Harnessing Our Innate Endocannabinoid System to Conquer Alzheimer’s Disease
By Stephanie Finucane
Our endocannabinoid system (ECS) may not be a well-known body system, but it is becoming increasingly well-known in many research circles as a potential avenue for the prevention and alleviation of Alzheimer’s disease (AD). In the realm of conventional medicine, AD remains a sub optimally treated disease. However, the ECS offers hope.
Alzheimer’s disease is believed to involve “extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein,”1 with a marked decline in endogenous acetylcholine production in the brain as the disease progresses. (Acetylcholine is believed to play an important role in memory and thinking.2) Additionally, the disease course includes “excitatory glutaminergic activity that leads to neuronal damage.”2
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As conventional medicine tends to treat symptoms, the conventional approach to treating mild to moderate AD focuses on cholinesterase inhibitors, which inhibit the degradation of acetylcholine.2 Treatment for moderate to severe AD includes N-methyl D-aspartate (NMDA) receptor antagonists, which help to regulate excitatory glutaminergic activity. Unfortunately, these treatments typically help reduce symptoms only for a limited time, while also causing unpleasant side effects, such as headaches, dizziness, nausea, vomiting, fatigue, diarrhea, and weight loss.2
In contrast to treating symptoms, naturopathic medicine recommends identifying and treating the “root cause of any condition,” writes Kellie Raydon, ND, MSOM, in an article entitled, “Using the Endocannabinoid System to Address Alzheimer’s Disease.”2 Targeting acetylcholine and glutamate activity, while having an effect on neuropsychiatric functioning, does not address the root cause of the cognitive symptoms, writes Raydon.2
Instead, naturopaths like Raydon advocate accessing the root cause of Alzheimer’s disease through the ECS, which is thought to play a role in “neuroprotection and neuroregeneration.”2 A neuromodulatory system, the ECS includes cannabinoids (eg, acid ethanolamide anadamide [AEA] and 2-arachidonoylglycerol [2-AG]) produced by the body, their receptors, and the enzymes that inactivate the endocannabinoids.2,3 Endocannabinoid receptors are located in the central and peripheral nervous systems, and in immune cells. The enzymes that deactivate endocannabinoids are located throughout the body, including the brain, connective tissues, organs, and glands—as well as immune cells. Therefore, the ECS has an expansive reach throughout the body and endocannabinoids are considered “a bridge between body and mind.”2,4 Knowing how the ECS works could reveal “a mechanism that could connect brain activity and states of physical health and disease.”2,4
“The more we investigate the ECS, the more we are seeing how any dysfunction in this system could be a possible underlying root cause of AD,” writes Raydon.2 Indeed, looking at dysfunction in the ECS reveals possible therapeutic routes for the prevention and treatment of AD. For example, apolipoprotein E (ApoE), when present as ApoE4, interferes with ability of the ECS receptor sortilin to properly uptake and convert polyunsaturated fatty acids into endocannabinoids.2 Instead, ApoE3 should be binding to sortilin to allow the orderly process of “neuronal endocannabinoid metabolism and action.”2 By addressing this receptor binding dysfunction in the ECS, endocannabinoid function can be restored,
potentially providing a preventive strategy for AD. (ApoE4 allele is “the main risk factor for late-stage AD.”2)
Additionally, the endocannabinoid 2-AG provides neuroprotection against one of the pathologic mechanisms of AD called amyloidosis.2 Recent research demonstrates that increasing the level of the endocannabinoid 2-AG by “inhibiting its hydrolysis has potential as a novel efficacious therapeutic approach for preventing, ameliorating or treating AD.”2,5 In other words, taking the steps to ensure that levels of the endocannabinoid 2-AG are high may help protect against amyloidosis.
Another way the ECS may be harnessed for the prevention and treatment of AD includes the use of exogenous cannabinoids. Several studies have demonstrated that cannabinoids “reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles,” which are the “key hallmarks of late-onset AD.”2 Additionally, cannabinoids have been shown to reduce symptoms of dementia, such as behavioral disturbances.2
Perhaps even more promising, Raydon points out the “entourage effect” commonly seen with phytocannabinoid use. The commonly seen synergy of compounds within one plant or derived from the combination of plants is another reason for interest in targeting the ECS regarding AD. This synergy of combinations of cannabinoids is evident in studies targeting the ECS with treatments for AD.
1. Cooray R, Gupta V, Sophocles C. Current aspects of the endocannabinoid system and targeted THC and CBD phytocannabinoids as potential therapeutics for Parkinson's and Alzheimer's diseases: a review. Neurobiol. 2020;57(11):4878-4890.
2. Raydon K. Using the endocannabinoid system to address Alzheimer’s disease. Townsend Letter. 2020;447:49-52.
3. Lu H-C, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry. 2016; 79(7):516–525.
4. Alger BE. Getting high on the endocannabinoid system. Cerebrum. 2013:14.
5. Chen X, Zhang J, Chen C. Endocannabinoid 2-arachidonoylglycerol protects neurons against β-amyloid insults. 2011;178:159-168.