In cases of multicentric lymphoma, the overall remission rate reaches approximately 80%, with remission durations typically ranging from four to eight months (Daleck and Nardi, 2016).
Medical cannabis has been explored for its immunomodulatory and antioxidant properties, which may support the management of chemotherapy-induced adverse effects. Evidence suggests that cannabinoids can influence apoptosis in neoplastic cells and mitigate oxidative stress (Guindon and Hohmann, 2011; Pisanti et al., 2017).
The objective of this study was to describe two clinical cases of dogs diagnosed with multicentric lymphoma that underwent chemotherapy in combination with a broad-spectrum, CBD-rich cannabis oil for a duration of 60 days.
ETHICAL ASPECTS
This study was approved by the Animal Use Ethics Committee of the Federal University of Santa Maria (CEUA/UFSM) (No. 6553041122 - ID 003992) and was conducted in accordance with the ethical principles of the National Council for the Control of Animal Experimentation (CONCEA).
CASE REPORTS
The first case involves a 9.4 kg mixed-breed dog presented to the oncology department of a university veterinary hospital with the primary complaint of mandibular lymph node enlargement. On physical examination, generalized lymphadenomegaly was observed, involving the mandibular, superficial cervical, inguinal, and popliteal lymph nodes. Vital parameters were recorded as follows: blood pressure of 130 mmHg, rectal temperature of 38.3°C, capillary refill time of 1 second, and normally pigmented mucous membranes. Cytology of the enlarged lymph nodes revealed findings suggestive of multicentric lymphoma of intermediate to large cell type. For clinical staging, as recommended by the World Health Organization, thoracic radiographs and abdominal ultrasound were performed prior to treatment initiation (Owen et al., 1980; Vail et al., 2010).
At timepoint T0, blood samples were collected for complete blood count (CBC) and oxidative stress analysis before the onset of therapy. Chemotherapy was initiated with a CHOP-based protocol, including vincristine (0.5mg/m²), cyclophosphamide (250mg/m²), and doxorubicin (1mg/kg) over 19 weeks. In parallel, full-spectrum cannabis oil (Amme Medicinal®) at 3% concentration (900mg) was administered orally at a dose of 2.7mg/kg (1 drop/kg, once daily at night) for 60 days. At timepoint T60, blood samples were recollected for CBC and oxidative stress reassessment (Table 1), at which point cannabis oil administration was discontinued. The patient continued chemotherapy alone for an additional six months. Furthermore, periodic blood sampling was performed throughout the 60-day chemotherapy period to monitor myelotoxicity (Table 2).
Before starting treatment, bilateral measurement of superficial lymph nodes was performed using a 6” 150 mm MTX digital caliper in accordance with VCOG consensus guidelines (Vail et al., 2010), as detailed in Table 3.
The second case involves a 3-year-old female Dachshund weighing 10 kg, diagnosed with multicentric lymphoma via cytology and undergoing chemotherapy for the previous three months. At presentation, the patient had no palpable lymph nodes but exhibited significant chemotherapy-induced myelotoxicity, as evidenced by episodes of neutropenia that interfered with treatment continuity. Recorded vital signs included blood pressure of 100mmHg, rectal temperature of 39°C, capillary refill time of 1 second, and normal mucous membranes.
At timepoint T0, blood was collected for CBC and oxidative stress measurement. Simultaneously, full-spectrum cannabis oil (AMME Medicinal®) at 3% concentration (900 mg) was initiated at a dose of 2.7 mg/kg (1 drop/kg, SID at night) for 60 days. The traditional CHOP protocol could not be maintained due to adverse effects from cyclophosphamide, which was replaced with chlorambucil. Thus, vincristine (0.65mg/m²), chlorambucil (1.5mg/m²), and doxorubicin (30mg/m²) were used to manage the multicentric lymphoma. At T60, blood was recollected for CBC and oxidative stress evaluation (Table 1), after which cannabis oil administration was discontinued. The patient continued chemotherapy alone for two more months. During the 60-day treatment period, blood samples were periodically collected to monitor myelotoxicity (Table 2).
DISCUSSION
Lymphoma is one of the most chemotherapy-responsive neoplasms in dogs, offering high remission rates (Moore, 2016). Treatment response in these cases was evaluated according to the VCOG criteria (Vail et al., 2010). In the present report, Patient 1 achieved complete remission following the third chemotherapy session (Table 3) and maintained this status throughout the protocol, with relapse occurring six months after completing the 19-week CHOP regimen without maintenance therapy. Patient 2 was already in complete remission at the time of initial sampling.
During chemotherapy, adverse effects are common due to the nonspecific nature of cytotoxic agents, which target not only tumor cells but also rapidly dividing healthy cells, especially those in the immune and gastrointestinal systems. This often results in side effects such as vomiting, diarrhea, anorexia, and myelotoxicity-most notably neutropenia (Leblanc et al., 2021).
Cannabidiol (CBD), one of the major bioactive compounds found in cannabis, has gained attention as a promising therapeutic agent for dogs undergoing chemotherapy. Studies suggest that CBD may help reduce chemotherapy-associated side effects such as nausea and vomiting, while also improving appetite and overall well-being (Kogan et al., 2019). In this study, the use of CBD was associated with the absence of chemotherapy-induced side effects, suggesting that cannabis administration may have contributed to this favorable outcome.
Regarding oxidative stress findings, different antioxidant responses were observed between the two patients at T0 and T60. Patient 1 was under acute chemotherapy exposure at the time of collection, leading to antioxidant depletion, as evidenced by decreased catalase and GST activity-an adaptive response to mitigate oxidative stress. Despite this, ROS levels remained stable, and TBARS decreased. Patient 2, on the other hand, was experiencing chronic chemotherapy exposure, triggering an adaptive compensatory antioxidant response. This was evident in the increased catalase activity at T60, while TBARS levels rose, indicating persistent oxidative cell damage. These findings suggest that Patient 2s cells were attempting to adjust to prolonged oxidative stress through enhanced antioxidant defenses.
CBD may act directly as an antioxidant, altering both oxidant and antioxidant levels and activity. It can disrupt free radical chain reactions, neutralize reactive species, or convert them into less active forms (Borges et al., 2013). Moreover, the entourage effect, a phenomenon where cannabis compounds work synergistically to enhance therapeutic outcomes, highlights the importance of using full-spectrum oil. This synergy enhances the anti-inflammatory and immunomodulatory actions by targeting different pathways to achieve the same effect (Anil et al., 2022).
Medicinal cannabis is emerging as a promising adjunct in cancer therapy for animals, offering a wide range of benefits beyond its antitumor properties. Its immunomodulatory and antioxidant effects may protect against oxidative damage induced by both the disease and conventional treatments. By alleviating symptoms such as nausea, pain, and anorexia, cannabis may mitigate chemotherapys harmful impact on healthy cells. In summary, the combination of cannabis and chemotherapy represents an innovative and potentially effective strategy for managing canine lymphoma. This integrative approach not only enhances patient quality of life by reducing symptoms but may also offer cellular protection throughout treatment. While current data support the potential of this complementary therapy, further research is essential to validate and optimize its benefits.
CONCLUSION
Based on the reported cases and the analyses performed, it can be concluded that the use of full-spectrum cannabis oil rich in cannabidiol (CBD), in combination with chemotherapy for the treatment of multicentric lymphoma in dogs, may contribute to the reduction of side effects such as myelotoxicity and may also offer a potential protective effect against oxidative stress. These findings highlight the importance of considering patient individuality when administering complementary therapies such as cannabidiol, as well as the need for further studies to determine the most effective dosages and treatment protocols. Moreover, the adaptive response observed in antioxidant enzyme levels, such as catalase, suggests that the patients organisms may attempt to compensate for chemotherapy-induced oxidative stress-an aspect that deserves further investigation regarding the integration of cannabidiol in the management of neoplasms in dogs.
ACKNOWLEDGMENTS
We would like to thank the Associação Brasileira de Pacientes de Cannabis Medicinal (AMME Medicinal®) for their partnership in the development of this work. We also extend our gratitude to the Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Council for Scientific and Technological Development (CNPq) for funding this research.
REFERENCES
- ANIL, S.M.; PEERI, H.; KOLTAI, H. Medical cannabis activity against inflammation: active compounds and modes of action. Front. Pharmacol., v.13, p.908-198, 2022.
- BASKIN, C.R.; COUTO, C.G.; WITTUM, T.E. Factors influencing first remission and survival in 145 dogs with lymphoma: A retrospective study. J. Am. Anim. Hosp. Assoc., v.36, p.404-409, 2000.
- BORGES, R.S.; BATISTA JR., J.; VIANA, R.B. et al. Understanding the molecular aspects of tetrahydrocannabinol and Cannabidiol as antioxidants. Molecules, v.18, p.12663-12674, 2013.
- DALECK, C.R.; NARDI, A.B. Oncologia em cães e gatos. [São Paulo]: Roca, 2016.
- GUINDON, J.; HOHMANN, A.G. The endocannabinoid system and cancer: therapeutic implication. Br. J. Pharmacol., v.163, p.1447-1463, 2011.
- KOGAN, L.; SCHOENFELD, T.R.; HELLYER, P.; RISHNIW, M. US veterinarians’ knowledge, experience, and perception regarding the use of cannabidiol for canine medical conditions. Front. Vet. Sci., v.5, p.338, 2019.
- LEBLANC, A.K.; ATHERTON, M.; BENTLEY, R.T.; BOUDREAU, C.E. et al. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) following investigational therapy in dogs and cats. Vet. Comp. Oncol., v.19, v.311-352, 2021.
- MOORE, A.S. Treatment of T cell lymphoma in dogs. Vet. Rec., v.179, p.277-277, 2016.
- OWEN, L.N.; UNIT, W.H.O.V.P.H.; ONCOLOGY, W.C.C.C. TNM classification of tumours in domestic animals. OWEN, L.N. (Ed.). VPH/CMO/80.20. Geneva: World Health Organization, 1980.
- PISANTI, S.; MALFITANO, A.; CIAGLIA, M.; LAMBERTI, M. Canabidiol: estado da arte e novos desafios para aplicações terapêuticas. Pharmacol. Therap., v.175, p.133-150, 2017.
- PONCE, F.; MARCHAL, T.; MAGNOL, J.P.; TURINELLI, V. et al. A morphological study of 608 cases of canine malignant lymphoma in France with a focus on comparative similarities between canine and human lymphoma morphology. Vet. Pathol., v.27, p.414-433, 2010.
- VAIL, D.M.; MICHELS, G.M.; KHANNA, C.; SELTING, K.A. et al. Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)-A Veterinary Cooperative Oncology Group (VCOG) consensus document. Vet. Comp. Oncol., v.8, p.28-37, 2010.
- ZANDVLIET, M. Linfoma canino: uma revisão. Vet. Q., v.36, v.76-104, 2016.
