CBD and Its Potential to Treat or Address Alzheimer’s and Dementia

Posted July 1, 2020

Wooden puzzle on the floor in the shape of a brain, with one piece removed waiting to be added.

Dementias are progressive brain diseases that lead to a gradual decrease in the patient’s ability to think, remember, and function normally in day-to-day life. Loss of cognitive ability is as crippling as it is dangerous.

Unfortunately, there is no known cure for these conditions. Current treatment options are severely limited in terms of variety and effectiveness. This has led to the investigation of new therapies, including the effect of cannabinoids, phytocompounds naturally found in the cannabis plant.

Cannabis is widely known for tetrahydrocannabinol (THC) as it is the phytocannabinoid causing the typical euphoric, psychoactive effects. However, there are over one hundred phytocannabinoids in the plant. Another one, cannabidiol (CBD), lacks psychoactive consequences and seems promising for the treatment of various dementias, including Alzheimer's disease and Vascular Dementia.

In this article we will dig deep into the emerging science on whether or not CBD has the potential to address symptoms of dementia and cognitive decline.

The Effects of CBD Inside the Brain

The effect of CBD on the body is mediated by two receptors: CB1 and CB2. (1) Theses are the main receptors through which the endogenous cannabinoid system (ECS) functions. This system has been discovered relatively recently and its main role is to regulate the transmission of nerve impulses throughout the body. (2) Studies reveal that the vital process of this nervous system regulation is typically affected and disordered in dementias.

The ECS is expressed throughout multiple organs in the body, this includes the central nervous system (CNS). CB1 receptors are found mainly in the brain while CB2 receptors are found primarily in peripheral tissues, mostly on various immune cells. CB2 receptors have a role in modulating immune responses, such as the migration of immune cells and the release of immune molecules such as cytokines, some of which regulate the inflammatory process.

However, CB2 receptors are also found in the CNS, mainly on the microglia and in some neurons. During inflammation in the brain, migrating immune cells also contribute to the

presence of CB2 receptors there. The upregulation of CB2 receptors, an increase in their number, seems to coincide with microglial activation. In essence, the brain becomes inflamed and thinking is consequently impaired. Microglia are the resident macrophages in the CNS, they are the mediators of any immune response that occurs in the brain and they are thought to play a major role in the etiopathology of the most common dementia - Alzheimer’s Disease.

A study conducted in mice found that CB1 receptors are significantly reduced in cases of Alzheimer’s. Simultaneously, the beta-amyloid plaques also have CB1 and CB2 receptors. (3) These amyloids are the most typical formations in the brains of patients with Alzheimer’s and they lead to nerve cell death which is related to the overall symptoms. Cannabinoid interaction with these receptors may reduce inflammation and potentially modulate amyloid plaques.

The administration of CBD acts as CB2 selective agonist and blocks the activation of the microglial cells which inhibit microglia-mediated inflammation and neurotoxicity. The study concluded that these endocannabinoid receptors could have a major role in the pathology of Alzheimer’s and CBD might slow down the neurodegenerative processes.

Numerous studies have reported that mice lacking the CB2 receptor have increased inflammation. (4) According to a study published by Amity Institute of Pharmacy, CBD can also help the second most common form of dementia – Vascular Dementia, by improving the blood flow in the brain. (5)

Another review reports that CB2 receptors are significantly increased in the brains of patients with Alzheimer’s and receptor agonists, such as CBD, can attenuate inflammation and improve cognitive impairment in animal models of Alzheimer’s. (6)

Beyond the Anti-Inflammatory Effects of CBD

Apart from reducing inflammation, CBD may also help patients with dementia by reducing oxidative stress, it acts as an antioxidant). This reduces functional decline of brain cells. The antioxidant effect seems to stimulate the brain as reported mostly by in vitro studies. (7, 8, 9) Additionally, there are other trials with mice that report a reduction in oxidative stress with CBD but the exact mechanism remains unknown. (10)

CBD might also counteract the well-known glucose metabolism deficit in brains with Alzheimer’s. This is achieved by activation of CB2 receptors and mediating the glucose uptake in the brain where it is utilized as an important fuel for brain cells. (11)

Evidence that cannabis reduces brain function decline is also coming from animal studies. A study found out that a low dose of cannabis reverses various aging processes in the brain and restores cognitive function in old mice, although that effect is mainly mediated by CB1 receptors and THC. (12)

A 2014 literature review concluded that CBD targets in parallel several processes with key roles in Alzheimer’s. CBD seems to reduce neuroinflammation, excitotoxicity, mitochondrial dysfunction, oxidative stress, and behavioral disturbances. Such a literature review indicates that CBD may be a promising low-cost therapy against Alzheimer’s. (13)

CBD May Act Best in Combination with THC

A study by scientists from Salk Institute found preliminary data that a combination of the compounds in cannabis, including CBD and THC, promotes the removal of the proteins responsible for forming beta-amyloid plaques. (14) This was an in vitro study of nerve cells altered to produce high levels of beta-amyloid similar to the pathological processes in Alzheimer’s. The study revealed that via removal of these plaques and blocking the inflammatory response, cannabinoids can prevent nerve cell death. Other studies have also found that CBD has a neuroprotective effect on the brain that counters the impact of beta-amyloid accumulation. (15)

Clinical trials investigating the effect of cannabinoids on other neurodegenerative disorders have found that CBD is safe and very well tolerated by patients. (16)

A systematic review of twelve clinical trials has also found a very favorable safety profile of CBD. (17) The most common adverse effect reported by studies was mild sedation. According to this review, observational studies seem promising for the effectiveness of CBD, but it is yet to be proven by large clinical trials.

Another literature review from 2017 also concluded that there is preliminary in vitro and in vivo data which proves that CBD, and its seemingly synergistic combination with THC, has potential for Alzheimer’s therapy, but clinical trials in humans are needed in order to prove these possibilities clinically. (18) The review also suggests that the combination of CBD and THC can mediate greater therapeutic benefits than either phytocannabinoid alone, reinforcing the potentially synergistic aspect of these two important phytocannabinoids working together.

Furthermore, another literature review of studies suggests that THC competitively inhibits the enzyme acetylcholinesterase (AChE) ‐ a similar action to prescription anti‐dementia drugs like donepezil. (19)

The psychoactive effects and the risk for possible adverse psychological effects of THC are widely known which is a common concern. However, a growing body of evidence suggests that CBD, when appropriately dosed, can counteract these effects and the combination of both can be safe and effective. (20)

The Current Consensus of Official Organizations

According to the UK Alzheimer’s Society, currently, there is no evidence from human trials to support that cannabis or CBD can treat or prevent dementia including Alzheimer’s. (21) However, they acknowledge that CBD might be effective in managing behavior symptoms and that there are some promising laboratory studies. Large literature reviews have also concluded that population-based studies suggest that cannabinoids reduce dementia-related symptoms such as behavioral disturbances. (19, 22) However, there simply is a lack of high-quality evidence from studies in people.

Currently, CBD is being further investigated and seems effective as a potential treatment of behavioral symptoms related to dementia such as agitation and aggression. (23) Other treatments for this syndrome are quite limited and have serious side effects.

The FDA warns CBD might be associated with liver injury and any claims for benefits are not approved by the agency. So far, the FDA has approved lone CBD-derived product. It is delivered using a significant dose but only indicated for the treatment of epilepsy at this time. (24)

The Take-Home Message

Because the endocannabinoid system is so far-reaching with the human body and the nervous system, using cannabinoids seems to have exciting potential in addressing various conditions, including dementia and especially Alzheimer’s disease. Despite decades of research and an alarming increase in the incidence of dementia/Alzheimer’s, the scarcity of effective treatments for these diseases has pushed medical researchers to investigate the potential utility of CBD.

The majority of the studies in this direction are quite recent, and so far, we have only laboratory experiments in vitro and in animals. Despite the low level of the evidence, the results so far seem promising and a lot of higher-level research will surely follow.

One of the most promising aspects of CBD usage seems to be the treatment of the behavioral syndrome associated with Alzheimer's.

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