Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer’s Disease
This is a randomized, double-blinded, placebo-controlled, crossover trial that aims to 1) determine the efficacy of THC-free cannabidiol (CBD oil) in reducing the severity of agitation among participants and 2) determine whether THC-free CBD oil can reduce the burden on caregivers and increase the participants’ quality of life.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease Dementia Major Neurocognitive Disorder With Aggressive Behavior||Drug: THC-free CBD Oil Drug: Placebo||Phase 2|
Individuals with Alzheimer’s and other forms of dementia often go through a period of significant behavioral and psychological symptoms of dementia (BPSD). It is estimated that up to 90% of persons with dementia (PWD) experience behavior problems at some point. BPSDs can be challenging for both unpaid family caregivers as well as paid caregivers. Family caregivers provide the bulk of care for PWD and number over 15 million. One of the most common types of BPSDs is agitation with a prevalence of up to 87%, based on a recent systematic review. Agitation can lead to impaired daily functioning, prolongation of hospitalization, reduced time to institutionalization, and is associated with higher mortality. Additionally, agitated behavior is associated with increased injury to both patients and caregivers. Based on the 2018 Alzheimer’s disease drug development pipeline report almost 70% of clinical trials related to BPSD are dedicated to agitation behavior. Finding ways to address agitation is necessary to improve overall quality of life for PWD and their caregivers. Currently, there are no medications available specifically for the treatment of BPSDs. The use of benzodiazepines, antipsychotics and mood stabilizing agents are common, but the risks and side effects often outweigh any benefits.
Several small studies have investigated the use of cannabinoids in the treatment of pathology and symptomology of Alzheimer’s disease (AD), as well as treatment of the agitation component of BPSD. A handful of these studies showed that the symptoms of BPSD were decreased with the use of cannabinoids. However, due to small sample sizes, study design, and short trial duration of these studies, the efficacy of these agents on BPSD cannot be confirmed. In addition, cannabinoids have demonstrated anti-oxidant and anti-inflammatory effects, and both processes have been indicated as major contributors to the neurologic effects of AD. Some evidence exists that agitation is related to this neuroinflammatory process. This study will examine the effects of cannabinoids on the behavioral and psychological symptoms of individuals with a dementia diagnosis.
CBD Oil for Dementia and Alzheimer’s Disease: Benefits, Dosage, & Uses
Alzheimer’s disease is the most common age-related neurodegenerative disorder in the developed world.
CBD oil has recently shown a lot of promise as a new treatment for this condition.
How does it work, how can I use it, and what products are the best for treating this debilitating neurological condition?
Alzheimer’s disease (dementia) is the most common age-related neurodegenerative disorder .
It’s becoming more common year by year, causing a lower quality of life to the individuals who suffer from the condition and their families.
Unfortunately, there’s no cure for Alzheimer’s disease yet. However, in recent years, there’s been a lot of hype around CBD oil as a promising treatment for the condition.
Does it live up to the expectations? How does CBD oil help slow the progression of Alzheimer’s disease? What does the research say?
Learn how it works and where to find the best CBD oils for dementia.
MEDICALLY REVIEWED BY
Updated on November 14, 2021
Table of Contents
- The Benefits of CBD Oil For Dementia & Alzheimer’s Disease
- 3. CBD Helps the Body Resist Oxidative Damage
- The symptoms of Alzheimer’s Disease (dementia) come on gradually in 4 stages:
$49 – $229
Royal CBD Oil 30 mL
5 / 5
|Total CBD:||500 – 2500 mg|
|Potency:||16.6 – 83.3 mg/mL|
|Cost per mg CBD:||$0.12 – $0.18|
The Benefits of CBD Oil For Dementia & Alzheimer’s Disease
CBD oil offers several key benefits to Alzheimer’s disease and dementia. However, it takes a while for CBD to work for this condition. For best results, CBD oil should be used for several weeks or months before you can expect any improvement.
The benefits of CBD oil for dementia and Alzheimer’s disease include:
- May protect from beta-amyloid plaques (one of the underlying causes of Alzheimer’s disease)
- May boost blood flow to the brain
- Protects the brain from inflammation and oxidative damage
- May prevent the buildup of TAU protein tangles (another common cause of the condition)
1. CBD May Protect the Brain from Amyloid-Beta
One study showed that cells pre-treated with CBD were better able to survive and resist the damaging effects of amyloid-beta.
Other studies have found that CBD and some of the terpenes found in the cannabis plant have the ability to inhibit an enzyme known as acetylcholinesterase.
This enzyme is responsible for breaking down a neurotransmitter known as acetylcholine, which plays a key role in the process of memory formation and retrieval. It’s especially active in a region of the brain known as the hippocampus, which is one of the first areas to show signs of damage during Alzheimer’s disease.
It’s believed that acetylcholine dysfunction plays a role in the formation of amyloid-beta plaques .
One of the main methods of treatment for Alzheimer’s disease is to improve acetylcholine function. This is generally done by inhibiting the breakdown of acetylcholine by an enzyme called acetylcholinesterase. This may slow the buildup of the damaging amyloid-beta and also improves memory function by increasing acetylcholine levels overall.
Many of the terpenes in full-spectrum CBD oils have been shown to inhibit acetylcholinesterase in-vitro, including:
- Δ-3-carene 
- 1,8-cineole 
- Limonene 
- Thymol 
- γ-terpinene 
Both CBD and THC also inhibit acetylcholinesterase, helping to increase overall acetylcholine levels and reduce the production of damaging amyloid-beta .
Mouse studies have also shown CBD to reduce the neuroinflammatory response to amyloid-beta, as well as the reactive gliosis (neural cell swelling damage) that ensues .
Various cannabinoids have also demonstrated to have a specific activity in the hippocampus, suggesting a deeper support mechanism may also be at play .
2. CBD Oil May Boost Blood Flow to the Brain
One of the main benefits of CBD oil is through its indicated ability to increase blood flow to the brain.
It likely owes these effects to many of the terpenes contained in the plants, including:
- Eucalyptol 
- Caryophyllene oxide 
- Borneol 
CBD itself also improves blood flow indirectly by improving the function of our main endocannabinoid, anandamide .
This naturally occurring cannabinoid is involved with regulating our arteries and veins, helping to control the blood flow throughout the body.
3. CBD Helps the Body Resist Oxidative Damage
There are many different causes of oxidative damage, including:
- Heavy metal exposure
- Poor blood flow to the brain
- Poor glial cell function
CBD oil contains a number of different antioxidant compounds that help stop this damage from occurring in the first place.
Antioxidants work by essentially sacrificing themselves to take the damage from free radicals, so the cells don’t have to. They satisfy the free radicals’ need to steal electrons to balance their charge.
When looking for a CBD oil with these properties, it’s important to choose a product that contains the full spectrum of terpenes, cannabinoids, and flavonoids of the hemp or marijuana plant.
Some of the main antioxidant compounds in cannabis plants include:
- Terpenes (eucalyptol, γ-terpinene, α-Terpineol, pinene) [6, 8, 9]
- Cannabidiol (CBD) [4, 7]
- Tetrahydrocannabinol (THC) 
Using CBD Oil for Alzheimer’s Disease
Getting started with using CBD oil for Alzheimer’s disease is simple.
You need to find a product that contains a full spectrum of terpenes, cannabinoids, and other phytochemicals from your local dispensary or online shop.
The usual dose of CBD for assisting in this condition can vary significantly; however, most people will start anecdotally somewhere around the 300 mg per day mark.
Depending on how this affects each person individually, the dose can either be increased or decreased.
Top Three Best CBD Oils For Alzheimer’s Disease
Will I Notice Benefits Right Away?
The main benefits of CBD oil for Alzheimer’s disease is the theoretical possibility of slowing the progression of the disease.
For this reason, the benefits won’t be as clear as they will be for other conditions such as pain or inflammation.
When it comes to Alzheimer’s disease, CBD oil should be taken every day, along with a balanced diet and regular exercise to get the best effects out of it. Take any medications as prescribed, and be sure to follow up regularly with your doctor, especially before you begin a CBD regimen to avoid interactions and/or if you have liver health issues.
The idea is that the CBD oil might make Alzheimer’s progression slower, helping to increase patients’ quality of life in the long-term. Of course, further clinical research will be needed to demonstrate any true or characteristic benefit.
What is Alzheimer’s Disease?
Alzheimer’s dementia is a chronic degenerative condition affecting the brain.
It results from a gradual breakdown of the grey matter in the brain, resulting in a number of psychological, behavioral, and cognitive changes.
Grey matter makes up the outer portion of the brain and is responsible for most of what we experience as thought. It’s where we make decisions, form memories, and solve problems.
The symptoms of Alzheimer’s Disease (dementia) come on gradually in 4 stages:
Stage 1 [1-4 years]
- Mild lapses in memory
- Increased irritability
Stage 2 [4-8 years]
- Less interest in work or hobbies
- Lower energy levels
- Loss of recent memories
- Language problems
- Mild coordination problems
- Mood swings
- Difficulty navigating
Stage 3 [8-12 years]
- Rambling speech
- Frequent memory issues with larger lapses in time
- Speech difficulties
- Inability to navigate effectively
- Severe irritability and frustration
- Mild-moderate coordination problems
Stage 4 [12+ years (end of life)]
- Inability to walk or conduct normal life activities like bathing or using the bathroom
- Inability to communicate effectively
- Constant forgetfulness
- Inability to recognize close family or friends
- Anger/mood swings
- Fictional understanding of the world around them
The Possible Causes of Alzheimer’s Disease
Despite how common Alzheimer’s disease is, we still lack a thorough understanding of what exactly causes the condition. But, of course, there are a few prevailing theories that are gaining more evidence.
1. Amyloid-beta Plaques
Amyloid-beta is a sticky substance produced in the brain as a byproduct of normal neuron activity.
Normally, the glial cells – a group of special cells in the brain that act as the garbage disposal crew, among other things – come out at night to clear out these plaques, preventing them from building up and causing damage to the neurons.
Unfortunately, as we age, our cleanup crew doesn’t work as efficiently as it used to, allowing this amyloid-beta to build up and form thick plaques on the nerve cells and blood vessels. It is also likely that the fluids in the brain do not flush out as well as they used to also because of this plaque build-up.
Eventually, this causes the nerve cell to die off and blood flow to worsen.
As more of these cells continue to die, we start to see an increase in neuroinflammation, tau protein tangles, and the symptoms of Alzheimer’s disease progress.
Interestingly, a strong genetic link was found between the ApoE4 enzyme — an enzyme responsible for helping glial cells clear out amyloid-beta — and the risk of developing Alzheimer’s disease . More recently discovered, ApoE4 is also linked to increased tau protein tangles, which are more strongly correlated to worse clinical symptoms than amyloid-beta plaques . However, amyloid-beta plaques still probably play an important role in starting the disease process.
This makes preventing amyloid-beta a primary treatment aim for doctors trying to treat or prevent the condition.
2. Tau Protein Tangles
The most probable cause of Alzheimer’s disease is a buildup of another substance in the brain, known as tau proteins .
These tau proteins accumulate and become neurofibrillary tangles, which are toxic for neurons. However, this mechanism is poorly understood and is actually associated with a lot of other conditions. Any condition involving issues with these proteins are referred to as tauopathies.
Proteins are the main building blocks of life – much of what we’re made of can be distilled down to a protein. These tau proteins are just one type of protein that makes up our body. When they start to break down, they form unorganized “tangles”.
They’re essentially “knots in the nerve cells”, building up inside and hurting their ability to function normally.
There are a few experimental medications currently being tested that target these tau tangles, but some of the newest, most promising candidates are coming from the natural world in plant-based chemicals.
3. Poor Blood Flow to the Brain
As we age, blood flow to the brain may begin to decline.
Blood brings nutrients and oxygen to the cells. It’s also responsible for clearing out the garbage and toxic byproducts.
Think about it as living in a city.
Our houses are the cells, and the roads represent blood flow.
In order to get the water and food we need, we must build a road that connects our house to the rest of the city. We also need these roads for the garbage trucks to come and pick up the garbage we left out the night before.
If for any reason the road becomes blocked, we won’t have any access to food, and our garbage begins to pile up outside the house.
If this happens for too long, we will eventually die of starvation or from an infection from the rotting garbage.
It’s similar to the brain. If blood flow is bottlenecked for too long, the neurons will die of toxic overload and lack of nutrients or oxygen.
This is related to the pathological processes taking place with Alzheimer’s disease. The same amyloid-beta plaques that are neurotoxic also bind to blood vessels in the brain and reduce the ability of the blood vessel to exchange materials and clear things out. It also weakens the blood vessel wall and increases the risk of stroke. The risk of developing amyloid plaques on blood vessels is higher in people with more ApoE4 genetic inheritance.
Therefore improving blood flow to the brain is one of the primary goals of hospitals when treating the condition.
4. Glial Cell Dysfunction
Remember the garbage disposal cells we talked about earlier?
These are the glial cells.
They’re the most abundant cell type in the brain and for good reason.
They’re tasked with keeping the functional part of the brain, the neurons, working at their best – and they do that by fighting pathogens, removing dead neurons, keeping the neurons in place, bringing in oxygen and nutrients, and more!
As soon as the glial cells stop doing their job, the neurons will start to degrade, causing all kinds of issues with cognition. This includes Alzheimer’s disease or other forms of dementia.
The Apo enzymes are supposed to help glial cells and astrocytes to envelop and degrade amyloid-beta proteins before they become plaques. ApoE4 is the least efficient in carrying amyloid-beta to glial cells, thereby increasing the risk of developing Alzheimer’s dementia.
Anything that improves the health and function of the glial cells is theoretically likely going to go a long way in offsetting the processes behind Alzheimer’s disease.
5. Oxidative Damage
We all need oxygen to survive, but did you know it’s also the main reason we age?
Oxidative damage refers to a special type of chemical reaction known as “oxidation”.
Fitting name right?
Oxidation happens when molecules steal electrons from other molecules. When this happens, the molecules that had their electrons stolen start to degrade and fall apart. If enough molecules are affected on a cell, the cell may die.
When these molecules make up the outside of our nerve cells, this becomes a major problem.
Oxidative damage occurs whenever toxic compounds like amyloid-beta, lactic acid, heavy metals, or other free radical compounds are allowed to build up outside the cell.
Over time, oxidative damage may be a risk factor for Alzheimer’s disease.
Antioxidant support is a common method of protecting the brain, as well as every other organ in the human body. This is one of the strengths offered to us from the natural world, as some plants tend to be very high in antioxidant compounds.
Common Treatments for Alzheimer’s Disease
While no medication can stop Alzheimer’s disease, there are a few commonly used to slow down its progression. These can help the patient live more comfortably and prolong their independence.
Cholinesterase inhibitors (galantamine, rivastigmine, and donepezil) seem to prevent the breakdown of acetylcholine and work best for mild to moderate cases. These can provide some relief of symptoms and help control behavior.
N-methyl D-aspartate (NMDA) antagonists like memantine help those with moderate to severe Alzheimer’s disease maintain daily functions a little longer.
Since CBD can interact with certain medications, it’s important you talk to your doctor before combining it with over-the-counter or prescription drugs.
Summing it All Up: CBD and Alzheimer’s Disease
CBD oils may potentially offer an excellent array of benefits for the progression of Alzheimer’s disease, as suggested by early but exciting research.
The indicated effects of the oil are mainly preventative in nature, helping to slow the progression of the disease and improve the overall quality of life.
If you want to avoid the psychoactive effects, we recommend choosing a product that has less than 0.03% THC content.
But if you don’t mind the psychoactivity and live in a country or state where THC oils are legal, we highly recommend going with a product containing closer to a 1:1 ratio of CBD to THC for maximum benefits.