The lymphatic system is critical component of the circulatory and immune systems in the body composed of a complex network of lymph, vessels, nodes, and organs (spleen, tonsils) that plays a vital role in maintaining fluid balance, immune response, transport of nutrients and filtration of waste and blood. 

The Lymph is a clear, colorless fluid that circulates through the lymphatic vessels containing immune cells, including lymphocytes, which play a crucial role in the body's immune response. Bone marrow is not an exclusive part of the lymphatic system but is involved in lymphocytes production.

Disruption or dysfunction of the lymphatic system can lead to conditions such as lymphedema (fluid retention and swelling), compromised immune function, and impaired fluid balance.

Canine lymphoma is a type of cancer that affects the dog’s lymphatic system characterized by the abnormal overgrowth and unregulated cellular division of lymphocytes, a type of white blood cell, leading to the formation of tumors in the lymphoid tissues. It accounts for 7–24% of all canine tumors and 83% of all canine hematopoietic malignancies (Vail, Thamm, and Liptak, 2013).

Lymphoma accounts for 15-20% of new cancer diagnoses in dogs commonly seen in middle-aged and older dogs. The genetic component of the disease is still under study but several breeds are predisposed such as: 

• Golden Retriever
• Chow Chow
• Basset Hound
• Rottweiler
• Saint Bernard
• Poodle
• German Shepherd
• Scottish, Airedale, West Highland White, Yorkshire, and Bull Terriers
• English Bulldog
• Beagle

The signs of canine lymphoma can vary depending on the type and location of the tumors. Common symptoms may include swollen lymph nodes, lethargy, weight loss, loss of appetite, vomiting, diarrhea, and increased thirst and urination.

80%-85%Multicentric lymphoma is the most common type of lymphoma in dogs accounting to 80%-85% of lymphomas in dogs. The lymph nodes are enlarged rapidly up to 3-10 times their normal size.

Any lymph node throughout the body could be affected. Though the firm and rubbery lump under the skin is not painful, the dog may experience fever in advanced cases and show signs of weakness, lethargy, anorexia, dehydration.

Lowe, 2004Gastrointestinal or alimentary Lymphoma is the second most common form of lymphoma in dogs accounting to approximately 5% of cases (Lowe, 2004). Majority of the symptoms are found in the intestines.

The dog may experience abdominal pain, vomiting, diarrhea, anorexia, and weight loss.

Cutaneous lymphoma is the most common type of extranodal lymphoma characterized by individual, raised nodules or generally dispersed scaly lesions in the skin, patches of hair loss, discoloration and ulcerations. It may also occur in the lips, gums and the roof of the mouth.

Mediastinal Lymphoma affects the lymphoid organs in the chest such as the mediastinal lymph nodes and thymus. As such, aggressive high-grade malignant T lymphocytes are produced.

Signs include coughing and difficulty in breathing when fluids build up in the chest causing additional pressure on the lungs. Frequent drinking and urination, technically known as polyuria and polydipsia (PU/PD) can also be observed when there is an increase of calcium in the blood.

Extranodal lymphoma is a rare type of lymphoma that targets a specific organ outside of the lymphatic system such as the skin, eyes, kidney, lung, or nervous system.

The clinical signs in dogs would depend on the type of lymphoma. Nonetheless, general signs would include but not limited to:

• Decreased appetite
• Weight loss
• Increased thirst and urination
• Swollen face or limbs
  
  

Diagnosis typically involves a combination of physical examination, blood tests, Fine Needle Aspiration Cytology (FNAC)  imaging studies (such as X-rays or ultrasound), and analysis of lymph nodes or tissue samples through a biopsy which will be reviewed by a veterinary pathologist.

Once diagnosed, further testing such as immunophenotyping may also be done to determine the specific type of lymphoma. Referral to veterinary oncologist will be done for staging.

Just like in humans, canine lymphoma has several stages:

• Stage I - cancer is contained in a single lymph node
• Stage II - cancer is contained in multiple lymph nodes on one side of the diaphragm (either the top or the bottom of the dog).
• Stage III - cancer is only contained in the lymph nodes themselves
• Stage IV - cancer is located in the liver and spleen or hepatosplenomegaly, whether it started there or spread there.
• Stage V - cancer is in the bone marrow, central nervous system, or other parts of the body.
  
  

Treatment options for canine lymphoma may include chemotherapy, radiation therapy, and, in some cases, surgery. The specific treatment plan depends on the type and stage of lymphoma, as well as the overall health and age of the dog.

Chemotherapy is commonly used and can be effective in inducing remission. These drugs could be Vincristine, Lomustine, Cyclophosphamide, Chlorambucil, Prednisone, or L-Asparaginase.

Alongside medical treatments, supportive care is important. This may include managing symptoms, providing a balanced and nutritious diet, and addressing any side effects of treatment.

• Gastrointestinal Upset (Nausea and vomiting)
• Decreased Appetite
• Lethargy and Fatigue
• Bone Marrow Suppression
• Hair Loss (Alopecia):
• Mucositis
• Allergic Reactions
• Changes in Blood Chemistry
• Infection Risk

Cannabidiol (CBD) is a naturally occurring compound in the cannabis plant without psychoactive properties. The oil is extracted from the CBD plant through carbon dioxide extraction, ethanol extraction, isopropyl extraction or lipid infusion.

Entourage effect is the idea that substances that are taken together would give better results than when taken individually due to their synergistic interaction. In the world of CBD, this refers to the teamwork of the 80+ cannabinoids, 100+ terpenes, and flavonoids found in the hemp plant working together to produce the desired “healing effect”.

The endocannabinoid system (ECS) is a ubiquitous major lipid system in the body consisting of endogenous ligands (endocannabinoids), their receptors and enzymes, providing homeostatic balance of the nervous and immune system, and different organ systems.

CBD Oil could alleviate canine lymphoma symptoms and chemotherapy side effects.

1. Anti-Tumor Medication - CBD inhibits tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells (McAllister, Soroceanu & Desprez, 2015) Moreover, the study of Massi, et al in 2004 concluded that CBD was able to produce a significant antitumor activity both in vitro and in vivo, suggesting a possible application of CBD as an antineoplastic agent.
   
   
2. Reduce Inflammation and Pain - Gamble, et al (2018) reported that 2 mg/kg twice daily of CBD oil significantly decreases pain and increases activity in dogs.
   
   
3. Enhance Sleep - CBD blocks anxiety-induced REM (Rapid Eye Movement) sleep alteration via its anxiolytic effect (Hsiao, et al, 2011). According to Platto, et al (2022) anxiety-related behaviors in dogs before and during the Covid-19 lockdown in China were associated with changes in their sleeping habits, which might suggest a deterioration of their welfare.
   
   
4. Help with Nausea - CBD has both anti-nausea/anti-emetic effects (Parker, Rock, and Limebeer, 2011)
   
   
5. Boost Immune System - CBD has anti-inflammatory and immuno-modulating properties in dogs' immune cells by reduction in IL-6 and TNF-α production (Gugliandolo, et al,  2021).
   
   
6. Improve Appetite - there is still no concrete conclusion yet as to how CBD increases appetite in dogs. However, some human scientific studies show that CBD increased appetite as a side effect  to epileptic patients given with CBD (Corroon and Phillips, 2018; Iffland and Grotenhermen, 2018; Hussain et al, 2015)

The extraction process of CBD is a crucial step in obtaining CBD oil, and there are several methods commonly used for this purpose. Here are common methods of CBD Oil extraction:

This method uses carbon dioxide (CO2) under high pressure and low temperature to isolate, preserve, and maintain the purity of the CBD oil. It is considered one of the cleanest methods as it doesn't leave behind any residue.

This method involves the use of solvents like ethanol, butane, or propane to extract CBD from the hemp plant. The plant material is soaked in the solvent, which dissolves the cannabinoids. The solvent is then evaporated, leaving behind concentrated CBD oil.

In this method, olive oil is used to extract cannabinoids from the hemp plant. The plant material is heated to activate the cannabinoids, and then it is mixed with olive oil. This method is safe and simple but may result in a less concentrated product.

This method is less common for CBD extraction but is sometimes used. It involves passing steam through the hemp plant material, causing the CBD oil to evaporate. The steam and CBD oil are then condensed into a liquid.

• Full-Spectrum

Full Spectrum CBD oil also contains other cannabinoids and other plant substances because they are the least processed extract type. Paw Origins Cbd Full-Spectrum (1,000mg) Happy-Furever™ Oil takes advantage of the benefits of the “entourage effect”.

• Broad-Spectrum

Broad-spectrum CBD oil has undergone further process to remove the THC content but the other cannabinoids are still retained. 

• Isolate

CBD Oil isolate is the purest form of CBD oil. It underwent further processes to remove all the other cannabinoids.

CBD comes in different forms with different benefits.

CBD oil tinctures are CBD oil mixed with carrier oil and added with flavors to make it easier, and usually also tastier, to take. The container often comes with a dropper to administer the CBD oil directly in the dog’s mouth or to add to dog food.

CBD capsules are CBD oil placed in a capsule to mask the oil taste, so it may be easier to get your dog to take these.

CBD treats come in both crunchy and chewy forms with CBD oil, to suit your dog's taste buds. These are consumed as they do their other treats.

CBD topical products are also available for dogs for skin-related symptoms or localized symptoms under the skin. These are applied like any other lotion or other topical product.

The role of CBD Oil in managing Lymphoma in dogs is promising. As discussed above, there were already preliminary studies on the role of CBD however, for now, we can say that CBD alleviates the symptoms of Lymphoma and side-effects of chemotherapy.

It is important to note that lymphoma can’t be totally cured with a high incidence of recurrence. In some severe cases, euthanasia had been an option. Nonetheless, managing lymphoma should focus on the quality of life of dogs.