Comprehensive and Updated Research on CBD and the Pathways of Dementia and Alzheimer's
September 28, 2020
There's exciting new research recently on dementia.
Maybe, more importantly, there is a sea-shift in how dementia is viewed in terms of our immune system.
In fact, across the mental health spectrum of illnesses, immune response in the brain is coming into focus.
We'll look at all the research on this below.
Interestingly, this points to autoimmune or bacteria crossing the blood/brain barrier as potential causes which we'll explore below.
So many fascinating clues are pointing in this direction.
APOE4...the recently discovered gene which can carry risk for dementia?
Thus, the presence of the APOE4 gene may also regulate classical immune activation and the production of pro-inflammatory factors in a manner independent of protein concentration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782461/
Immune response.
We'll look at many such clues below including the amyloid plaques and fibrils that have long been a signature of the disease even though medications targeting them have failed...
Finally...how does CBD affect these pathways?
Here are the topics that we'll cover:
- An updated view on cause and mechanisms of dementia - The secret role of AB protein and amyloid
- Brain inflammation and dementia
- Immune response and dementia
- Is dementia an autoimmune disease
- The blood-brain barrier and dementia
- The gut barrier and dementia
- Serotonin's hidden role in the brain
- The estrogen effect on dementia risk for women
- Acetylcholine and dementia
- Genes tied to dementia
- Neurogenesis and BDNF and dementia
- CBD and the pathways of dementia
- How much CBD for dementia
- What's the best CBD for dementia
Let's get started. Lots to cover.
An updated view on cause and mechanisms of dementia - The secret role of AB protein and amyloid
First, the original concept.
Early researchers (including Alzheimer himself) noticed the deposits of amyloid (his word creation) for deposits in the brain associated with the disease.
Amyloid beta (AB for short) was thought to be a driver of the disease and much research on medicines focused on this pathway.
To no avail (yet).
In fact, when the ab load is reduced, the disease continues and in some cases, worsens.
Since then, there's more basic research on what AB actually does in the body and it's illuminating.
AB is part of a vast army of responders in our brain and nervous system to invaders.
Bacteria. Parasites. Anything that shouldn't be there in the brain.
It's just one tool in our innate immune response.
As researchers put it:
Recent evidence indicates a role for Aβ as an antimicrobial peptide (AMP), a class of innate immune defense molecule that utilizes fibrillation to protect the host from a wide range of infectious agents.
https://pubmed.ncbi.nlm.nih.gov/29504537/
Studies have found that AB is 100 times more potent than penicillin in its antimicrobial effects.
There's a brilliant review here.
https://www.youtube.com/watch?v=YkkAk_YA8O0&t=352s
In fact, new, highly sophisticated scans show that the Amyloid plaque actually surrounds the bacteria, punches holes in it, and entombs the pathogen in the brain.
Unfortunately, too much of this activity can damage surrounding healthy tissue.
This is always the case with an immune response.
Collateral damage is high and the brain's immune response is especially strong given the importance of the real estate.
Again, check out the youtube Ted talk above...fascinating work.
Now, the question is whether this autoimmune where our system is overreacting or if there's an actual infection occurring .
Maybe a mixture of both...initial infection and resulting resistance to immune response.
Just understand that this is war and our brain tissue is the battleground.
There will be civilian casualties.
Do we have supporting evidence for this?
We would expect to see brain inflammation as a result.
Let's go there now.
Brain inflammation and dementia
Inflammation has a bad meaning in the common culture but that's not entirely true.
Chronic inflammation is bad.
Inflammation is just a response of our immune system to bad entities. It's how we fight the good fight to stay alive.
If the above pathway is correct and dementia is the collateral damage to an immune response war in our brain, we would expect to see telltale signs.
Inflammation markers.
Newer research is showing this effect from many different angles.
We predicted the link between inflammation in the brain and the build-up of damaging proteins, but even we were surprised by how tightly these two problems mapped on to each other,
https://www.sciencedaily.com/releases/2020/03/200316204635.htm
A look at c-reactive protein (a marker of inflammation which you can test easily):
They found that the 90 participants who had chronic inflammation also had the most white matter damage in the brain. White matter is responsible for carrying information between nerve cells and damage can result in cognitive decline and lead to dementia.
https://www.alzheimers.net/chronic-inflammation-linked-to-dementia
They found that most of the damage was tied to chronic inflammation during mid-life.
What about anti-inflammatories? Any effects?
Yes, if used during mid-life:
considerable reduction in risk of Alzheimer's disease in those who had taken these drugs for two years or longer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1126777/
Not so much later in life with actual onset.
Let's introduce cytokines...the specialized assassins of our immune response.
Long-term studies of dementia found clear associations:
A recent meta-analysis study reported significantly higher levels of the proinflammatory cytokines TNF-α, IL-6, IL-1β, IL-2, and IL-18 in peripheral blood samples of patients with Alzheimer's disease (AD) compared with a control group
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252389/
These are immune responders. They are designed to respond to intruders!
Let's now look at the generals of our immune response.
Immune response and dementia
So...who are the players?
Let's first introduce microglia...our immune response controllers.
Hyperactivation of microglia is tied to a host mental health issues including schizophrenia, bipolar, autism, depression, anxiety, and more.
Check out:
See why the immune response is the new exciting addition to research and mental health?
What about microglia and dementia?
Just this...
Our data indicate that major Alzheimer risk factors, such as age, sex and genetic risk, affect the complex microglia response to amyloid plaques in the brain
https://www.sciencedaily.com/releases/2019/04/190430105740.htm
Read that back over. It means that all the other risk factors converge in one area...microglia activation differences.
The linchpin!
You'll understand why when we look at what microglia do.
First, they initiate the inflammatory response (cytokines and other weapons above) in response to infection.
Keep in mind that the microglia can be "primed" even by an early infection in utero from your mother.
This is the key connection with certain mental health issues like autism and schizophrenia.
The more important piece perhaps is the removal of waste material.
Microglia remove the amyloid plaques by literally eating them...engulfing them (call phagocytosis - from the Greek word "to eat") for removal.
Remember that amyloid-beta build up in the form of plaques is a hallmark of the disease and very destructive to surrounding tissue.
AB literally leaches out bleach (the result of a chemical process) to kill bacteria.
Bleach breaks apart organic material like no other including neurons.
Let's introduce APOE4.
It's a known genetic trigger for dementia risk.
What's the association with microglia?
Very recent research found direct connections between different gene variants of APOE and microglia interaction with amyloid plaques:
We observed that microglial coverage of plaques is highest in male APOE3 mice with significant reductions in coverage observed with both APOE4 genotype and female sex.
https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-019-0729-z
Turns out that APOE4 is highly involved in immune response!
Thus, the presence of the APOE4 gene may also regulate classical immune activation and the production of pro-inflammatory factors in a manner independent of protein concentration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782461/
So...immune response dysregulation is now a driving factor for the dementia process and risk:
In the brains of both AD patients and mouse disease models, microglia are found closely associated with the amyloid plaques and exhibit an 'activated' proinflammatory phenotype
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653290/
It appears that microglia cells get stuck "on" and actually create more harm than good.
But in Alzheimer's, research suggests microglia become overactive, increasing their production of cytokines and simultaneously clearing less.
https://www.alzdiscovery.org/news-room/blog/inflammation-the-driver-of-alzheimers-disease
The question is why?
What is setting the immune system off so much and chronically?
Let's dig deeper, shall we?
Is dementia an autoimmune disease
So, we know the immune response is critical to the process of dementia.
Response to what?
Actual bacteria or infection? Foreign chemicals?
Or is the immune system hyperactivated and attacking the brain?
This is the basis for autoimmune...just the target is different.
- Arthritis - joints
- Diabetes type 1 - islet cells
- Asthma - lung tissue
What if the target is the neurons in the brain?
First, we know there is a tie between other immune diseases like rheumatoid arthritis and dementia risk:
Among the patients with ARDs, the subgroups with rheumatoid arthritis, systemic lupus erythematosus, and Sjögren syndrome (SS) were associated with a significantly higher dementia risk
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755737/
Then, there's the gender effects of both.
Women are harder hit by both at comparable ratios:
Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7
We'll speak to the estrogen effect below.
There's the question of whether the initial autoimmune disease is causing the immune response to heighten or if they both share an underlying issue.
What about the tie between prior experience and DNA expression?
This is very exciting (and new).
They are called epigenetic tags.
Little pieces of info from prior immune response that get added to our microglia cells.
This may help explain the connection between dementia/Alzheimers and prior infection, gum disease, other autoimmune illnesses, etc.
https://blog.alzheimers.org.uk/research/inflammation-and-dementia/
There is even the study where symptoms were reversed in mice by blocking a specific part of the immune system with a common anti-inflammatory, mefenamic acid.
"Our research shows for the first time that mefenamic acid, a simple Non-Steroidal Anti Inflammatory Drug can target an important inflammatory pathway called the NLRP3 inflammasome, which damages brain cells."
What if the immune system is correct and we're under constant (chronic) attack by bacteria or chemicals?
We need to visit or primary defense against these entities….the blood-brain barrier.
The blood-brain barrier and dementia
We have a very tightly regulated barrier that decides what can enter the brain and what cannot.
The brain obviously needs nutrients and a host of different substances from the blood in order to function.
What if a bacteria or noxious chemical is hitchhiking?
This barrier is governed by the immune system (astrocytes to be specific) but it's not full-proof.
Remember the managers of the blood-brain barrier, astrocytes? Are there clues there with dementia?
Yes!
Remember the APOE4 risk above?
People who carry the gene variant APOE4 are at higher-than-average risk of developing Alzheimer's disease. It emerges that this variant is linked to defects in the blood-brain barrier and subsequent cognitive decline.
https://www.nature.com/articles/d41586-020-01152-8
Here's the interesting point…
The degree of disruption to the BBB correlates with the degree of cognitive dysfunction that a person experiences.
The more breakdown in this barrier, the worst the symptoms.
No wonder the immune response has to go on high alert in the brain; there's a hole in the wall!
Remember how astrocytes are in charge here?
Astrocytes, the supporting cells of the brain, could play a significant role in the pathogenesis of Alzheimer's disease (AD), according to a new study. This is the first time researchers discovered a direct association between astrocytes and AD.
https://www.sciencedaily.com/releases/2017/11/171117103740.htm
So, the question to ask is this…
What causes a breakdown of the blood-brain barrier?
Many things can:
- Chronic stress (see CBD and stress )
- Oxidative stress (see CBD and oxidative stress )
- Obesity
- Trauma
- Various drugs and chemicals
Let's revisit the autoimmune angle from above.
If the blood-brain barrier is constantly dealing with an infection, this would also lead to issues.
But infections from where?
We now have to travel to the gut!
The gut barrier and dementia
There's a much more powerful barrier that lies at the heart (and beginning) of all autoimmune diseases.
Every time you eat, billions of bacteria, viruses, and other microbes are hitching a ride.
There's no way around it. We're inundated with bacteria.
Luckily, we have an entire biosystem living in our gut composed of mainly friendly (hopefully) bacteria, yeast, and other life forms.
This is the microbiome and the newest star in research for health and mental health!
Check out CBD and probiotics for anxiety . The review of CBD and autism is fascinating on this front.
We have a powerful barrier there which lets good things (nutrients, etc.) through and keeps out bacteria and other pathogens.
If you really think about it, this is the most vulnerable area to the outside world and the trillions of potential intruders.
It's really the primary way into our body since our skin has its own layer of protection.
Talk about the Trojan horse!
The breakdown of this barrier is key to autoimmune as a constant stream of bacteria that breakthroughs will elicit an immune response throughout the body!
In fact, very sophisticated scans of plaque deposits in arteries turned out to have DNA of bacteria!
Cholesterol is just the "spackle" the body uses to entomb bacteria and repair damage from the inflammation response in the arteries.
You can't have arterial plaque without inflammation regardless of cholesterol levels.
We digress!
What about the gut barrier and dementia? Any connections?
Think of a line of dominos...gut barrier breakdown may be the first domino:
Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326209/
See the cascade?
- Gut bacteria go astray.
- Gut barrier breaks down
- This leads to the breakdown of the brain barrier
- Inflammation response and eventual damage follow.
So...let's start with the gut bacteria?
Any clues there?
Moreover, significant quantitative and qualitative changes of gut microbiome have been reported in patients with Alzheimer's disease.
https://www.frontiersin.org/articles/10.3389/fcimb.2020.00104/full
You can't underestimate the function of our microbiome.
Most of your serotonin (our primary neurotransmitter manager of behavior and mood) comes from the gut.
These bacteria drive many neurotransmitters and even BDNF, our brain's fertilizer (more on that below).
Just an example (out of a sea of interactions).
These findings indicate that CB treatment could attenuate microglia-mediated neuroinflammation via regulating the GM-gut-brain axis, which is mediated by the metabolite butyrate.
https://pubmed.ncbi.nlm.nih.gov/31835282/
Let's translate, please.
A certain bacteria in our gut (Clostridium butyricum) calmed down the microglia inflammatory response.
This is the exact mechanism listed above for dementia risk and process.
Check out CBD gut barrier or CBD and neuroinflammation to really get deep into the research.
Most of our serotonin is made in the gut.
Let's look at serotonin directly and learn about its hidden role in the brain.
Serotonin's secret role in the brain for dementia
There's been a known connection:
Previous studies from Johns Hopkins and other centers have shown that people with Alzheimer's disease and severe cognitive decline have severe loss of serotonin neurons
https://neurosciencenews.com/serotonin-levels-dementia-7293/
Here's where it gets interesting.
Serotonin does many things in the brain and one of them is to support our repair process.
Specifically, serotonin boosts BDNF, our best friend with dementia and most mental illness.
This especially true after...stress!
In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090852/
To translate...when they block serotonin (H5T) pathways, BDNF did not kick up the way it should after stress.
We've covered this in detail at our CBD and neurogenesis , why SSRIs really work , and CBD and BDNF .
BDNF and neurogenesis might be the rising stars over the next decade for mental health.
If stress and the immune response is literally killing off brain tissue, the repair mechanism becomes incredibly important.
We'll cover this in more delta below but let's turn our attention to estrogen of all things.
The estrogen effect on dementia risk for women
Why do women get hit so hard by dementia risk?
More importantly, why do those risks explode higher after perimenopause?
The answer should be obvious...female hormones progesterone and estrogen have powerful protective effects across the body and brain!
Check out CBD and perimenopause brain fog to get to the bottom of it.
It turns out that estrogen is a primary driver of serotonin which as we now know from above, directly drives BDNF...our most powerful repair and rebuild chemical in the brain.
Goodness.
We did a full review on estradiol (our primary estrogen) supplementation and safety since the 2002 WHO report incorrectly scared millions of women and significantly increased their risk for dementia.
Serotonin and estrogen aren't the only players though. In fact, there's one directly tied to dementia risk.
Acetylcholine.
Acetylcholine and dementia
The newest research is pointing directly to acetylcholine.
You may not have heard of it but it's key to the progression of dementia.
Check out our full review of Acetylcholine here.
In fact, many drugs rip acetylcholine from the body and they have been shown to increase dementia risk.
- Antihistamines like Benedryl and Tylenol PM
- Statins
- SSRIs
There's a good explanation and list of drugs here:
https://www.beingpatient.com/anticholinergic-medications-increase-dementia-risk/
Harvard has a good review of the Benedryl study here:
Newer research is really showing that acetylcholine is the linchpin for dementia!
Let's take a detour to genes!
Genes tied to dementia
Are there genes tied to dementia risk? Do they fit the landscape we described above with inflammation, immune response, and the like?
We already mentioned the APOE4 gene above.
It turns out that this intersects with an immune response directly in terms of dementia risk.
Look a the newest research:
In the past years, genome-wide association studies (GWAS) identified over 25 genetic loci that robustly associate with risk of late-onset Alzheimer disease (LOAD); many of these, relate to neuroinflammation and are preferentially or exclusively expressed in microglial cells, implicating microglia reaction as not only a consequence of Alzheimer's but likely also a cause.
https://www.frontiersin.org/articles/10.3389/fnagi.2019.00233/
Goodness…microglia. Neuroinflammation.
More importantly… "Likely a cause."
What about BDNF (brain's fertilizer)?
Just this…
Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763800/
So….we have two sides of the coin with dementia.
- An increased damage side - inflammation, oxidative stress, immune hyperactivate
- A decreased repair side - serotonin, BDNF, estrogen
Let's turn our attention to the repair side since we can definitely affect that part.
Neurogenesis and BDNF and dementia
This may be the most important part of this entire article.
We've already danced around it above (serotonin, estrogen, etc.).
Estrogen drives serotonin. Serotonin drives BDNF.
BDNF is the star of the show!
In fact, when they look at the new cutting-edge research on mental health including depression and anxiety, all roads lead to BDNF.
SSRIs? Boost serotonin and BDNF (till they don't when your body builds tolerance.
In fact, cut out BDNF and SSRIs lose their antidepressant effect. (see CBD versus SSRIs).
Psilocybin from magic mushrooms? It's an explosion of BDNF. Check out psilocybin and mental health here .
Implications there for depression, PTSD, anxiety, addiction, and a host of issues.
We can even go more mainstream.
Exercise and mindful meditation...the pillars of reducing dementia risk?
BDNF. See exercise and meditation for neurogenesis to see the studies.
Dementia's signature is a loss of brain mass. This implies too much damage or too little repair.
Look at this little piece regarding BDNF:
BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763800/
Read that back over.
All the other triggers...age...gender...education...and other brain-related issues were leveled when BDNF levels were compared.
That's wild!
- BDNF drops as we get older so that makes sense.
- We already showed how estrogen drives BDNF so that makes sense.
- Education must drive BDNF pathways to grow the brain.
- Neuropathologies?? Goodness...this implies that BDNF drives those as well!
Finally, let's jump to CBD. Thank you for your patience!
CBD and the pathways of dementia
We've covered a lot above.
Let's now backtrack and see how CBD affects these different pathways and then look at CBD and dementia directly.
We'll cover these topics:
- CBD and immune response for dementia
- CBD and brain inflammation for dementia
- CBD and brain blood barrier for dementia
- CBD and gut barrier for dementia
- CBD and oxidative stress for dementia
- CBD and microglia for dementia
- CBD and neurogenesis for dementia
- Research on CBD and dementia
Let's get started.
CBD and immune response for dementia
We now know that amyloid is a specialized assassin for bacteria in our brains.
This is squarely in our immune response arsenal.
What does CBD do for the immune response? Specifically, in the brain?
We've covered this in detail at our CBD and neuroinflammation but some of our favorite takeaways.
One study blocked an artery to the brain for mice and of course, there was an explosion of inflammation as a result.
CBD's effect were profound:
Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO.
https://www.ncbi.nlm.nih.gov/pubmed/27889412
Read that back over.
BBCAO is just the procedure of blocking the artery.
CBD protected the brain from white matter injury. You remember...the tracts of communication between brain areas?
The reason why paranoia, irritation, and other symptoms result from dementia.
Glia response speaks to the microglia we discussed above...our sentinels of brain immune response.
In general, CBD is immune-suppressive when it's hyperactivated.
On the flip side, it can actually boost immune response in situations where it's running too low.
Let's zero into the beta-amyloid specifically since it's a unique signature of dementia.
CBD and beta-amyloid for dementia
There is specific research on this and they even know what pathway is involved.
Here's the summary:
Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta-amyloid expression in SHSY5YAPP+ cells through PPARγ involvement
https://pubmed.ncbi.nlm.nih.gov/24288245/
Let's decipher that, shall we.
There's a chain of chemical activity that leads to amyloid-beta production.
CBD interfered with this chain to reduce beta-amyloid loads.
The SHSY5YAPP is a special cell designed to overly express amyloid-beta that's used in dementia research.
PPAR is one of the pathways in the body that CBD directly affects.
There's been a known potential protective effect of anti-inflammatories for dementia.
Scientists now think this is because they stimulate the PPAR pathway directly.
A number of epidemiological studies demonstrated that NSAID treatment reduces AD risk by as much as 80% and it was suggested that these effects arise from the ability of these drugs to stimulate PPARγ and to inhibit inflammatory responses in the AD brain
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263458/
In fact, there's a lot of activity on drugs that stimulate pPAR activity for dementia.
CBD is a direct agonist (booster) of PPAR as per this chart:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345356/table/T1/
We'll cover more in the dementia-specific area below.
What about the result of immune response...inflammation?
CBD and brain inflammation for dementia
Remember, inflammation is a response of our immune system.
The easiest way to look at this is with cytokines...the little assassins of our immune response.
Remember that they are elevated in people with dementia:
The involvement of cytokines in dementia is supported by studies (11–13) showing that the levels of pro-inflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1α, IL-1β, IL-6, and IL-8] are altered.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252389/
What does CBD do there?
The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-α were determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels.
https://www.hindawi.com/journals/mi/2015/538670/
Interesting. What's the deal with IL-10? Why didn't that come down as well?
It turns out that IL10 is anti-inflammatory!
And CBD's effect:
We and others have shown that CBD upregulates the anti-inflammatory cytokine IL-10 [71,78,130], the immunoregulatory genes in autoimmune T cells mediating EAE/MS [72,73], and induces inhibitory cell phenotypes resolving inflammation, including myeloid-derived suppressor CD11b+Gr1+ cells [131] and CD4+CD25+LAG3+ T cells [72
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578059/
Goodness. A slew of anti-inflammatory effects.
The key words there are "resolving inflammation."
Studies found on dementia that the process of resolving inflammation was impaired.
So...these sections have all been about calming inflammation once started.
What about preventing it from happening to begin with?
Let's go to the barriers.
CBD and brain blood barrier for dementia
Let's cut to the chase:
Cannabidiol protects an in vitro model of the blood-brain barrier from oxygen‐glucose deprivation via PPARγ and 5‐HT1A receptor
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761095/
There's PPAR again and 5HT is serotonin.
There have been studies of CBD's effect on the blood-brain barrier breakdown (alliteration at its best) from inflammation and even stroke.
The summary:
Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150944/
Ischemia is technical for stroke.
Interestingly, CBD is able to cross the blood-brain barrier. Otherwise, this whole discussion would be a waste.
Unless we dig deeper into the root of inflammation.
All roads lead to Rome and the gut is our immune response to Rome.
Let's travel there now.
CBD and gut barrier for dementia
You have to cut the leak off at the source.
Our gut's interaction with the world sends inflammatory signals through our immune system but more importantly, it's where pathogens are likely to enter.
This whole area of discovery is exciting and new that we covered it at our CBD and gut barrier or CBD microbiome reviews .
Just look at one example of crosstalk between the gut and the brain:
Look at the brain alone:
Microbiota regulate 5-HT1A, BDNF and NMDA expression (Sampson et al., 2016), and experimental transplantation of the microbiome of Parkinson patients to mice was demonstrated to increase their motor deficits, supporting the finding of a pro-inflammatory dysbiosis (microbiome imbalance) in that disorder
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200872/
5HT is serotonin (see CBD and serotonin ). BDNF is our brain's fertilizer. NMDA is where glutamate (our brain's gas pedal) does its primary work.
Goodness. Parkinson has some interesting correlations with dementia (neurodegenerative, inflammatory, acetylcholine!).
So...back to protecting the gut barrier.
We'll get right into since there's lots of research at the reviews above:
cannabidiol accelerated the recovery from cytokine-induced increased permeability; an effect sensitive to CB(1) receptor antagonism.
https://www.ncbi.nlm.nih.gov/pubmed/21745190/
Researchers now know that a slew of very common drugs damage the gut lining and/or the microbiome tasked with maintaining it (and actually making up the first layer of it).
NSAIDs, anti-inflammatories are a big culprit but by no means the only one.
Let's turn a different type of stress. Oxidative stress.
CBD and oxidative stress for dementia
Oxidative stress refers to little bits of oxygen in various forms that are produced as a waste product of making energy (primarily).
They are like little molecular scissors that indiscriminately cut whatever they come in contact with if not dealt with.
Neurons. Brain barrier. You name it.
As for dementia?
Oxidative stress (OS) has been demonstrated to be involved in the pathogenesis of the two major types of dementia: Alzheimer's disease (AD) and vascular dementia (VaD).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537746/
We've covered this in detail at our CBD and oxidative stress or CBD and glutathione.
Glutathione is our primary antioxidant in the body.
Think of oxidative stress as a representation of damage.
What about CBD?
CBD has been shown to have potent actions in attenuating oxidative and nitrosative stress in several human disease models, although the exact mechanism is unclear.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/
And where is this relevant according to the researchers?
These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer's disease, hypertension, metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.
It's interesting that diabetes, heart disease, high blood pressure, etc. are all known co-occurring issues and risks for dementia.
Check out the research and also consider NAC (N Acetyl Cysteine) .
We have a full review of NAC here but new research on NAC and dementia is very interesting.
Essentially, NAC helped to block the accumulation of plaques:
https://www.eurekalert.org/pub_releases/2021-03/chop-crf031921.php
What about CBD and immune hyperactivation?
CBD and immune response for dementia
The immune system is very complex so we'll touch on elements specific to dementia.
As we saw above, the Amyloid beta particles are actually members of the immune system in response to bacteria.
Researchers are now pinpointing the mechanics of how AB accumulates.
Part of it the process involves DNA being "turned on" to activate production. This leads to "gliosis" or the activation of microglia and astrocytes (brain immune responders).
Look at CBD's effect specifically here:
Therefore, these results imply that CBD is able to reduce Aβ-induced reactive gliosis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289988/
The Amyloid-beta sends signals to microglia to unleash the hounds (various immune assassins) which then cause the collateral damage to brain tissue.
Two powerful players (of many) is NO and IL-1B.
Look at CBD's effect on this signal:
n addition, CBD reduced both iNOS and interleukin-1β (IL-1β) protein expression and the related NO and IL-1β release
Again, this gets complicated fast but let's zero in on the microglia since they run the show.
CBD and microglia for dementia
If microglia (immune commanders) are too active for long stretches of time, this results in damage.
We see this across a range of mental health issues and the trigger can even be an early infection in utero by the mother.
As researchers put it:
Hyperactive microglia, a common feature of these neurodegenerative diseases, secrete a number of pro- and anti-inflammatory cytokines, chemokines, glutamate, prostanoids, neurotrophic factors, and a range of free radicals that provide a milieu for oxidative stress.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386505/
After all, our original immune makeup is passed down from the mother.
Hyperactivation is the key term as damage results from this state.
It's like arthritis of the brain!
There's a lot of detail at this review below but the net take away for CBD and Alzheimer's:
In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102548/
AD is Alzheimer's Disease.
Check out CBD and microglia to learn more.
We've spoken about the damaging side till now. Oxidative stress. Microglia hyperactivation. Cytokines.
That's only half the equation. What about the repair side?
CBD and neurogenesis for dementia
This may be the most important piece. Remember BDNF (our brain's fertilizer), serotonin (the driver of BDNF), and neurogenesis?
BDNF levels were primary determining factors for dementia when gender, age, neurological diseases, and education were taken into account.
Think about that!
Even though women are hit with dementia at a much higher rate (we now know it's from a loss of estrogen), BDNF's effect still reigned supreme.
i.e. an older woman with higher levels of BDNF had a much lower risk of dementia.
Neurogenesis is the pathway where all the damage from immune over-reaction occurs .
It's frantically trying to keep up with microglia that have run wild.
Amyloid beta (an immune responder) literally manufacturers bleach and creates long needles (fibrillation) that puncture what they come in contact with (hopefully bacteria).
Repair is needed after the battle.
We have a full review of CBD and brain repair here but some key takeaways.
Let's cut right to the chase for dementia:
Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230631/
Goodness. AB is amyloid-beta. Hippocampus is the seat of memory and mood control in the brain.
The hippocampus is especially vulnerable to damage since it's so dynamic (memory changing all the time).
In fact, it's size can point to early risk:
The size of the part of the brain known as the hippocampus may be linked to future dementia,
https://www.sciencedaily.com/releases/2010/11/101116072756.htm
We covered CBD, exercise, and mindful meditation for hippocampus neurogenesis separately since it's so important.
Yes, exercise and mindful meditation are both powerful tools there.
Check out CBD and BDNF or CBD and neurogenesis for more detail.
Let's jump to CBD and dementia research specifically.
Research on CBD and dementia
There's a good table of various studies on CBD and dementia here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289988/table/T1/
These are mainly studies on mice models of dementia which are very positive.
Currently, there are multiple trials looking at CBD for dementia directly.
It's a shame were in 2020 and till underway since we see all the components above and have really good options for dementia elsewhere.
Other studies have looked at CBD for symptoms of dementia such as irritability, sleep disruption, etc.
Most of these studies are looking at CBD in ratio to THC which is not great based on our research.
If anything, CBD counters much of the pathways stimulated by THC (for the better).
See why CBD is a must if you use cannabis or CBD versus THC.
The ratios were generally 2:1 CBD to THC and the results were very positive.
You can skip down to "Changes in specific symptoms" as this review study here:
https://www.ncbi.nlm.nih.gov/books/NBK546328/#
One example:
One cohort study included in the systematic review3 found significant improvements (P < 0.05) in aberrant vocalization, motor agitation, aggressiveness and resting care as assessed on PAS among 40 patients, after treatment with dronabinol at a mean dose of dose of 7.3 mg/day for a mean duration of use of 16.88 days.
These are all important aspects of daily quality of life for patients but maybe more importantly, for caregivers.
We covered CBD and paranoia here which is a known issue with dementia.
The list of symptoms effects are profound:
- Vomiting
- Screaming
- Pain
Such as this result dealing with pain and psychotic behavior:
Also, two patients (20%) stopped all morphine within three months, one patient (10%) decreased morphine by two-thirds in two months, and one patient (10%) stopped two antipsychotic medications after one month.
Check out CBD and psychosis or CBD and pain for more info.
Again, there are full-blown clinical trials both in Europe and the US for CBD and dementia in a controlled, well-designed study.
We'll add those studies as they come online.
Let's get to practical questions.
How much CBD for dementia
We can actually look to research here….especially on the neurogenesis piece.
Studies have shown a curve-like response for neurogenesis with CBD dosage.
It appears to peak around 300 mg per day. Beyond that, it goes down as another pathway is triggered.
For more serious issues like psychosis or panic attacks, the research points to higher amounts of about 600-800 mg.
In our review of CBD and addiction , we referenced studies on opioid withdrawal which were at these higher levels.
This would speak to a higher level to start during a transition and then 300 mg longer term for neurogenesis and immune system balancing.
In addition, powerful tools with research:
- Berberine - protects the gut lining
- NAC - supports the antioxidant system and captures excess glutamate
- Turmeric - powerful anti-inflammatory and gut mediator
- Acetylcholine - direct correlation with cognitive ability and dementia (hence the risk with antihistamines which rip acetylcholine) - you can get CDP choline or eat eggs!
These tools along with CBD may make for interesting allies.
What about the type of CBD?
What's the best CBD for dementia
First, the basic requirements which many companies don't meet:
- Organically grown in the USA at an FDA registered farm
- CO2 processed
- 3rd party tested
- No THC
- No Pesticides
- No Solvents
- No Heavy metals
- No Mold
- No Bacteria
We actually test our oils twice since the whole family uses it.
Those are just the basic requirements.
A note on the question with THC.
The issue with THC is that it builds tolerance. THC mimics anandamide, our naturally occurring cannabinoid in the brain.
The brain sees this artificial bump and reduces our naturally occurring CB1 (the receptor they both work at) activity as a result over time.
This means we have less and less of the very thing we took THC for to begin with!
Of course, there are other issues such as histamine response, anxiety, psychosis, etc depending on a person's makeup.
The tolerance is the bigger issue.
CBD does not work that way...in fact, it works like a feedback mechanism in key pathways which is why it offsets the negatives of THC.
Then there's the question of CBD isolate versus CBD full spectrum .
Here's the deal...40-60% of the population has histamine issues. An allergic response.
This goes up as we get older and for women which happens to mimic the dementia risk profile.
Histamine response is part of our immune response so we don't want to trigger it.
Many people have histamine responses to full-spectrum CBD (allergic, anxiety, stomach issues, etc) that go away with CBD isolate.
That's why we focus on CBD isolate. Just look at the reviews and you'll see many who have the same response.
CBD by itself will calm histamine and immune over-response. Full-spectrum...may go the other way.
More importantly, all the research is about CBD itself. We focus on research otherwise, it's just marketing.
Then there's the question of cost.
If research is showing peak neurogenesis at 300 mg per day, we have to be able to afford this.
The key there is cost per mg of CBD.
We purposely price our CBD at around 2-3 cents per mg of CBD for our 6000 mg bottles before discounts up to 30%.
If you read our story here , we've been there at the hands of brutal perimenopause.
The founder also has a gene for acetylcholine (rated an "F") and the APOE4 variant so dementia risk is important to us.
We supplement choline and use CBD along with NAC, berberine, and more as protective measures until Crspr can switch out those genes!
Also, exercise and mindful meditation (check out the Calm app).
Be well. Take care of each other. Take care of yourself.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.