Research on CBD and Mitochondria including Mitochondrial disease, Mental Health, and Aging

Research on CBD and Mitochondria including Mitochondrial disease, Mental Health, and Aging

CBD and Mitochondria disease

 

Our oldest members are finally getting credit.


The tiny little powerplants of our cells are turning out to be superstars of both health and disease.


Mitochondria are ancient bacteria that we either coerced or persuaded to power our bodies.


They even have their own DNA.


We're going to focus on what happens when they are not functioning correctly due to genetics, disease, injury, or age.


With NAD all the rage now, mitochondria require a deep dive as everything from mental health to cancer is in play.


We'll then turn our attention to CBD's effect on mitochondria for health.

 

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These are the topics we'll cover:

  • A quick intro to our cellular powerhouses
  • The curse that comes along with energy production - oxidative stress
  • Diseases tied to mitochondria function
  • Mitochondria and aging
  • How CBD affects mitochondria
  • What about THC and mitochondria?
  • CBD and mitochondrial disease
  • How much CBD for mitochondria support
  • What's the best CBD for mitochondria support


Let's get started!

A quick intro to our cellular powerhouses

The first introduction was about 1.5 billion (with a "b") years ago.


That's when our distant ancestor entered into an agreement with an ancient bacteria to share housing so to speak.


Mitochondria are essentially primitive bacteria that make energy for our cells to use.


Almost everything is powered by these powerhouses in our bodies and brains.


At its heart, the mitochondrial is an amazing little piece of biological machinery that combines electrical and chemical alchemy to turn simple sugars into raw energy to power everything in our cell.


Human cells usually have 1000-2000 mitochondria per cell with more energy-intensive cells demanding more.


Liver and heart cells are some of the most crowded!


The ties to aging are fascinating as we'll discuss below but remember that most disease is directly tied to aging which begs the question.


Is the mitochondria function tied to most diseases?


We'll look at that below.


Just look at exercise.


A recent study found that constant exercise can reduce the body's genetic and tissue age by 30 years at age 70.


This means that a person age 70 who exercised throughout middle age had the profile of a 40-year-old.


The association between exercise and longevity is curious since every time you exercise, a tremendous amount of inflammation is created.


Most of this is the result of energy created from the very same mitochondria needed to drive muscles.


Why would constant inflammation and pretty caustic waste material make your live longer and better??


Turns out that energy needs to drive mitochondrial production.


In fact, they can quickly grow in numbers if there's a need for energy.


This constant flux of numbers is very important since the endocannabinoid system (where CBD works) helps to govern cell birth/death as we'll find out below.


As with all energy production, there's always a downside.

The curse that comes along with energy production - oxidative stress

Waste product...the unwanted byproduct that comes with all energy production.


In terms of mitochondria, the waste material is in the form of oxygen.


The "oxidant" part of the antioxidant craze over the past few decades.


Oxygen is nature's little molecular scissors (which is why you find it cleaner).


It's incredibly destructive when roaming around neurons or even cellular machinery.


In fact, we have an entire system that's there to mop up excess oxidation which is carefully managed.


Glutathione is the heavy hitter (see CBD and glutathione) and we did a big review on NAC which supports this redox pathway.


Learn all about why oxidative stress is so important to mental health here.


When oxidative stress breaks out of control, actual cellular or DNA damage occurs and this can quickly spiral out of control.


That's one part of the equation but it deals mainly with activity from even healthy mitochondrial function.


What about when mitochondria are functioning correctly?

Diseases tied to mitochondria function

Simplicity is both an advantage and a potential weakness!


The DNA of mitochondria is completely separate from ours...its bacterial DNA in origin!


It's a very simple ring compared to our undulating spiral helix.


The issue is that mutations can (and do) occur which can quickly lead to problems in energy production.


Mitochondrial DNA or mtDNA does not have a great deal of "junk" or supportive coding which means a mutation is hitting something of importance when it does strike.


The mtDNA is also very close to the source of oxidative damage (the little oxygen scissors that can but DNA easily) which makes it more prone to damage.


Maybe most important, mtDNA doesn't have a powerful error correction system like our DNA.


Research is finally starting to understand the eventual repercussions of this process:

Mutations in mtDNA have been implicated in neuromuscular and neurodegenerative mitochondriopathies and complex diseases such as diabetes, cardiovascular diseases, gastrointestinal disorders, skin disorders, aging, and cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675848/


We get all our mitochondrial DNA from our mothers.


Since cellular metabolism (energy production and use) is tied to almost everything, let's focus down on mental health issues since we've covered it in detail at our CBD and mental health.


How would our energy production system come into play here?

Mitochondria and mental health

First, we love the fact that all the research on this front is in the last few years!


It shows just how new our understanding of this process is.


There's a known connection between mitochondrial disease and psychiatric illness:

In a review by Fattal et al. 2006 (10), the authors identified 19 confirmed case reports of mitochondrial disease with comorbid psychiatric problems, including MDD, psychosis, BPD, anxiety disorders, and personality change.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098560/


Here's the underlying process.


Stress, be it acute (think trauma) or chronic eats up our brain's energy balance. 


Something has to give and if mitochondria energy output is going to stress, basic housekeeping will suffer.


It's kind of like how your house becomes a mess during an emergency or flu.


What researcher is discovering is that under the "housekeeping" tasks is a list of very important interactions beside energy production:

Mitochondria play a role in amino acid, lipid, and steroid metabolism, apoptosis, and act as calcium buffers and sources of free radicals 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098560/


Goodness. 

  • Amino acids like tryptophan which is converted to serotonin (see CBD and serotonin)
  • Lipids - little tiny fats - the fuel of the brain and what endocannabinoids are made from
  • Steroids - powerful hormones with sway over neurotransmitters
  • Apoptosis - removal of cells which are broken or cancerous

Let's zero in on three high profile issues to see how this plays out:

  • Mitochondria and depression
  • Mitochondria and anxiety
  • Mitochondria and schizophrenia

First depression.


Mitochondria and depression


Check out our review on CBD and depression to get a lay of the land.


Depression is marked by brain loss in specific brain areas.


One suspect for this damage is oxidative stress and the connection with mitochondria:

Alterations in mitochondrial functions such as oxidative phosphorylation (OXPHOS) and membrane polarity, which increase oxidative stress and apoptosis, may precede the development of depressive symptoms.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997778/


Remember that apoptosis is the removal of cells or neurons.  Too much in this case as they're damaged from oxidative stress (see CBD and oxidative stress).


Why are SSRIs the go-to drug until they stop working due to tolerance or side effects?


Serotonin (the main target) boosts neurogenesis or the repair and growth of neurons!


Check out CBD versus SSRIs or How do SSRIs really work to learn more.


It's the other side of the coin….building a new brain to keep up with apoptosis.


Mitochondria are key to maintaining this balance as the load in the brain is ridiculous:

A resting cortical neuron consumes 4.7 billion ATP molecules every second 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997778/


ATP is the actual fuel product that mitochondria make.  That's one neuron at rest!


In fact, ATP is needed for signaling with serotonin  (the SSRIs) and norepinephrine (SNRIs)


There's quite a bit of research tying mitochondria DNA, function, and deficiency to depression and mood disorders.


The brain does not have the energy to keep up with the day to day toll.


It's even showing up in the mtDNA:

In one interesting study, long-PCR revealed that 68% of patients with depression have mtDNA deletions, compared to 36% of control subjects

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997778/


A study looked at the brains of people who had major depression and found 16 genes that were expressed differently than people without depression.  


Guess where they operated:

The identified genes are ones known to govern oxidative stress and neuronal ATP levels, suggesting for the first time that mitochondrial genes might be altered in tissue samples from human patients. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997778/


We'll look below at how to address oxidative stress.


Let's turn our attention to anxiety.

Mitochondria and anxiety

The connection is clear:

There is a bidirectional link between mitochondria and anxiety. Mitochondrial, energy metabolism, and oxidative stress alterations are observed in high anxiety; conversely, changes in mitochondrial function can lead to heightened anxiety.

https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(19)30123-7#


This keeps coming up and speaks to a deeper inability to manage the damage that accompanies energy production in the brain.


An interesting study looked at the effects of stress on mice.


They analyzed the differences between mice who responded with anxiety and those that did not.


One big difference lept out:

The analysis pointed to a number of changes in the mitochondria in the brain cells of mice exposed to frequent stress, compared to the non-stressed mice. 

https://www.sciencedaily.com/releases/2019/09/190926141747.htm


Needless to say, stress (be it physical or psychological) is directly tied to every mental health issues including anxiety.


The key there is:

cumulative effects of stressors eventually damage the mtDNA (e.g., mutations, deletions) and/or induce lasting changes in mitochondrial content and energy production capacity;

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901651/


Check out CBD and mechanisms of anxiety to learn more.


Let's turn to a developmental mental illness.

Mitochondria and schizophrenia

Speaking of an inflamed brain (see CBD and schizophrenia), newer research is pointing to the confluence of oxidative and inflammatory stress in the brain.


As for oxidative stress:

Mitochondrial deficit, altered redox balance and chronic low-grade inflammation are evident in schizophrenia. 

https://www.sciencedirect.com/science/article/abs/pii/S0149763414002887


Redox is the balancing act of oxidation in the brain.


This imbalance in oxidation can then lead to inflammation downstream:

It is hypothesized that oxidative/nitrosative stress responses due to mitochondrial dysfunctions might activate immuno-inflammatory pathways and subsequently lead to neuro progressive changes in schizophrenia.


The science quickly gets very complicated in how the mechanics of mitochondria affect the pathways of schizophrenia.


Let's dance around the edges.


Do we see higher oxidative stress with schizophrenia?


Taken all together, the majority of studies confirm that oxidative stress and oxidative damage is present in schizophrenia, in never-medicated and early stage of disease and in treated and chronic stage as well

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131721/


Our review of NAC really gets into this.


NAC directly supports glutathione, our primary protection from oxidative stress.


One example:

Participants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027).

https://www.cambridge.org/core/journals/psychological-medicine/article/cognitive-effects-of-adjunctive-nacetyl-cysteine-in-psychosis/5212DC4146E3D1B208CF8EE33426BE64


As for glutathione, another study looked at its level during the course of the disease:

All three metabolite concentration values in the ACC were significantly reduced in this group.

https://www.nature.com/articles/s41380-018-0104-7


The ACC is an important part of the brain and glutathione was out-gunned.


There's also a great deal of research on oxidative stress and autism.


Why do we focus on oxidative stress if our discussion is about mitochondria?


Thus, compromised mitochondrial function can result in impaired calcium buffering, apoptosis and over-production of reactive oxygen species (ROS)

https://www.nature.com/articles/s41598-018-24355-6


Check out CBD and schizophrenia.


Let's turn to aging.

Mitochondria and aging

Many diseases are directly tied to aging.


What about the process itself?


A recent study with mice show the power of mitochondria.


Mice were genetically modified to have reduced mitochondrial activity when given a specific antibiotic.


The target group started to age very quickly with all the telltale sizes for mice.


Wrinkles.  Hair loss.  Low energy.  Health issues.


They reversed the process and the aging effects reversed!


Aging is thought to only have one direction!


http://www.longlonglife.org/en/transhumanism-longevity/lifespan-news/mitochondria-reversing-aging-in-a-new-mouse-model/


This begs the question...is a slow reduction in mitochondria function (due to accumulating mutations) the root of aging?


There is an impressive review with links of mitochondria dysfunction to just about every key system in the body in terms of aging:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627182/


A key takeaway is that both COQ10 and VItamin D may offer benefits in supplementation for this pathway.


Vitamin D is so impressive that we did a full review here.


So...what do we do about all the malformed and malfunctioning mitochondria that build up and multiply (literally)?


Let's introduce you to a powerful pathway called AMPK.


This is an ancient pathway in our body to deal with bad times.


Famine.  Drought.  Lack of oxygen.  Basically, anything that threatens our existence.


It sends the body into a ramped-up efficiency in energy production and use.


That should cue some eyebrows since we're talking about mitochondria.


Here's the important piece:

Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780224/


Mitophagy.  That's the key piece!


It literally means the removal of faulty or bad mitochondria


The definition:

Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress.

https://en.wikipedia.org/wiki/Mitophagy.


AMPK is also tied to removing zombie cells (called senescent) that accumulate and leak out inflammation.


This is one of the big advances made in actually REVERSING aging.


Check out our review on metformin to learn more about this.  We also looked at fisetin to address another associated pathway for aging called mTOR.


This will all be watercooler talk in about five years.


The review of metformin looks at studies where aging was actually reversed in studies via this pathway.


Let's turn our attention to the endocannabinoid system...one last stop before CBD and other tools.

Endocannabinoid system and mitochondria

This is the system that CBD operates within.

 

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The ECS is generally tasked with balancing other key systems:

  • Nervous system - including neurotransmitters like GABA and serotonin from above
  • Immune system - inflammation and cellular growth/death balance
  • Endocrine system - hormones with powerful effects throughout the body and brain

First question...are there even endocannabinoid receptors on mitochondria?


Yes!


These lines of evidence highlight the direct association between mitochondrial CB1R and proper functioning of mitochondria, which has been suggested to participate in many pathological conditions

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/


Let's focus on the birth/death balancing act part.


Why?

  • Mental health - neurogenesis (birth side) is showing powerful effects across all mental health
  • Aging - removal of senescent or faulty cells is a critical pathway we can actually affect

Two specific examples from research focused on cellular balancing in the immune system and the brain.


The immune system because many auto-immune diseases are characterized by an overabundance of cellular activity in the immune system (psoriasis, etc).


The brain is obviously important for the other reason...cell death in key parts of the brain (dementia, Alzheimer's, Parkinson's, etc).


The endocannabinoid system was found to balance energy metabolism (translated as mitochondria) directly in the brain:

mtCB(1) receptors directly modulate neuronal energy metabolism, revealing a new mechanism of action of G protein-coupled receptor signaling in the brain.

https://www.ncbi.nlm.nih.gov/pubmed/22388959


"Mt" means mitochondria.  So...endocannabinoid receptors on the mitochondria regulates neuron energy function!


Let's look at an example that directly affects autoimmune, a disease that accompanies aging in most cases.


Part of the issue with autoimmune is excessive creating of inflammatory responders.  


Out of balance birth/death for immune cells essentially.


As for the endocannabinoid system?:

cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548/


Apoptosis means programmed cell death.


This is huge since most of our modern diseases are autoimmune by nature.


Check out CBD and autoimmune here.


Finally, let's really dig down deep.


Interestingly, cannabinoids are lipids...a discreet chunk of fat that's very useful to the body.


The membrane of the mitochondria is also lipid-based.


It was found that cannabinoids can absorb into the outer wall of the mitochondria and allow calcium to flow more easily.


Under periods of stress, calcium can build up and affect the mitochondrial's ability to remove waste and/or create energy.


Both bad things for our bodies!


CBD was directly implicated in helping this process so we'll save that for below.

http://www.jneurosci.org/content/29/7/2053


That's a great segue...let's turn to CBD finally.

How CBD affects mitochondria

Let's look at CBD's effect on three different aspects tied to the proper mitochondrial function:

  • Cellular repair, death, and growth
  • Removing waste products from mitochondrial "respiration"
  • Maintaining balance in mitochondria via calcium channels

First, the delicate balance of cellular birth and death


We know from autoimmune diseases that CBD directly affects the birth/death cycle when out of balance.


From our review of CBD and psoriasis:

Remember the apoptosis or removal of overabundant cells in the immune system (such as when they're attacking our own body!!)??


They demonstrated that CBD induced apoptosis in CD4+ and CD8+ T cell populations in a time- and dose-dependent manner. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548/


This is where CBD gets interesting…


It can have different responses depending on the state (and need) of the system!


Cancer is a perfect example of this.


Look at CBD's effect:

  • Healthy cells with low inflammation - CBD has no impact
  • Healthy cells with high inflammation - CBD reduces inflammation
  • Cancerous or virally infected cells - CBD INCREASES inflammation

Wait a minute...read that back over.  What's going on?


It all makes sense when you realize that the immune system's natural way to kill cancer cell (apoptosis) is by ramping up inflammation!


In this case, it's oxidative stress and that's clearly in the wheelhouse for mitochondria.


Radiation and chemo are essentially massive boosts in oxidative stress.


It's not just about removing faulty cells though.


CBD has a powerful effect on neurogenesis - building new brain cells!


Check out CBD and brain repair for more info.


This is incredibly important to mental health (see CBD and mental health) especially in certain key parts of the brain like the hippocampus (memory and mood control) or the prefrontal cortex.


One example:

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028668


This effect may be the most important effect of CBD in the brain.


It's not just the brain.


Bone?


The Journal of Bone and Mineral Research published a study showing that the cannabinoid cannabidiol (CBD) strengthens bones and accelerates the healing of fractures.

https://www.labroots.com/trending/cannabis-sciences/8584/cannabidiol-enhances-fracture-healing


Again, the ECS is everywhere in the body.


What about that powerful AMPK pathway for cellular housekeeping?


CBD increases phosphorylation of AMPK signaling proteins at early time points.

https://www.researchgate.net/figure/CBD-increases-phosphorylation-of-AMPK-signaling-proteins-at-early-time-points-A-B_fig2_341935024


What about all the destructive waste products from mitochondria?

Removing waste products from mitochondrial "respiration"

Remember the antioxidant craze from the '80s?


Vitamin C.  Vitamin E.  Just about every plant material under the sun?


Move over bacon:

CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C [4].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/


Glutathione is our primary defense against the product of mitochondria.


Remember, all that supercharged oxygen can cut and slice mitochondrial DNA as well and they're in the same neighborhood!


What about CBD and glutathione?

Repeated doses of CBD in inflammatory conditions were found to increase the activity of glutathione peroxidase and reductase, resulting in a decrease in malonaldehyde (MDA) levels, which were six times higher in untreated controls

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/


Six times reduction in key oxidation.


And again with skin cells inflamed in psoriasis:

Glutathione peroxidase activity (GSHPx) and glutathione level (GSH) were similarly changed after using CBD to treat UVB irradiated human keratinocytes.


But not so fast, it does the opposite in cancerous cells!:

The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. 

https://pubmed.ncbi.nlm.nih.gov/16909207/


In cancer cells, CBD reduced glutathione (essentially taking away it's protection) and boosted oxidation while not affecting neighboring healthy cells!


We're drifting into the realm of the immune system but it's fascinating!


Interestingly, CBD also affected upstream players in the entire antioxidant arsenal:

CBD also supports the action of antioxidant enzymes by preventing a reduction in the levels of microelements (e.g., Zn or Sn), which are usually lowered in pathological conditions. 


Zinc and selenium.  Again, the ECS (where CBD works) is a powerful balancing system with fingers in many pies.


Back to mitochondria.


Let's turn to how CBD directly affects the function of mitochondria.

Maintaining balance in mitochondria via calcium channels and other pathways

Let's really get into the nuts and bolts of CBD for mitochondria.


It's all about calcium.  Not the calcium in your bones.


In the body, calcium is a basic currency of cellular activity.


Every cell!  Like we said, very basic currency.


Think of all the different industries in the US.  Agriculture.  High Tech.  Energy, etc.


So different but they all use US dollars to operate.


Those industries could be heart, brain, and bone.  


Either way, calcium is a key player in how the different cells function.

 

It works like a valve at the cell wall to control activity along various pathways.  A cellular gas pedal if you will.


A study looked at how CBD had it's anti-cancer effects and found the following:

Instead, CBD directly targets mitochondria and alters their capacity to handle Ca2+

https://www.nature.com/articles/s41419-019-2024-0


Essentially, it opened the calcium floodgates to kill the cell.


That's with cancer.


What about with brain tissue after a stroke which shows a tremendous amount of damage to surrounding brain tissue?

 

CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers.

https://www.sciencedirect.com/science/article/pii/S221323171630338X


Basically, it managed the mitochondria function to avoid further damage.


Here's the key piece:

neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

Goodness.


  • Attenuate oxidative stress - it brought down the damaging effects of mitochondria
  • Enhancing bioenergetics - it made mitochondria balanced and efficient
  • Modulating glucose- remember that glucose is the fuel for mitochondria

Preserving energy and oxidation levels under severe duress!


We can drop the mic right now.


The biggest energy hogs (with most mitochondria) are the brain (we just covered) and the heart.


Look at CBD's effect there:

Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461586/


Dox is a chemotherapy agent that ravages heart function.


What about CBD's cousin, THC?


Different story.

What about THC and mitochondria?

The problem with THC is that it pushes in one direction.  Up up up on CB1 activity.


This is fine if you're low but not so as CB1 activity rises.


That's why THC builds tolerance and can have dose-dependent side effects.


How does this affect mitochondria?

Mitochondrial coupling (V max/V 0) was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P < 0.001). 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310259/


Mitochondrial coupling is the machinery of how actual particles of energy move in the mitochondria.


THC reduces this.


This study was in the brain!


What about oxidative stress?


Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P < 0.05) and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P < 0.001).


H2O2 is a supercharged particle of oxidative stress.  Plus, more of it escaped.


In fact, CBD has gained recognition for its ability to offset the effects of THC, and mitochondria function appears to be no different in this regard.


The bigger issue is this...THC interrupts proper energy production:

Comparison with a variety of mitochondrial inhibitors demonstrates that THC produced effects similar to that of carbonyl cyanidep-trifluoromethoxyphenylhydrazone, suggesting uncoupling of electron transport. 

https://journals.physiology.org/doi/full/10.1152/ajplung.00157.2002


It literally bogs down the process of energy production in the mitochondria.


Check out why CBD is a must if you use cannabis.


Let's turn to CBD for serious consequences of mitochondrial function.

CBD and mitochondrial disease

The crux of mitochondrial disease is a reduction in energy production and other housekeeping effects.


This is usually due to a genetic mutation that can be passed down from the mother (since mitochondria come from our mother).


Mitochondria energy production is fascinating...like a chemical assembly line with stages of energy output.


There are 4 main 'complexes" or divisions of the chemical process...each squeezing more energy out of the available fuel and chemical soup.


Here's the important piece for CBD and mitochondrial disease:

Chronic and acute CBD administration increases the activity of mitochondrial complexes (I, II, II-III, and IV), 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958190/


There are many pathways that feed into the energy production chain.

  • Calcium
  • ROS (oxidative stress)
  • Inflammation

Let's look at these pieces.


We already say how CBD would control calcium channels to initiate cell death in cancer.


What about when the cell just needs a boost?


under pathological conditions involving mitochondrial dysfunction and Ca2+ dysregulation, CBD may prove beneficial in preventing apoptotic signaling via a restoration of Ca2+ homeostasis.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666323/


Homeostasis is a fancy word for "balance".  In this case, CBD did the opposite of what it does with cancer...it prevented the cell death process.


We saw with faulty cells how CBD would increase oxidative stress to kill them off...what about the opposite?


A study looked at oxidative stress and the damage this caused to the heart from diabetes.


CBD's effect:

Remarkably, CBD attenuated myocardial dysfunction, cardiac fibrosis, oxidative/nitrosative stress, inflammation, cell death, and interrelated signaling pathways

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026637/


We saw above how CBD had the same effect following stroke (see CBD and brain damage or CBD and TBI for more info).


What about the inflammatory pathways?


Why is this important?


Just this:

Mitochondrial dysfunction increases pro-inflammatory cytokine production and impairs repair and corticosteroid responsiveness in lung epithelium

https://www.nature.com/articles/s41598-019-51517-x


When mitochondria are not functioning, it leads to spiral of inflammation.  Cellular inflammation.


CBD's effect there?


BD treatment decreases the levels of the pro-inflammatory cytokines IL-1β, TNF-α, IFN-β, IFN-γ, IL-17, and IL-6 and increases the levels of the anti-inflammatory cytokines IL-4 and IL-10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958190/


That review goes into a litany of inflammatory agents that are positively affected by CBD.


We don't have trials yet for CBD and mitochondrial disease (unfortunately since there's not much available on that front).


The underlying research though is very promising.


Let's look at other tools to support mitochondrial function.

Other tools to support mitochondrial function

CBD is quite impressive but other tools can work alongside it.


Here are key players to look at:

  • Exercise - directly boosts mitochondria numbers and function
  • NAC - supports our redox or oxidative stress response (see review here)
  • Vitamin D - get your numbers tested and aim for 70-80 nmol/l (30 ng/ml) - we're not trying to avoid rickets and bendy knees any longer!
  • COQ10 - directly involved in the process (why it's so important for the heart which is energy-hungry)
  • NAD - a raw material for the energy process - key for people with low mitochondrial function
  • L-carnitine - interesting research on how it supports mitochondrial function

Let's look at practical questions regarding CBD. 

How much CBD for mitochondrial support

We don't have hard research on this front but we can look to interesting studies on neurogenesis.


Studies show that neurogenesis (building new brain tissue) peaks at 300 mg/daily for CBD.


More acute issues go up to 600-800 mg of CBD with strong safety profiles (schizophrenia, social anxiety public speaking, withdrawals, etc).


That's probably the high range and we looked at CBD use the long term here.


Since mitochondria function directly ties into the balance of cell birth/death, our best bet is on the neurogenesis effect at 300 mg/daily.

What's the best CBD for mitochondria support

There are basic requirements for CBD (which are not generally met on the market):

  • Organically grown in the US at FDA registered farms
  • CO2 processed
  • 3rd Party Tested
  • No THC - THC pushes in one direction be it immune suppression or otherwise.  
  • No Pesticides
  • No Heavy metals
  • No Solvents
  • No Bacteria
  • No Mold

We test ours twice since our whole family uses it!


Then, there's the question of full-spectrum versus CBD isolate.


Here's the issue…


40-60% of the population has histamine (allergy) issues and this goes up for women and as we get older (thanks for leaving, progesterone!)


There can be a very different side effect profile between full-spectrum and CBD isolate.


All the research is tied to CBD isolate...not full spectrum.


We did a complete review of CBD isolate versus full spectrum.


Then there's the question of cost.


The key metric is the cost per mg of CBD and we price our 6000 mg bottles (about 200 mg per dropper) at 2-3 cents per mg before discounts up to 30%.


If you read our story here, we found CBD from suffering and so we want to help people avoid the same.


Be well.  Take care of each other.  Take care of yourself.

 

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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.

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