Canine Cognitive Dysfunction and Cannabis

Canine Cognitive Dysfunction (CCD) is a progressive neurodegenerative disorder of senior dogs. (1, 2) Dogs with CCD show behavioral alterations such as disorientation, altered interactions with owners, other pets and the environment, sleep-wake cycle disturbance, house-soiling and changes in activity. (2, 3) CCD is dog dementia.

CCD is an umbrella term for four separate cognitive forms identified by Leticia Fanucchi, DVM, PhD, a veterinary behaviorist and director of Veterinary Medicine Behavioral Services at Washington State University’s Veterinary Teaching Hospital. (10)

Involutive Depression:
Depression occurring in the dog’s later years, similar to chronic depression in humans. Several factors may be involved, but untreated anxieties seem to play a key role. Because some of the symptoms of canine dementia — circling, wandering and house soiling—often result in the dog’s confinement, anxiety can increase, which, in turn, worsens the symptoms. Other symptoms of this form of CCD include lethargy, sleep disorders, decreased learning and vocalizing. (10)

Dysthymia: This often involves loss of awareness of body length and size. Other symptoms include disrupted sleep-wake cycles; constant growling, whining or moaning; and aggressive behavior. Causes of this form are thought to include hyperadrenocorticism (such as Cushing’s disease) and long-term steroid therapy. (10)

Hyper-Aggression: In old dogs, hyper-aggression is associated with the dysfunction of structures related to the neurotransmitter serotonin. Cortical tumors may also be involved. “Dogs with this form of CCD lose their ability to communicate with other animals,” explains Fanucchi. “They neither give appeasing signals to other pets in the house nor understand when others send them. They bite first and warn second.” (10)

Confusional Syndrome: This involves a profound decline in cognitive ability. Dr. Fanucchi warns, it is the closest thing to Alzheimer’s in humans. (10)

Learn more about Canine Cognitive Dysfunction and how Cannabis might help.

Coming home to a wagging tail and sloppy kisses is simply the best. The mutual feeling has developed from thousands of years of the canine-human relationship. Mutual feelings? Yes. Investigators at Emory University found that dogs' brains go crazy with the excitement when they see a familiar face. Like humans, as dogs age they can begin to forget those familiar faces, displaying signs of CCD. Dogs naturally accumulate deposits of the protein beta-amyloid (Aβ) in the brain. (4) Human Alzheimer’s disease (AD) is widely believed to be driven by the production and deposition of the Aβ. (6) In fact, researchers have developed the amyloid cascade hypothesis, the deposition of amyloid β protein, the main component of the plaques, is the causative agent of Alzheimer's pathology and that the neurofibrillary tangles, cell loss, vascular damage, and dementia follow as a direct result of this disposition. (11) Canines and humans actually share the same Aβ sequence and both show increased oxidative damage. As a result, dogs can show impaired learning and memory as they age. (4)

Sadly, dogs age faster than we do. In fact, recent research indicates that the 'one human year is equivalent to seven dog years' is inaccurate. A study on Labradors showed they age more in their younger years, while the aging process slows as they get older. For rough comparisons, an 8 week old puppy is equivalent to a 9 month old baby, a 1 year old is a 30 year old adult and a 6 year old dog is approximately 60 years old. (12, 13) Age and chronic systemic inflammation are risk factors for many Central Nervous System diseases, including depression and Alzheimer’s [and Canine Cognitive Dysfunction], and the elevation of peripheral inflammation in old individuals frequently leads to cognitive decline. It follows that there is a complex interrelationship between nerve cell proteotoxicity, inflammation, aging and CNS disease. (7, 8, 9)

Can Cannabis help protect dogs' against Canine Cognitive Dysfunction? The answer is...I like to think so!

A patent the United States Government holds states that Cannabinoids provide neuroprotectant propertients. US Patent US6630507 B1 states "The Cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s disease and HIV dementia. Non-psychoactive Cannabinoids, such as Cannabidiol, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive Cannabinoids at high doses (15)."

Dogs are not human?!? No, but but like humans they have an Endocannabinoid System. The ECS is intimately involved with the brain, cognitive functions and disease. Research indicates that ECS receptors CB1 and CB2 and endocannabinoids are involved during times of injury such as a traumatic brain injury or the accumulation of Amyloid plaque production.

Endocannabinoids can be produced in response to stress, (7, 7-44, 7-45) and in rodent AD, models Cannabinoids reduce Aβ accumulation and improve memory. (7) THC also reduces inducible huntingtin protein overexpression in laboratory cells, (7) and both THC and endocannabinoids reduce inflammation. (7,) Several synthetic, plant derived and endogenous Cannabinoids are able to prevent the accumulation of intraneuronal Aβ, reduce the production of eicosanoids, and block nerve cell death. Therefore, it is reasonable to conclude that there is a therapeutic potential of Cannabinoids for the treatment of Alzheimer's (7) and Canine Cognitive Dysfunction.

Further, investigators at San Diego area Stalk Institute have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in Cannabis can promote the cellular removal of amyloid beta. Granted the research was conducted on laboratory created neurons in an in-vitro study but it can still show insight into the role of inflammation in Alzheimer's disease. “Although other studies have offered evidence that Cannabinoids might be neuroprotective against the symptoms of Alzheimer’s [and Canine Cognitive Dysfunction], we believe our study is the first to demonstrate that Cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells,” says Salk Professor David Schubert, the senior author of the paper. (14)

Cannabidiol (CBD) is also a neuroprotectant. To the benefit of stoners, research shows CBD protects the hippocampus from changes caused by heavy consumption of THC. (from previous article on smoke cbd daily) A side note, daily smokers of Cannabis should also consume CBD daily. Alzheimer's is characterized by the loss of hippocampal neurons and in a research model, the activation of ECS receptor CB2 might protect against Aβ toxicity. (16)

Oxidative stress occurs naturally, playing a role in the aging process. It is an imbalance between the production of free radicals and the body’s ability to counteract their damaging effects through neutralization with antioxidants. (5) Oxidative stress provides the body the ability to rid itself of damaged cells and proteins and replace them with new molecules, but the accumulation of oxidative damage and free radicals can reach an unhealthy level, leading to illness. Our environment can lead to an increase in oxidative stress and unfortunately, our dogs are not immune! Potential causes of increased oxidative stress, both in human and canines, are pollution, poor quality food containing chemicals, UV light, radiation, emotional stress and more. Some diagnosis linked to oxidative stress and damage are cancer, chronic inflammation, autoimmune conditions, heart disease, neurodegenerative diseases such as Alzheimer's [and Canine Cognitive Dysfunction], strokes and more. (15) Research shows that THC, Cannabinol (CBN) and CBD are potent lipophilic antioxidants. (17)

How Can I Give My Dog Cannabis

Obviously dogs don't smoke pot but can utilize Cannabis in several forms. Edible treats have become a popular way to introduce Cannabinoids into a dog's health regimen with companies flooding the market with CBD products. For non-legal Cannabis states, CBD is federally legal and available in all fifty states making it an excellent option. Another popular product on the shelves are tinctures, a liquid oil based application. Many people apply and mix the tincture into food. Another way to use a tincture is by giving it as a pill; I combine multiple tinctures, one has CBD:THC and the other is THCA, into a vegetable gelatin capsule for a mixture of THC, CBD and THCA. For CBD only treats and products SATIVAisticated only recommends CW Botanicals, creators of the original Charlotte Web Strain made famous on the national news and Theramu, holders of the patent for using Emu oil as the transdermal carrier of Cannabinoids.

Dr. Martin Goldstein, DVM and creator of Dr. Marty's Dog Food recently discussed the use of Frankincense to help with Canine Cognitive Dysfunction. Frankincense is an ancient oil that’s chock-full of antioxidants. That’s why it’s been used for thousands of years to help soothe sore muscles, boost immunity, and reduce skin irritation…And best of all, it's easily absorbed right into your pup's skin! (18)

He provides easy instructions:
Step 1: Pour 2-3 drops of Frankincense (you don’t need much, it’s very potent) into your palm and rub both hands together.
Step 2: Call your dog over and let him or her smell your hands so they can get used to it. Once your dog is comfortable…
Step 3: Massage the side of your dog’s face in circular motions with both hands, just under their ears and above their jaw.
Bonus: If your dog is scared of their weekly bath, this is an excellent way to calm them down before they get into the tub.

Excellent tip from Dr. Marty and it got me to thinking, I use Cannarignals (CBD:THC transdermal utilizing Emu Oil) transdermal rub on my temples when experiencing a headache to alleviate pain and throbbing...and it works. Rubbing a transdermal topical on the temple, located in the soft tissue right outside the ear canal can possibly lead to health benefits. At the very least, I can foresee it having a calming effect on your pup.

Improving Our Dog's Endocannabinoid Tone

Like their human parents, dogs have an Endocannabinoid tone. For medical doctors and veterinarians, it is a relatively unexplored aspect to health. Up until a few years ago, it was against the rules of the California American Veterinarian Association for vets to discuss Cannabis with their patients. And now, many veterinarians are not comfortable discussing Cannabis because they do not know much about it or the Endocannabinoid System.

Believe it or not, many things we can do to improve our ECS tone will also work for dogs. Good nutrition is foundational to health and overall wellness. Over-processed foods like a lot of the dry dog kibble available can lead to poor nutrition, illness and increased oxidative stress. Besides low quality food, under feeding, over consumption, parasites and medical issues can also affect the Endocannabinoid System tone.

Nutrition is the foundation to good health and omega 3‘s are the building blocks for Endocannabinoids and help stabilize function of the ECS. They have been shown to help with depression and mood stabilization (3, 4 from supporting endocann system post). Omega 3's from ocean based sources with

In some cases, dogs can take probiotics to improve their intestinal health. Probiotics can help reduce inflammatory processes and modulate the ECS's CB1 receptor expression. (19) With that recommendation, a recent study identified probiotic use in dogs are typically unable to colonize the gut, the metabolites they produce during their transit through the GI tract can ameliorate clinical signs and modify microbiome composition. (20) We periodically give our 14 year old Pomeranian Terrier mix probiotics when he has stomach issues but it is not a daily medication.

The environment, physical and mental, affects the Endocannabinoid System. Physical locations contaminated with pollutants, toxins and other trash is harmful to dogs. Being indoor or outdoor pups can also play a role in the ECS tone. Outdoor dogs are more prevalent to skin cancer, especially on the ears and the nose. Dogs indoors with too much UV light can also experience decrease tone. Research over the past three to four decades has clearly established that psychological stress affects immune system outcomes, including inflammatory processes, wound healing, and responses to infectious agents and other immune challenges such as auto-immune and cancer. (21) An example of psychological stress in dogs is separation anxiety, a condition that can lead to continual barking or destruction of property.

Easy to Over-Supplement and Over-spend

It is easy to over-supplement and overspend when treating our loved ones. It is can also potentially cause harm with kidney damage and gallstones with the use of too many vitamins. The use of Cannabis and pets should be done with the utmost care possible. The use of cannabinoids can cause cardiac irregularities, confusion, dizziness, unsteadiness and euphoria in humans and can do the same in pets. Further, CBD is the more complicated molecule compared to THC, and has the potential to interact with more veterinarian prescribed medications. Veterinarians should be kept aware of Cannabis use by their patients. We also recommend a consultation with a Canna-Nurse when thinking about adding THC to your pet’s Cannabinoid regime or if they already are on prescription medications.

References
1) Maria Cristina Osella, Giovanni Re Rosangela, Odore, Carlo Girardi, Paola Badino, Raffaella Barbero, Luciana Bergamasco; Canine cognitive dysfunction syndrome: Prevalence, clinical signs and treatment with a neuroprotective nutraceutical; Applied Animal Behaviour Science, Volume 105, Issue 4, July 2007, Pages 297-310 — Study
2) Ozawa M, Inoue M, Uchida K, Chambers JK, Takeuch Y, Nakayama H. Physical signs of canine cognitive dysfunction. J Vet Med Sci. 2019;81(12):1829-1834. doi:10.1292/jvms.19-0458 — Study
3) Landsberg GM, Nichol J, Araujo JA. Cognitive dysfunction syndrome: a disease of canine and feline brain aging. Vet Clin North Am Small Anim Pract. 2012;42(4):749-vii. doi:10.1016/j.cvsm.2012.04.003 — Study
4) Cotman CW, Head E, Muggenburg BA, Zicker S, Milgram NW. Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction. Neurobiol Aging. 2002;23(5):809-818. doi:10.1016/s0197-4580(02)00073-8 — Study
5) Chris Kresser; What Really Causes Oxidative Damage?; Kresser Institute, June 14, 2018 — Study
6) Murphy MP, LeVine H 3rd. Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis. 2010;19(1):311-23. doi: 10.3233/JAD-2010-1221. PMID: 20061647; PMCID: PMC2813509. — Study
7) Currais, A., Quehenberger, O., M Armando, A., Daugherty, D., Maher, P., & Schubert, D. (2016). Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids. Npj Aging and Mechanisms of Disease, 2(1). doi:10.1038/npjamd.2016.12 — Study
8) Wright, A. L. et al. Neuroinflammation and neuronal loss precede Abeta plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease. PLoS ONE 8, e59586 (2013) — Study
9) Howcroft, T. K. et al. The role of inflammation in age-related disease. Aging (Albany NY) 5, 84–93 (2013). — Study
10) Susan and Michael Cain, Canine Dementia — Signs, Symptoms, Treatments; The Bark, October 2017, Updated February 2020 — Study
11) Ricciarelli R, Fedele E. The Amyloid Cascade Hypothesis in Alzheimer's Disease: It's Time to Change Our Mind. Curr Neuropharmacol. 2017;15(6):926-935. doi:10.2174/1570159X15666170116143743 — Study
12) Wang et al., Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome
2020, Cell Systems 11, 176–185 August 26, 2020, Elsevier Inc., doi.org/10.1016/j.cels.2020.06.006 — Study
13) Aylin Woodward; Your 1-year-old dog isn't 7 human years old, contrary to the traditional math. It's more like 30 years old, new research shows.; Business Insider, Jul 3, 2020 — Article
14) Salk Institute; Cannabinoids Remove Plaque-Forming Alzheimer's Proteins From Brain Cells; June 27, 2016 - Article
15) Dr. Joseph Rosado, MD, M.B.A, Chief Medical Officer, Antioxidant Benefits of Marijuana; Posted by Marijuana Doctors on 06/28/2019, January 21, 2020 — Article
16) Zhao J, Wang M, Liu W, Ma Z, Wu J, Activation of cannabinoid receptor 2 protects rat hippocampal neurons against A-induced neuronal toxicity, Neuroscience Letters (2020), doi: https://doi.org/10.1016/j.neulet.2020.135207 — Study
17) Marsicano, G., Moosmann, B., Hermann, H., Lutz, B., & Behl, C. (2002). Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. Journal of Neurochemistry, 80(3), 448–456. doi:10.1046/j.0022 — Study
18) Dr. Marty
19) Giulio G Muccioli, Damien Naslain, Fredrik Ba¨ckhed, Christopher S Reigstad, Didier M Lambert, Nathalie M Delzenne and Patrice D Cani: The endocannabinoid system links gut microbiota to adipogenesis; Molecular Systems Biology 6; Article number 392; doi:10.1038/msb.2010.46 — Study
20) Pilla R and Suchodolski JS (2020) The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease. Front. Vet. Sci. 6:498. doi: 10.3389/fvets.2019.00498 — Study
21) Seiler A., Fagundes C.P., Christian L.M. (2020) The Impact of Everyday Stressors on the Immune System and Health. In: Choukèr A. (eds) Stress Challenges and Immunity in Space. Springer, Cham. https://doi.org/10.1007/978-3-030-16996-1_6 — Study