04 Dec Neurological benefits of Phytocannabinoids – Canine Cognitive Dysfunction

Currently, the top reason for vets prescribing CBD oil through PetCann is for chronic pain and/or osteoarthritis.  But what about patients presenting with co-morbidities?  So many of our older patients present not only with pain, but also with some levels of anxiety and often various stages of doggy dementia.  While some of our go-to prescribing options for managing osteoarthritis have negligible effect or worse still, potential negative effects for cognition, CBD oil in fact can be quite beneficial for the patient with CCD. 

Canine Cognitive Dysfunction (CCD), considered the canine analogue of human Alzheimer’s disease, is characterized as a slowly progressive deterioration of behaviour and cognitive ability involving mitochondrial dysfunction, oxidative brain injury, cerebral inflammation and deposition of amyloid plaques.

CCD is more common than perhaps once appreciated. As our pet populations age, the incidence of CCD has become more pronounced. It is not a function of normal aging, just as Alzheimer’s is not normal as humans age, rather both occur at an increased incidence in the aging.  Studies show that 28% of dogs aged 11 to 12 years exhibit CCD, which increases to 68% in dogs aged 15 to 16 years. While there is currently no cure for CCD, early identification and intervention can lead to better management of the condition. 

Recall the DISHAA acronym which can aid in early detection:

D- Disorientation in otherwise familiar situations

I – Interactions which change with family members

S – Sleep-wake cycles disrupted – pacing / vocalizing / restless during sleep time

H – House soiling, learning, memory – normal learnt behaviour lost

A – Activity – levels reduce

A – Anxiety – levels change

If dysfunction is observed in two or more categories above, and other medical conditions have been ruled out, a diagnosis of exclusion of CCD can be concluded.  This does not of course exclude other behavioural or medical issues, which often coexist. Chronic inflammation from various diseases can significantly increase the risk of cognitive decline, contributing to brain aging.

Mitochondrial dysfunction plays a crucial role in the pathogenesis of CCD.

Healthy mitochondria produce energy efficiently while generating minimal waste. However, as dogs age, mitochondrial efficiency in many cells decreases, leading to reduced energy production and increased waste.  Waste, in the form of free radicals, contributes to oxidative stress and damage of surrounding cells. Neuronal membranes, rich in polyunsaturated fatty acids, are particularly vulnerable to oxidative damage and are damaged through the increased waste production of aging, less efficient mitochondria.  

Oxidative stress arises when there is an imbalance between reactive oxygen species (ROS) production and the body’s ability to detoxify these harmful products. This imbalance as noted already has a direct toxic effect on neurons but can also compromise the blood-brain barrier, impairing cerebral perfusion, and further exacerbate cognitive decline.

Autophagy is impaired when there is dysfunctional mitochondria, reducing the normal ability to catabolise proteins. This leads to protein aggregation and in turn formation of plaques and tau protein accumulation and impacts neurotransmission.  Impairment of both inhibitory and excitiatiory interneurons can lead to neurotoxicity and cell death.

Mitochondrial dysfunction hinders glucose uptake and disrupts energy generation by the mitochondria which relies on aerobic oxidation of glucose, contributing to the ongoing cycle of dysfunction .  Mitochondria is also responsible for maintaining intracellular calcium levels and with dysfunction leads to a series of signals that ultimately can result in membrane swelling and apoptosis.

How cannabis medicine may help

The endocannabinoid system, with its G-protein coupled receptors and their endogenous lipid ligands, is an important molecular system responsible for controlling homeostasis and may be responsible for the therapeutic modulation of oxidative stress in various diseases, including CCD. Cannabidiol, CBD, is one of the most pharmacologically active Phyto cannabinoids; being non-psychoactive and having many beneficial pharmacological effects, particularly anti-inflammatory and antioxidant effects.

CBD, is a powerful antioxidant, scavenging free radicals, interrupting free radical chain reactions and reducing ROS production whilst also decreasing amyloid formation in neurons.  CB2 activation decreases ROS and TNF alpha levels further contributing to reduced oxidative stress and inflammation. CBD has been shown to have neuroprotective benefits – including reducing inflammatory cytokine production, reducing vascular changes and neuroinflammation and helps reduce production of Aβ plaques and reduce tau protein aggregation. 

In human patients, cannabis oil has been shown to help reduce distress, agitation and aggression in Alzheimer sufferers and improve their appetite, mood and sleep quality.  Understanding CBD affects both GABA and serotonin receptors, anxiolytic properties of CBD also provide improved wellbeing and quality of life for CCD patients.  To date, CBD has most discussed and shows much promise in treatment, however minor cannabinoids, CBG and CBDA may further provide additional benefit in neuroprotection.

CBD is generally delivered in an MCT (Medium chain triglyceride) oil.  MCT oil in itself improves memory and learning ability and is often recommended for CCD patients.  Recalling the impaired ability for damaged neurons to utilize glucose, MCT oil provides an alternative energy source, in turn improving mitochondria function and energy metabolism.  It also helps to reduce the levels of brain amyloid precursor proteins.

Whilst we continue to learn more about the potential benefits of cannabis medicine for the CCD patient, CBD is well worth considering alongside dietary modification, nutraceuticals, physical therapy and cognitive enrichment including regular exercise, social interactions and mental stimulation.  As chronic inflammation from various diseases significantly increases the risk of cognitive decline, CBD could also be considered as part of preventative steps for the middle aged and aging patient to reduce progressive cognitive decline and many other conditions that present in the aging patient.

REFERENCES:

1. Atalay, S., Jarocka-Karpowicz, I. and Skrzydlewska, E. (2020) ‘Antioxidative and anti-inflammatory properties of cannabidiol’, Antioxidants, 9(1), pp. 21. doi: 10.3390/antiox9010021. Available at: Antioxidative and Anti-Inflammatory Properties of Cannabidiol – PMC (nih.gov)
2. Huntingford, JL Integrative Treatment of Canine Cognitive Dsyfunction AHVMA Journal Volume 63 Summer 2021:10 -22. Available at: Integrative-Treatment-of-Canine-Cognitive-Dysfunction-Volume-63_LR-2.pdf (ahvma.org)
3. Jurcau, A. (2021) ‘The role of natural antioxidants in the prevention of dementia—where do we stand and future perspectives’, Nutrients, 13(2), pp. 282. doi: 10.3390/nu13020282. Available at: The Role of Natural Antioxidants in the Prevention of Dementia—Where Do We Stand and Future Perspectives – PMC (nih.gov)
4. Dewey, C.W., Davies, E.S., Xie, H. and Wakshlag, J.J. (2019) ‘Canine cognitive dysfunction: Pathophysiology, diagnosis, and treatment’, Veterinary Clinics of North America: Small Animal Practice, 49(3), pp. 477-499. Available at: Canine Cognitive Dysfunction: Pathophysiology, Diagnosis, and Treatment – PubMed (nih.gov)
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