A person reached via chat to check on research regarding CBD and Parkinson's.
With over 1 million+ word of research on CBD across multiple pathways, we haven't done a deep dive on Parkinson's.
Yet.
We quickly scanned NIH studies from her request and there's some fascinating research out there now.
Most of it is really new (last few years).
Just wait till you see the study where researchers do a fecal transplant from a person with Parkinson's to germ-free mice...and the mice develop movement disorders!
We'll get into the gut inflammation piece in-depth!
In fact, there's research on other tools as well we can look at.
We can use these till new CRSPR treatments (fascinating one below) come online over the next 5-7 years.
Let's get to it!
We'll cover these topics:
- A quick look at what causes Parkinson's
- Protein mimicry and Parkinson's
- The Parkison's Dopamine connection
- The new Parkinson's tie-in with Acetylcholine
- Gut inflammation and Parkinson's
- The blood-brain barrier and Parkinson's
- Brain inflammation and Parkinson's
- Research on CBD and Parkinsons
- Other tools for Parkinson's (with a focus on NAC and Choline)
- How much CBD for Parkinson's
- What's the best CBD for Parkinson's
Let's get started.
A quick look at what causes Parkinson's
We're all familiar with the symptoms of Parkinson's...basically a loss of voluntary muscle control which displays as shaking and a range of involuntary movements.
But what's actually going on behind the scenes?
This is very important as we move further down into specific pathways especially in regards to how CBD affects those pathways later on.
There's a specific type of neuron in a specific brain area called the substantia nigra that comes under attack.
This neuron is in charge of producing dopamine, a powerful neurotransmitter that manages our reward circuit.
Anything that elicits active engagement including...movement!
Yes, to go get that game or berry (or promotion), the first step is movement and so dopamine governs this whole "motivation" circuit.
WIth Parkinson's, these neurons are systematically destroyed which leads to a loss of dopamine.
Dopamine is in charge of muscle control and the outcome is...unfortunately, very well-known and heartbreaking.
If want to jump the gun and really zero in on the root, it would be this:
Parkinson’s Disease pathogenesis is also thought to involve down-regulation of nuclear receptor Nurr1 in microglia and astrocytes, leading to increased production of mediators such as chemokine CCL2 that may promote apoptosis of dopaminergic neurons
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524694/
Let's translate, please.
Essentially, an immune response is causing damage to specific neurons that make dopamine.
That's the snapshot but what follows below is the whole process that leads to this.
Remember that CCL2 for CBD's section below...fascinating!
Stay with us because this is going to get very interesting based on new research.
Why only these neurons? That's very peculiar!
Protein mimicry and Parkinson's
The entire field of autoimmune has turned a corner with the discovery of protein mimicry.
Here's the basic scoop.
Different species of bacteria have specific proteins on their surface.
These proteins act like signatures for our immune system which has a library of known suspects, to find and apprehend known trespassers in our body.
The problem is that we're all (humans, bacteria, viruses, etc) made from the basic chemical soup.
If the bacteria protein looks similar to a protein we have on one of our cells, the immune system can misrecognize it and attack!
That's autoimmune folks.
Have a history of strep throat? Your risk for psoriasis goes way up (see CBD and psoriasis).
Dementia? Amyloid-beta plaques are actually little immune assassins (equal opportunity destroyers).
Check out CBD and autoimmune to learn all about it but back to Parkinson's.
There's interesting new research on this front!
Three areas come to the front:
- Nasal biome
- Gut biome
- Vagus nerve
The gut and mouth are really the main drivers.
The make-up of bacteria in the gut and mouth have shown significant differences:
Through comparative analysis, significant difference in beta diversity of oral microbiota was found between PD patients and control groups.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045475/
And the gut??
They demonstrated that PD patients possessed significantly increased abundance of Akkermansia sp. and Prevotella sp. in gut microbiota compared with healthy controls.
There's a new kid on the block with Parkinson's called α-synuclein.
This is a specific protein that now lies at the heart of Lewy Bodies which accumulate in the besieged neurons.
What about viruses like Herpes and Epstein Barr?
First herpes:
We have investigated on the role of molecular mimicry between HSV1 and α-synuclein that could foster the progression of PD. The antibody response against homologous peptides in PD patients and healthy controls was evaluated, showing that these antibodies are highly prevalent among PD patients to healthy controls.
https://pubmed.ncbi.nlm.nih.gov/26857504/
So, Herpes simplex 1 virus has a similar protein to a-synuclein. This triggered an immune response as a result.
Epstein Barr?
Specifically, we have shown evidence for molecular mimicry between the C-terminal region of α-synuclein and a repeat region in the latent membrane protein 1 encoded by EBV.
https://pubmed.ncbi.nlm.nih.gov/24726430/
To translate, there's a portion of the α-synuclein protein that looks like a section of an Epstein Barr virus protein.
Again..this is all new research in the last few days.
Outside of genetic issues (malformation of the α-synuclein protein), why do people get Parkinson's later in life?
The immune system ages and loses management over previously exposed-to viruses.
Dormant viruses.
Another connection with viruses is that mitochondria, our cellular power plants, start to malfunction.
A new set of studies look at how these dormant viruses compete for the cellular machinery that the mitochondria use.
This leads to fascinating clues such as:
Spanish flu - The studies showed the flu survivors had up to three times the risk of developing Parkinson’s disease compared to someone who didn’t get the flu
More recently, up to 50 percent of those surviving infection with West Nile virus and nearly 25 percent infected with Western Equine Encephalitis virus develop symptoms of Parkinson’s disease
https://www.galvnews.com/health/free/article_55d8f75a-e768-5df0-b32d-c49e1a2275f9.html
Fascinating!
Survive a nasty virus and the risk for Parkinson's explodes.
There's an important take-away from this we can focus on.
The immune system or inflammatory response needs to be "managed".
Part of this process is called autophagy which is how the immune system gets rid of bad players such as the misshapen Sinuclean proteins.
Put a bookmark next to that for CBD.
Okay...we can quickly fall the rabbit's hole but it is fascinating to look at what modern research is showing.
Let's move upstream to the resulting effects from this cellular and immune havoc.
The Parkison's Dopamine connection
This part was first understood and has been for years now.
The net effect of the loss of the substantia nigra neurons is a reduction in dopamine.
In fact, most of the current treatments for Parkinson's revolve around boosting Dopamine such as L Dopa or even the new brain implants.
Dopamine is a powerful pathway...integral really.
When you boost it with the likes of L Dopa or Sinemet, you can see a push-back effect:
DNA methylation causes L-DOPA to stop being effective after a few years, instead giving rise to dyskinesia — involuntary jerky movements making life even harder for patients.
Dyskinesia is spastic, uncontrollable movements.
This tolerance effect has been known since 1993:
The duration of response after discontinuing the long infusions was briefer than after discontinuing the short infusion, suggesting the development of tolerance.
https://pubmed.ncbi.nlm.nih.gov/8474479/
We'll touch on CBD's effect on dopamine below but it's a very different approach.
We have a full review of CBD and dopamine here.
Just know that a reduction in dopamine in the brain is at the heart of the symptoms.
Let's move to the new exciting player. Acetylcholine.
The new Parkinson's tie-in with Acetylcholine
Acetylcholine is another powerful neurotransmitter.
It's the master of the parasympathetic nervous system or the "rest and digest" system.
This is in opposition to the "fight or flight" system so you get a good sense of how it feels.
Acetylcholine delivers both a calm and alert effect which is why so many people self-medicate with nicotine which fits right into the acetylcholine receptors.
Remember that we mentioned the Vagus nerve up above but never really explained it?
This is where acetylcholine is produced and it's the link between your two brains: the brain in your head and the vast nervous system (yes, actual neurons) of the gut.
So...dopamine was the supposed star of the show but newer research is pointing to acetylcholine.
Such as:
Atrophy of the Vagus Nerve in Parkinson's Disease Revealed by High-Resolution Ultrasonography
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170613/
We would expect a knock-on effect in acetylcholine from this.
Concomitantly, and as demonstrated with post-mortem human brain histology, choline acetyltransferase (ChAT) expressing neurons also degenerate
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744635/
So, the dopamine neurons drop causing the motion issues which cascades to a drop in acetylcholine, which is key to cognitive decline.
Dopamine and acetylcholine work hand in hand:
one being the motivation factor...a sense of action - the command; while acetylcholine does the heavy lifting...especially in the parts of the brain tied to think, planning, etc.
A quick look at supplementing choline (the precursor to acetylcholine):
CDP-choline may enhance dopaminergic therapy in Parkinson’s disease through multiple mechanisms, including decreased reuptake of dopamine leading to increased levels at the synaptic cleft. Additionally, CDP-choline activates tyrosine-hydroxylase and induces increased dopamine production.55
https://www.sciencedirect.com/topics/medicine-and-dentistry/citicoline
So...acetylcholine is critical to dopamine function including making more of it available and boosting production (but not in the tolerance-inducing way of L-Dopa).
Interestingly, guess where else those Lewy Bodies (concentrations of the α-synuclein protein tied to Parkinson's) show up?
LBs in remote locations, nonclassically linked to PD, such as the ENS, the olfactory bulbs and dorsal motor nuclei of the vagus nerve
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468760/
Ah-ha!
- Olfactory bulb - scent - hence the smell connection
- Vagus nerve - This hub of acetylcholine
It makes you wonder if the deficit in acetylcholine comes first since it's integral to producing dopamine!
As we mentioned, the Vagus nerve is a highway interchange between the brain and the gut.
Guess who's riding along?
"alpha-synuclein," a protein involved in a series of neurological disorders including Parkinson's disease, is capable of traveling from brain to stomach and that it does so following a specific pathway.
https://www.sciencedaily.com/releases/2017/01/170105123038.htm
More specifically:
The study also reveals a preferential route of alpha-synuclein transmission via the vagus nerve.
This is a great lead-in to our next section...gut inflammation and Parkinson's.
Gut inflammation and Parkinson's
We think they may have the direction backwards.
In our review of CBD and autoimmune, it's clear gut barrier breaks are key to bacteria gaining entrance to our body, to which, our immune system responds.
For example:
Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028032
Okay...that's interesting in itself...the gut barrier is not working. See CBD and leaky gut to learn more.
Then comes…
In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects.
Okay...E coli (remember the bacteria mix is different up top) and then...alpha-synuclein!
So...it's made its way to the gut (or maybe started there).
We would expect other risk clues.
Okay...like this one:
A Danish study of patients with inflammatory bowel disease (IBD) and Parkinson's disease (PD) found that patients with IBD had a 22% increased risk of developing PD over patients without IBD.
Check out CBD and IBD to learn more.
Does Parkinson's cause gut issues?
A growing body of research points to the role of the gut-brain axis in the development of PD, with inflammation, irritable bowel syndrome, leaky gut, and altered gut microbiota observed in the gut, often years before the onset of symptoms of PD.
No. The gut issues precede the onset of Parkinson's.
This is not surprising to us.
Everything we've looked at (anxiety, depression, autoimmune, etc) always shows inflammation in the gut.
The gut acts like an inflammation thermostat for the rest of the body...and the brain!
Interestingly, Devos et al. (2013) reported the inflammatory responses in the gut since the early stages of PD, by analyzing the ascending colonic biopsies of PD patients, they found that the pro-inflammatory cytokines (TNF-α, IF-γ, IL-6, and IL-1β) and glia markers GFAP and Sox-10 were significantly elevated, and some of them (IL-6, IL-1β, and Sox-10) were negatively correlated with disease duration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753187/
Let's translate. Basically, early with Parkinson's, there's an increased level of inflammatory agents.
These are important as we'll see what CBD does for these specifically.
Check out CBD and gut inflammation or CBD and microbiome to learn more.
What about the barrier with the brain?
The blood-brain barrier and Parkinson's
We have a secondary defense surrounding the brain as well.
Is there an issue there?
To the point:
In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD)
https://pubmed.ncbi.nlm.nih.gov/25757748/
Stay with us on this next piece because it ties it all together:
Here, we demonstrate that erythrocytes produce α-syn-rich EVs, which can cross the BBB, particularly under inflammatory conditions provoked by peripheral administration of lipopolysaccharide
https://pubmed.ncbi.nlm.nih.gov/28903781/
Let's translate, please.
Essentially...when bacteria is present (LPS), it causes inflammation along the blood-brain barrier, a boost of production in alpha-synuclein (the lead suspect with Parkinson's) occurs.
Goodness.
See why the gut barrier and brain barriers are so important!
When bacteria is able to jump across, bad things happen with our immune response (inflammation).
The mouth and nasal biomes are also in play.
Before we move on, let's look at just one example of a chemical that's eroding our gut barrier.
Glyphosate. Round-Up. Found in most corn, soy, and wheat in the US (outside of organic).
We've gone deeper into glyphosate at our CBD and leaky gut or CBD and gut inflammation but the tie-in with Parkinson's to bring this all together:
In multivariate analyses, both SNCA REP1 score and pesticide exposures were significantly associated with PD in younger subjects
https://pubmed.ncbi.nlm.nih.gov/18322262/
We won't bring up the 38-year-old subject who accidentally ingested glyphosate and got Parkinson's 4 years later.
https://pubmed.ncbi.nlm.nih.gov/30799335/
Our bad...Parkinsonism.
As we mentioned, there's a pipeline from the gut to the brain via the vagus nerve.
What about inflammation there?
Brain inflammation and Parkinson's
2019 research:
In Parkinson’s disease (PD), dopaminergic neuronal loss is accompanied by inflammatory changes in microglia, astrocytes, innate immune cells, and infiltrating peripheral immune cells.
https://link.springer.com/article/10.1007/s12272-019-01133-0
Microglia are the generals of our brain's inflammatory response.
Hyperactivation there is highly destructive if chronic as we've seen across mental health (see CBD and neuroinflammation or CBD and mental health).
Judging by the bacteria signatures weakening our blood-brain barrier from above, there's plenty to react to with Parkinson's.
In fact, one of the few bright spots for potential treatment is with neutrophils, which act like protective and rebuilding anti-inflammatory supports.
NFs are molecules produced mainly by neurons, which mediate synaptic plasticity, neuroprotection, neurorestoration and maintenance of neuronal functions.
https://www.frontiersin.org/articles/10.3389/fneur.2018.00860/full
So...we want to look at neuroprotective agents as well as those tied to repair replenishment in the brain.
What a great segue to CBD.
Research on CBD and Parkinsons
Thank you if you're still with us.
We've covered quite a bit but it's important to get all the NEW research which has changed so much literally in the last few years.
So...let's break down CBD research on Parkinson's along the following lines:
- CBD and neurotransmitters like dopamine and acetylcholine for Parkinson's
- CBD and gut barrier for Parkinson's
- CBD and brain blood barrier for Parkinson's
- CBD and gut inflammation for Parkinson's
- CBD and brain inflammation for Parkinson's
- CBD and BDNF (the star of THIS show!) for Parkinson's
- CBD and kinesia symptom
- CBD and Parkinson's research for Parkinson's
- Other tools for Parkinson's
Lots to cover but very exciting!
Let's get into it.
CBD and neurotransmitters like dopamine and acetylcholine for Parkinson's
We did deep dives on CBD and dopamine but our review of CBD and schizophrenia is more interesting.
Schizophrenia is characterized by too much dopamine in one brain area (the striatum) and a reduction in another area (prefrontal cortex).
The standard anti-psychotic basically hammers down dopamine which helps in one area (the "positive" symptoms like hallucinations, paranoia, etc) and not in the other (the "negative" symptoms like depression, withdrawal, etc).
The studies on CBD and schizophrenia or psychosis is something short of amazing in that it helped with BOTH sets without the nasty side-effect profile of amisulpride (tested anti-psychotic alongside CBD).
This means two different responses in two different brain areas depending on the state of that system!
Here's the key thing to know...
Serotonin is the master of dopamine...it controls its activity and levels.
CBD has a powerful effect on serotonin to "rescue" levels when low.
A study looked at depleted serotonin due to injury:
Overall, repeated treatment with low-dose CBD induces analgesia predominantly through TRPV1 activation, reduces anxiety through 5-HT1A receptor activation, and rescues impaired 5-HT neurotransmission under neuropathic pain conditions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/
So...CBD boosted serotonin (H5T) when low which lowered pain and anxiety.
The substantia nigra area which is specifically under siege with Parkinson's resides in an area called the striatum.
Look at CBD's effect there to protect neurons from assault in another debilitating neurodegenerative disease...Huntington's:
This indicates that CBD is neuroprotective but acted preferentially on striatal neurons that project to the substantia nigra.
https://pubmed.ncbi.nlm.nih.gov/17672854/
Goodness. That's right up our wheelhouse.
Remember, we don't see spiking of dopamine which would be bad and point to addiction.
CBD has been found to be non-habit forming and more importantly...it doesn't create tolerance.
Tolerance is a sure sign that a chemical is pushing a given pathway too much in one direction.
For example, L-Dopa builds tolerance. See CBD and tolerance to learn more.
What about acetylcholine and its main production hub, the vagus nerve?
CBD can support acetylcholine as shown in wake-promoting studies during day time:
Altogether, these data demonstrate that CBD increases ACh levels in a brain region related to wake control.
https://pubmed.ncbi.nlm.nih.gov/29876791/
Interestingly for Parkinson's, it also supports sleep duration and quality at night (see CBD and sleep).
And the vagus nerve...the inflammatory hub and transit between the brain and gut?
Together, these findings detail a novel excitatory action of CBD at vagal afferent neurons
https://journals.physiology.org/doi/abs/10.1152/jn.00128.2020?journalCode=jn
Remember that gut inflammation precedes Parkinson's and the vagus nerve may serve as the transit for the alpha-synuclein at the heart of the disease.
Speaking of gut inflammation…
CBD and gut barrier for Parkinson's
These days, all roads (research) lead to Rome (the gut).
Let's start with the barrier between our internal world and the very problematic external world (bacteria, viruses, mold, etc).
The gut barrier is so important to Parkinson's and autoimmune diseases.
What does CBD do there?
First, CBD has a potent antibacterial and antiviral effect.
Remember how E. coli was overabundant in the gut biome for people with Parkinson's?
CBD's effect:
We found that CBD is a strong inhibitor of MV release from Gram-negative bacteria (E. coli VCS257),
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747004/
MV is the way bacteria communicate with each other and interact with our cells.
The more interesting studies look at CBD's effect on gut barriers following the introduction to very nasty bacteria strains.
C diff is one of the worse (part of the hospital risk epidemic now).
It wrecks the gut environment and directly destroys our barrier there.
A Swedish study (very new) looked at connections with Parkinson's:
Across the entire follow‐up, a 16% elevation of PD risk was observed among the CDI group, which was mainly driven by increased PD risk within the first 24 months after CDI diagnosis.
Again, this points to the gut as being a key player with Parkinson's in general and C diff is just one version of nasty that can tip the apple cart.
CBD's effect after C diff exposure starting first with C diff's effect on the gut barrier:
Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721977/
Okay...to translate..C diff directly damaged a range of attributes for the cells that line our gut..especially the the proteins that build our barrier (occluden, occludin).
CBD's effect?
All these effects were significantly and concentration-dependently inhibited by cannabidiol
Check out CBD and gut barriers to learn more.
That's the finger in the dike...to prevent more damage.
We would expect effects on gut inflammation as well. Let's go there.
CBD and gut inflammation for Parkinson's
Damage to the gut barrier generally comes from an inflammatory state in the gut.
We've covered this in detail at our CBD and gut inflammation or CBD and IBD but some quick take-aways.
Scientist looked at the effect of CBD for mice exposed to bacteria and people with ulcerative colitis (a disease result from chronic gut inflammation).
CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/
Translation, please.
- CBD calms the immune hyperactivation (reactive gliosis)
- CBD calmed the inflammatory state in the gut
- CBD reduced damage to the gut barrier (remember, the two are tied)
- CBD did most of this via the PPAR pathway
We'll leave you with this fascinating study.
Essentially, researchers raised two sets of mice:
Mice with regular gut biome plus bacteria known to overproduce alpha-synuclein
Germ-free mice (not gut biome)
The former developed symptoms of Parkinsonism while the latter did not...until…
The gut bacteria from the former were transplanted to the latter!
They then took fecal samples for a person with Parkinson's and transplanted to the healthy mice.
Guess what happened?
The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces.
https://www.neurodegenerationresearch.eu/2017/03/parkinsons-disease-linked-to-gut-microbiome/
SCFA's are short-chained fatty acids, a by-product of bacteria breaking down fiber.
These can set off an inflammatory response in the immune system and some people (genetic or prior priming) respond too strongly.
Again...check out the gut inflammation article to really dive into this area.
Let's look at the next chink in the armor (to our brain).
CBD and brain blood barrier for Parkinson's
First, since CBD is fat-soluble, it's easily able to cross the blood-brain barrier.
A range of studies have looked at CBD's effect here across many issues.
Stroke is a big one.
A stroke causes a major assault to our blood brain barrier as collateral damage.
For example:
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://pubmed.ncbi.nlm.nih.gov/32183416/
Cytokines are the immune system's inflammatory assassins and ischemia is stroke.
Another study looked at oxygen deprivation (akin to stroke) and found the following:
These data suggest that preventing permeability changes at the BBB could represent an as yet unrecognized mechanism of CBD‐induced neuroprotection in ischaemic stroke, a mechanism mediated by activation of PPARγ and 5‐HT1A receptors.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761095/
PPAR is a fascinating anti-inflammatory pathway and 5HT is none other than...serotonin!
Check out CBD and endocannabinoid deficiency to learn more.
Let's turn to neuroinflammation..a hallmark of Parkinson's.
CBD and brain inflammation for Parkinson's
We have a giant review of CBD and neuroinflammation as it pertains to mental health.
Yes, the immune system is a big player there!
Maybe more so with neurodegenerative diseases like Parkinson's and Alzheimer's (see CBD and Alzheimers).
Let's go much deeper than 99% of the sites out there.
What actually is alpha-synuclein?
- First, it's abundant in the brain (strike 1).
- It's tied in with slowing down mitochondria function (we'll get to why below) - strike 2.
The newest research is eerily familiar from our deep dive on CBD and dementia.
We're talking 2020 research.
It's an immune responder! Initiator really.
Some clues first.
Recent studies have highlighted the invasion of circulating monocytes into the CNS in pathological conditions, where they make unique and important contributions to inflammation and neural injury
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405142/
Let's break this down because it brings everything you've read before together.
Basically, immune responders are leaking into the brain from the rest of the body.
That points to a damaged blood-brain barrier and this only happens when bad actors are crossing the blood-brain barrier (calling in the backup).
We have a whole immune response system specific to the brain with microglia being the generals.
You only need monocytes to enter when an alarm is sent out from the microglia. Send backup!
This speaks to two things:
- Blood-brain barrier issues
- Bacteria/virus circulating (which causes the inflammatory response).
Okay...so far...so good.
We see the hyperactivation of the brain's immune system in research:
The earliest evidence for the involvement of the immune system in PD pathogenesis came from the observation of activated microglia surrounding degenerating dopaminergic neurons in the SNpc of PD post-mortem brains
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405142/
There's the microglia. If they're activated, there's an infection generally. And look where it's happening...dopamine neurons in the substantia nigra!
The research gets technical but here's the key part…
Suggesting that α-syn may activate the innate immune system directly
To piece it all together:
- Bacteria/virus gains entry via gut barrier or mouth/nasal routes
- Bacteria/virus gain entry to the brain via the brain barrier or vagus nerve (from the gut)
- Brain immune response increases inflammatory response, one of those signals is alpha synuclein which is poorly structured and clumps up
Just like amyloid-beta (an immune responder) in Dementia!
It may be that alpha-synuclein is a byproduct of bacteria (remember the gut metabolite) which incorrectly signals to the brain that there's infection.
Clearly, brain inflammation is the net result as we iron out the mechanics.
CBD there from a Parkinson's review?
A laundry list:
The neuroprotective properties of CBD do not appear to depend on direct activation of CB1 receptors,94 but can be related to a reduction in glutamate excitotoxicity and oxidative stress,79 neuroinflammation decrease,91 anti-apoptotic action,92 or modulation/polarization of glial cells.93
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462020000200218
Let's break this down.
- Reduction in excess glutamate - too much glutamate is tied to Parkinson's symptoms
- Oxidative stress- from the mitochondria effects Reduction in neuroinflammation - the cytokines that reflect high inflammatory states
- Anti-apoptotic - prevents neuron death
- Glia cells - the microglia in control of hyperactive response in the brain!
We have major reviews on CBD and microglia, CBD and oxidative stress, CBD and glutamate.
Remember way back (a few thousand words ago) how a specific inflammatory agent called CCL2 may be attacking our dopamine-producing neurons?
Just as one example (albeit...very topical) from a study on MS:
CBD decreases VCAM-1, CCL2/CCL5 chemokines and TNFα/IL-1β.
https://www.sciencedirect.com/science/article/pii/S0969996113001939
Okay...that's the damaging side. What about the repair side?
Hello BDNF!
CBD and BDNF (the star of THIS show!) for Parkinson's
This is going to be your new best friend.
Every review we've done on any issue in the brain ends up here.
BDNF is the brain's fertilizer… the key to repair, replenishment, and growth.
It's the key to neurogenesis or the ability to make new brain and connections!
This is why exercise can be protective for Parkinson's.
It's the basis behind mindful meditation (see exercise and meditation for neurogenesis).
This is part of the new direction for Parkinson's research:
The body of data suggesting a relation between the decline of BDNF level and progression of PD is growing steadily
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037114/
Cut to the chase:
delivered BDNF is able to markedly rescue dopaminergic neurons in SN and dopaminergic projections to ST.
SN is the substantia nigra.
Okay...CBD's effect there?
Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex
https://pubmed.ncbi.nlm.nih.gov/29869197/
Okay, so a boost in BDNF signaling in the brain.
The prefrontal cortex goes through massive damage from Parkinson's and this is the basis for the cognitive decline:
Neuropsychological evidence reveals that Parkinson's patients are impaired on tests that are sensitive to prefrontal function (Zgaljardic et al., 2006), such as the Wisconsin-Card-Sorting Task (Gotham et al., 1988), attentional set-shifting (Cools et al., 2001), and spatial working memory (Lange et al., 1992).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836593/
Check out CBD and BDNF and CBD and brain repair to learn more.
What about the movement issue with Parkinson's?
CBD and dyskinesia symptom
There's research on CBD (and cannabis) for the movement symptoms of not only Parkinson's but L-Dopa treatment.
First, the L-Dopa effect.
Mice were given L-Dopa and the resulting movement symptoms appeared:
Unilateral striatal lesioned mice received L-DOPA for 21 days, developing severe axial, limb, locomotor and orofacial abnormal involuntary movements (AIMs).
https://www.sciencedirect.com/science/article/abs/pii/S096999611630153X?via%3Dihub
They found that CBD and capsaicin together reduced these movements:
CBD administered with the TRPV-1 antagonist capsazepine (CPZ) reduced AIMs.
Capsaicin is the pathway behind the hot feeling with chili peppers.
Interestingly, CBD also decreased the inflammatory markers that L-Dopa increases in the brain.
The studies show more effect for movement issues related to L-Dopa than for Parkinson's directly.
The capsaicin plus CBD however, has not been reviewed yet with standard movement issues and we look forward to further research.
We also need longer studies since BDNF takes a while to build and inflammatory states also require time to resolve.
Let's jump into actual research directly on Parkinson's and CBD.
CBD and Parkinson's research for Parkinson's
We need more studies and they're in the works.
Some current ones.
First, on the mental health aspects of Parkinson's (which are profound:
The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment.
https://pubmed.ncbi.nlm.nih.gov/18801821/
A study looked at CBD's effect on a broad-based scoring of Parkinson's effects:
However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05).
https://pubmed.ncbi.nlm.nih.gov/25237116/
Another study:
CBD was well tolerated, and all three studies reported significant therapeutic effects in non-motor symptoms (psychosis, rapid eye movement sleep behavior disorder, daily activities, and stigma).
https://pubmed.ncbi.nlm.nih.gov/30706171/
There's also research on Cannabis itself but we try to avoid that for this reason.
THC builds tolerance. This means that the pathways affected by THC will become less strong with time.
We cover this in CBD versus THC. There are other ways to get the benefits of THC (aside from CBD) which do not normalize or cause other issues which we'll look at next.
Other tools for Parkinson's
We looked at CBD above but there's other interesting research on the following:
- NAC - powerful antioxidant effects which act as a glutamate sink
- Vitamin D - master regulator of the immune system, gut health, and just about everything
- Berberine - powerful supporter of gut health and inflammatory state
- PEA - THC like effects without the high, tolerance, and cognitive issues
- Choline - the acetylcholine angle!
Let's touch on each of these for Parkinson's.
First, NAC.
NAC and Parkinson's
A study looked at dopamine function with NAC supplementation:
In the NAC group, significantly increased DAT binding was found in the caudate and putamen (mean increase from 3.4% to 8.3%) compared with controls (P < 0.05), along with significantly improved PD symptoms (P < 0.0001).
https://pubmed.ncbi.nlm.nih.gov/31206613/
DAT is the transporter of dopamine. We love NAC and there's a full review here.
It's safe, cheap, and directly supports anti-oxidation plus it's a huge protection against too much glutamate which we saw above for Parkinson's.
This is key to protecting neurons from damage!
Check out the review to learn much more.
Next up...everyone's favorite deficiency.
Vitamin D and Parkinson's
This deficiency gets worse as we get older (strike 1 for Parkinson's).
Vitamin D is key to explaining risk factors from living in higher latitudes:
Compared with controls, PD patients had lower serum vitamin D levels (WMD -3.96, 95%CI -5.00, -2.92), especially in higher latitude regions (WMD -4.20, 95%CI -5.66, -2.75).
https://pubmed.ncbi.nlm.nih.gov/30483205/
Strike 2.
Finally, Vitamin D is a powerful manager of the innate immune response (remember the alpha-synuclein piece).
To get technical…
Vitamin D analogs can decrease intracellular-free Ca (II) and downregulate the expression of calbindin-D28k to reduce α-synuclein aggregation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240665/
Vitamin D deficiency is tied to:
- Risk for Parkinson's
- Severity of Symptoms
- Rating on Parkinson's scoring test
Goodness. Let me guess...you're doctor hasn't requested a Vitamin D test?
Here's the interesting piece...the guidelines are at 30 which is for rickets and bendy knees.
Endocrinologists recommend 70-80! Check our full review on Vitamin D here.
Cut to the chase:
Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients
https://academic.oup.com/ajcn/article/97/5/1004/4577000?papetoc
The effects on Vitamin D and mental health are here.
Berberine and Parkinson's
We're just more and more impressed with research on berberine as it keeps coming in.
Granted, it's been used in Chinese medicine for centuries (goldenseal) but this is all about the gut.
Berberine is a powerful supporter of the gut barrier, gut inflammatory response, and microbiome.
From 2 days ago:
The findings, according to investigators, suggest that berberine might have positive effects on patients’ brain function by driving gut bacteria to produce l-dopa and increasing the levels of dopamine in the brain, via a vitamin-like effect.
https://parkinsonsnewstoday.com/2021/03/02/plant-compound-berberine-brain-function-parkinsons-study/
You have to understand that the bacteria mix in our gut directly controls neurotransmitter production.
Most of our serotonin (which drives dopamine) is made in the gut!
By bacteria!
Berberine is key to getting that house in order. Oregano oil is a powerful player for neutralizing bad strains but in a shorter duration.
We also like berberine for its longevity and metabolic effects (similar to metformin).
Our full review of berberine is here.
PEA and Parkinson's
Remember how we discussed a back-up option to THC?
Hello PEA (palmitoylethanolamide)
Don't let the long name scare you. Your cells are swimming in it right now.
Here's the hierarchy:
- Anandamide is our key endocanncannabinoid
- THC mimics anandamide but pushes too hard and for too long on the same CBD1 receptor (hence the downsides and tolerance)
- PEA supports anandamide function as a back-up
No high. No tolerance. No cognitive issues. Powerful anti-inflammatory responses and controls on glutamate.
As for Parkinson's??
Italian researchers found that when used along with standard medication, Normast (ultra-micronized palmitoylethanolamide, or um-PEA) helped lower both motor and non-motor symptoms in patients with advanced Parkinson’s disease (PD), and slowed disease progression and disability.
Also when used with L-Dopa to offset those negatives:
um-PEA add-on therapy to L-DOPA led a significant and progressive reduction of total score in Non-Motor Aspects of Experiences of Daily Living, decreasing from 9.7 ± 1.18 at baseline to 4.5 ± 0.69 at month 12.
https://www.eurekalert.org/pub_releases/2017-04/bsp-ucs041217.php
And for total scores:
Addition of um-PEA to PD patients receiving levodopa therapy elicited a significant and progressive reduction in the total MDS-UPDRS score (parts I, II, III and IV)
https://pubmed.ncbi.nlm.nih.gov/28325153/
PEA is safe, cheap, and readily available.
Finally, choline.
CDP-Choline and Parkinson's.
We touched on how acetylcholine is the new kid on the block for Parkinson's.
Remember, there's a powerful relationship between dopamine and acetylcholine.
CDP-choline (citicoline) is the best option.
Some examples from the research:
CDP-choline reportedly allows reductions in levodopa doses by up to 50% without any reduction in symptom control
https://www.sciencedirect.com/topics/medicine-and-dentistry/citicoline
This is critical since L-Dopa builds tolerance.
Furthermore..
CDP-choline may enhance dopaminergic therapy in Parkinson’s disease through multiple mechanisms, including decreased reuptake of dopamine leading to increased levels at the synaptic cleft.
In fact, even with the drop in L-dopa, the symptoms improved:
Citicoline was reported to effective in reducing levodopa by up to 50%, with improvement in the patient's rigidity, akinesia, tremor, handwriting and speech.
https://www.clinicaltherapeutics.com/article/S0149-2918(20)30518-X/abstract
Here's where it gets interesting…
Vitamin D may be involved in the regulation of acetylcholine and clearing of amyloid-beta, both of which are implicated in the pathogenesis of cognitive impairment in PD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267215/
This harkens back to research on sleep and sleep-movement issues where it was found that Vitamin D is essential for turning on specific acetylcholine neurons needed to stop body motion when sleeping.
Sleep is a known issue with Parkinson's and we may now know why!
We did a big review on acetylcholine.
Let's get to some practical questions.
How much CBD for Parkinson's
We can look at the research on neurogenesis for this.
Research has found that peak neurogenesis occurs around 300 mg/daily of CBD.
Afterwhich, it slows down as other pathways are triggered.
For that reason, this is our ideal target till we have more clinical trials.
Remember, neurogenesis and more specifically, BDNF, is a driving factor to replenishing and repairing the brain.
It turns out that this process is at the heart of how SSRIs work (until they don't due to tolerance) for depression.
See how SSRIs really work.
As for the other items:
- NAC - studies are generally around 1800-2000mg daily. It takes a few months to really get going
- Vitamin D - you need to test your levels. I take 10K daily and barely budge it (up to '50s now) since I have a VDR gene variant where I can't convert it well.
- Berberine - studies were around 500mg to 1000mg
- PEA - general recommendations are around 600mg twice daily
- CDP-Choline - Can go up to 2000mg daily (2 x 1000)
There's also some interesting research on B vitamins (B12 specifically) and how it's needed for acetylcholine processing.
Let's look at key questions on the type of CBD.
What's the best CBD for Parkinson's
There are basic requirements with any CBD:
- From Organically grown hemp in the USA at an FDA registered farm
- CO2 processed
- 3rd party tested
- No THC - THC builds tolerance which leaves us worse off than when we started
- No pesticides - obvious tied to Parkinson's
- No mold
- No bacteria
- No solvents
- No heavy metals
You can check our 3rd party testing here or at top of any page.
Then there's the question of CBD isolate versus full spectrum.
We have a whole review here but this is very important for Parkinson's.
It all comes down to histamine, the chemical behind allergic reactions.
There can be a very different response to CBD isolate versus CBD full spectrum depending on your histamine response.
Night and day side effect profile as you can see in our reviews.
If we've learned anything, it this:
Parkinson's is very much a disease of hyperactive or misaligned immune response!
Histamine is released from mast cells (see CBD and mast cells) and look at the curious connection with the immune assassin CCL2 we mentioned above:
Furthermore, mast cell-specific mediators were shown to trigger CCL2 and MMP-3 release by astrocytes and glia in this model system.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524694/
We don't want to trigger mast cell release of histamine as it's a weapon in our immune arsenal!
All the plant material in full-spectrum can elicit histamine response.
That's why we focus on CBD isolate and MCT oil from organic coconut oil.
Then there's cost!
At the 300 mg level for peak neurogenesis, we need to be able to afford this.
We price our 6000 mg bottle at 2-3 cents per mg of CBD before discounts up to 50%.
Our founder discovered CBD due to a brutal perimenopause (that story is here) and if we can help reduce suffering, so be it.
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.