We just wrapped a big review of CBD and TBI.
Interestingly, a question comes up in terms of whether CBD causes damage itself!
There's some confusion with its cousin THC on this matter so let's jump into it.
We'll dive into CBD and brain across the research.
Some damage is slow-rolling such as with oxidative stress, medications or exaggerated immune response.
Other damage is more pronounced such as TBI or from drugs.
We'll look at all of this and also address the question of CBD's effect on the brain itself.
This is very important because it speaks to the way CBD works in the body which is quite different from other substances.
Here are the categories we'll cover:
- How does CBD work in the brain
- Can CBD cause brain damage
- Can CBD help with brain damage
- CBD and TBI
- CBD and stroke
- CBD and THC
- CBD and the prefrontal cortex
- CBD and hippocampus
- CBD and neurotransmitters
- CBD and white matter superhighway
- CBD and neuroinflammation in the brain
- CBD and oxidative stress in the brain
- CBD and immune response in the brain
- CBD and neurogenesis (brain repair)
- What's the best dosage for CBD and brain damage repair
- What's the best type of CBD for brain damage repair
We have lots of research across these different topics so we'll give overviews and point out to that research.
Let's get started. This is your brain on CBD.
How does CBD work in the brain?
First, a quick lay of the land.
We'll look at brain function through different lenses:
- Brain areas and physical connections
- Brain immune response system (more than meets the eye)
It's amazing that it works at all.
The complexity of both the physical and chemical workings of the brain is phenomenal and we don't even fully understand it!
Some systems are become more "known" than others.
For example, there's a tug-of-war of sorts between the newer addictions (evolutionarily and developmentally speaking) such as the cortex and the more "reptilian" areas of the brain which we share with most animals!
This battle for control can cause issues if going the wrong way.
For example, if our prefrontal cortex (logical gate) isn't able to keep the amygdala (fear, emotion, etc.) center restrained, anxiety, OCD, depression, or other issues can occur.
Then there's the messengers of brain activity itself...the neurotransmitters.
- Serotonin - manages all human behavior and more
- Dopamine - key to rewards circuit - the reason you get anything done (or just use cocaine instead) and it's downstream metabolites norepinephrine and adrenaline!
- Acetylcholine - learning, focus, and brain plasticity (ability to change)
- Glutamate- the "gas" pedal of the brain but keep it under control!
- GABA - the "brake" pedal of the brain - keep glutamate in check and calm things down
Heavy hitters with a slew of minor players below.
Finally, there's the immune system.
We think of infection for the immune response but that's just the tip of the iceberg..Especially in the brain.
The immune system is tasked with balancing the growth and death of neurons in the brain.
Literally, the architect of brain connections!
Much of the "damage" that occurs in the brain comes from the following:
- Overactive immune response
- Oxidative stress
- Inability to repair
So...how does CBD figure into this equation?
CBD interacts with our naturally occurring endocannabinoid system.
This system is tasked with balancing key systems:
- Nervous system - neurotransmitters
- Endocrine system - hormones
- Immune system - inflammation and cell birth/death balance
Goodness...we just listed two of three we mentioned and hormones are critical to the interactions of the two.
Especially, our steroidal hormones. Estrogen drives serotonin. Progesterone drives GABA (and controls immune response). Testosterone drives growth factors!
Here's the key with CBD and the only reason we write about and research it.
CBD doesn't just push in one direction!
It works like a feedback mechanism in key systems.
This is important since pushing in one direction eventually causes damage or even tolerance.
That's the issue we have with THC (why CBD is a must if you use cannabis).
Technically, CBD is caused an allosteric negative modulator but that's short for feedback.
Due to this, we see interesting results in every pathway we study.
For example with cancer (touches on cell death):
- Healthy neuron with low inflammation - CBD has no effect
- Healthy neuron with high inflammation - CBD reduces inflammation
- Cancerous or virally infected cell - CBD INCREASES inflammation
Read that back over. Three different results from three different situations.
This is a great tie in with brain damage since inflammation and oxidative stress (especially) are huge players in what damages the brain.
We'll look at those below but the key takeaway is this:
There's a delicate balance act between insults to the brain (inflammation, oxidative stress, immune response, trauma, stress, etc.) and the repair process (serotonin, BDNF, neurogenesis).
When our brain loses this battle either abruptly (injury, drugs, etc.) or over time (stress, immune response, etc.), damage occurs.
Let's turn to questions specifically on CBD and brain damage.
Can CBD cause brain damage?
This question comes up.
Let's look at what research says.
There is no research showing damage to the brain from CBD use either acutely or long term.
In fact, the bulk of research is on how CBD helps following injury or brain damage.
So why does the question come up?
Guilt by association.
Many people new to CBD automatically associate it with THC, its cousin in the cannabis plant.
CBD is completely different from THC...even polar opposites in many pathways.
As for brain function, here are key differences:
- CBD does not impair motor function and cognition like THC
- CBD does not reduce grey matter superhighway like THC
- CBD does not affect memory like THC
- CBD is not psychoactive (technically...psychomimetic) like THC
In fact, CBD is used to counter many of these effects of THC in the body. Again, polar opposites.
As researchers put it for THC users:
Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory.
As to our point though:
No impairments to cognition were found, nor were there deleterious effects on psychological function.
Cognition is thinking. No negative effects to psychological function (in fact, the opposite with improvements on anxiety and depression).
The better review is CBD versus THC to understand why this question even comes up.
Many studies look at CBD's effect on brain function following various insults such as chemicals, inflammation, oxidative stress, and the like.
Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol.
The bigger question for us is normalization.
CBD does not build tolerance long term which is probably it's most important factor.
Let's turn to more research on the brain damage side.
Can CBD help with brain damage?
We'll look at specific situations below but let's first drill down to the key components we talked about above:
- Hyperactive immune response
- Brain area connectivity and volume
- Neurotransmitter balance
- Stress and oxidation response
First, the immune response which is a common culprit in brain damage.
In all these situations, CBD has positive effects in the brain.
We'll get into specific research on each below.
This isn't magic (although it seems to good to be true) but a function of the underlying endocannabinoid system that it works in.
Where THC pushes in one direction (increase CB1 activity like anandamide), CBD has differing effects depending on the state of the system.
This is so important with the brain since there are delicate balancing systems that are complicated and interconnected.
We'll look at them below in the neurotransmitter system.
Let's layout the usual suspects for causing brain damage so we'll be ready for the sections below:
- Overactive immune response - collateral damage of our immune response in the brain is bad news
- Oxidative stress - the energy-hungry organ in the body (aside from maybe the heart) creates lots of waste material
- Inflammation - really a part of the immune system but equally destructive
- Neurotransmitter imbalances - glutamate figures strongly here on the damaging side, serotonin on the repair side
- Leaky brain blood barrier - bacteria can come in which leads to damaging immune response - the gut is key there!
- Chemicals and drugs - upsets the delicate balance of the brain or ramps up pathways too strongly
- Trauma and chronic stress - fast or slow-motion damage from stress hormones and impaired repair
- Genetics - certain pathways don't function at full speed
Okay...let's dig deeper. We'll start with various injuries first since they are obvious.
CBD and TBI
As we mentioned, we did a deep dive on CBD and TBI which lead us to brain damage.
Dozens of NIH studies reviewed there but we'll focus on some endpoints.
Most of the research is still at animal level with CBD and TBI specifically which is a shame considering the lack of options for people following TBI.
CBD given to one group of the rats had the following effect:
Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury
Those are all measures of motor skills.
Another study looked at the many resulting symptoms of TBI on mice and found the following:
CBD oral treatment restored the behavioral alterations and partially normalized the cortical biochemical changes.
This is really important since we both affect (behavioral improvement) and cause (normalized brain chemistry).
That last review summarized with the following:
our data show some of the brain modifications probably responsible for the behavioral phenotype associated with TBI and suggest the CBD as a pharmacological tool to improve neurological dysfunctions caused by the trauma.
Again, we go into all the aspects affected by CBD for TBI at that review.
Serotonin. Inflammation. The works!
Let's turn to another common source of brain damage.
CBD and stroke
Stoke is another source of brain damage with the same inflammatory response combined with loss of blood flow and oxygen to key areas of the brain.
What does research show for CBD and stroke?
First, animal studies...bare with us...we'll translate the gobbly-gook:
CBD reduced acute (LDH efflux to the incubation medium) and apoptotic (caspase-9 concentration in tissue) HI brain damage by reducing glutamate and IL-6 concentration, and TNFalpha, COX-2, and iNOS expression.
Buried in that Klingon is some fascinating information.
Essentially, stroke was induced in mice.
CBD lowered both the immediate brain damage and the longer-term resulting brain damage from inflammation.
Glutamate is our gas pedal and when it runs too hot, neurons literally die from excitotoxicity.
Then there's the follow-up inflammatory agents which cause long-term damage as the immune system is stuck in a heightened mode.
CBD also calmed this response but more importantly...reduced brain damage that results from these pieces!
Another study severed a main artery in the brain of rats and looked at CBD's effect:
Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation.
Okay...so loss of brain material (neurons). Apoptosis is a fancy way to say cell death.
The last two pieces are very important. The microglia are the managers of our immune response.
A big piece of brain damage that results occurs from friendly fire after the injury. The immune system isn't able to "stand down".
Check out CBD and microglia to learn more as this figures into many mental illnesses.
CBD calmed that response.
We look forward to further trails for CBD and stroke in humans.
Let's turn to THC.
CBD and THC for brain damage
We already addressed the curious relationship between CBD and THC.
This first caught our attention with studies showing how THC causes damage to connective tracts in the brain between different brain areas.
These white matter highways are extremely important for a functioning brain.
First...the bad news:
Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus.
This was due to THC's effect as CBD has a very different profile:
It is important to note that the two major components of marijuana, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have opposite effects behaviorally, symptomatically, and in terms of functional activation of all of the regions-of-interest for the current study.
The hippocampus is so important and we'll look at it specifically below.
Look at what CBD does in terms of the damage caused to the hippocampusfrom THC:
Associations between greater right subicular complex and total hippocampal volume and higher plasma CBD concentration were evident, particularly in heavy users.
The more the CBD in the cannabis (as a ratio to THC), the more the hippocampus was protected.
We look at this pathway and more at our Why CBD is a Must if you use Cannabis review.
Also, check out whether people are chronically using cannabis to calm down glutamate. It's a fascinating look at why roughly 9% of cannabis users become addicted.
Let's zero in on brain areas associated with damage. We'll stay with the highlights.
CBD and the prefrontal cortex brain damage
It's what makes us human. Or primate, anyway.
The prefrontal cortex is the newest addition to the party in terms of brain function and evolution.
It operates as the seat of planning, thinking, reflection, and logic.
The prefrontal cortex also has the heady job of keeping our more primitive brain areas and their constituents in check (fear, anger, impulse, etc.). Brain damage here is especially debilitating.
What about CBD's role there?
- An interesting study comes up with CBD and depression for this brain area.
- Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex
Goodness. Let's break that down because it's too fascinating.
Depression can result from a loss of connectivity (slow-motion brain damage) in the prefrontal cortex.
This could be the result of genetics, stress, trauma, neurotransmitter imbalance, inflammation,etc.
The really fascinating part is how it does this.
CBD directly boosts BDNF (our brain's fertilizer...we'll discuss later) and new brain connections (synaptogenesis).
Stress is a villain for prefrontal cortex function and recovery from damage.
A study drilled down to see that DNA activity was actually reduced as a result in this brain area and look at CBD's effect:
Also, stress-reduced DNA methylation and DNMT activity in the HPC and increased it in the PFC. CBD and DNMTi treatment prevented these changes in both brain structures.
So...essentially stress turns off DNA activity (metalization) in the prefrontal cortex and CBD prevented this!
A very recent study looked at scans of blood flow and found the following:
In the prefrontal cortex, the area of the brain used for planning and decision making, CBD caused a significant increase in blood flow in the orbitofrontal cortex.
Let's turn our attention to the most vulnerable area of the brain (behind the prefrontal cortex).
CBD and hippocampus damage
The hippocampus may be the most dynamic area of the brain.
It has to be since it's the seat of memory.
Constantly writing, re-writing, and even erasing.
With that ability to change comes risk!
Combine this with a powerful management role for mood and we have a very important piece of real estate deep in the more ancient part of the brain.
Damage to the hippocampus is tied to every mental health issue and all insults above can leave their mark on its function and even volume.
We're more focused on the mood control element than memory but both are affected by CBD.
Look at CBD and hippocampus neurogenesis:
Overall, available data supports that CBD-induced adult neurogenesis can account for the protective effects of CBD in certain psychiatric conditions
There's a massive review of all the various pathways including the hippocampus.
CBD did not impair learning but increased adult neurogenesis
A more recent study looked at blood flow (a determining factor for brain activity) and found the following:
CBD significantly increased blood flow in the hippocampus
Check our CBD and hippocampus neurogenesis for anxiety.
This area is so critical to mood and mental health!
We also looked at exercise and mindful meditation for hippocampus neurogenesis.
Let's turn to the currency of the brain for damage and repair.
CBD and neurotransmitters for brain damage
We're going to focus on just two for now...glutamate and serotonin.
Glutamate is key to brain growth and activity but too much is very destructive.
Serotonin is key to stress response (a major source of damage) and the repair process.
In fact, serotonin drives BDNF, our brain's fertilizer which is going to be THE hot topic for the 2020s.
We'll get into it below but let's focus on glutamate and serotonin.
First, glutamate and brain damage/repair.
Glutamate is like gasoline. Controlled, it drives the engine of the nervous system.
Too much, too fast and it explodes.
CBD affects this pathway by supporting the "brake" pedal, GABA.
GABA opposes glutamate in a carefully managed balance.
CBD is a feedback mechanism for GABA function.
This is a big part of its effect for anxiety, OCD, and sleep.
An interesting study looked at CBD's effect on GABA and glutamate balancing between controls and people with autism (where glutamate can be imbalanced):
Thus, CBD modulates glutamate-GABA systems, but prefrontal-GABA systems respond differently in ASD.
Specifically, CBD increased the GABA function but in away that doesn't normalize (like benzos - see CBD versus benzos).
Balance is key there since glutamate is needed for sufficient activity but too much is destructive.
Also, check out the following:
- NAC - acts as a glutamate sink when excessive
- Magnesium glycinate - blocks glutamate activity naturally
Let's turn to that white matter area.
CBD and white matter superhighway
We already looked at how CBD protected our white matter that acts as a communication hub from the effects of THC.
An interesting study looked at the effects of CBD on white matter following stroke (a main driver of brain damage):
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.
- Hippocampus. Check.
- White matter. Check
- Immune response (glial). Check
This is exciting news.
The study also looked at neurogenesis which we'll get into below. That's the key to recovery following brain damage.
Let's turn to inflammation in the brain first.
CBD and neuroinflammation in the brain
As we mentioned above, inflammation and the immune response is key to the initial injury but can actually do more harm than good if not resolved.
We did a full review on CBD and neuroinflammation but some key takeaways.
There are many studies looking at CBD's anti-inflammatory effects.
We can zero in ones that deal with damage from injury or infection.
CBD diminishes inflammation in acute models of injury and in a viral model of MS through adenosine A2 receptors
MS (see CBD and autoimmune) caused by a virus is a known source of severe damage in the brain and nervous system.
Then there's CBD's effect on anandamide, our naturally occurring brain protector.
The net result of boosting anandamide (by blocking it's breakdown actually) can be found here following injury:
Animal studies indicate that post head injury administration of exogenous CBD reduces short-term brain damage by improving brain metabolic activity, reducing cerebral hemodynamic impairment, and decreasing brain edema and seizures.
Again, check out the neuroinflammation and CBD review here.
Let's turn to a different type of inflammation.
CBD and oxidative stress in the brain
A big source of damage in the brain following injury or just from daily workings of the brain is oxidative stress.
These "free radicals" are a result of how our cells make injury and the most energy thirsty organ in the body is the brain!
It generates lots of "waste" material in various forms of oxygen...nature's little scissors.
The ability to "mop" up these particles is critical to preventing damage.
CBD has shown powerful effects there.
A study looked at oxidative stress following infection in the brain:
The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD.
CBD is even better than Vitamin C and E, two powerhouses of the antioxidant system:
CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C .
Let's turn to the overarching immune setting in the brain as it pertains to damage.
CBD and immune response for brain damage
As we mentioned, the microglia are the generals of our brain's immune response.
When they're hyperactivated or activated for too long, damage can occur. No...WILL occur.
This research says it perfectly:
Microglial cells play a significant role in maintaining brain homeostasis and surveillance.
Homeostasis is a fancy word for "balance".
This is very relevant to dementia or Alzheimer's (see CBD and dementia) which is turning out to be a disease of the immune system.
As for CBD:
In summary, CBD is able to modulate microglial cell function in vitro and induce beneficial effects in an in vivo model of AD
Microglia are the key to our brain's immune response but it's not just responding to damage.
Microglia are the architects and involved with removing damaged tissue or coordinating new connections and growth...key to repair.
We're almost to that area.
Check out CBD and microglia to learn more.
Next stop, the blood-brain barrier.
CBD and blood-brain barrier
One of the first injuries following brain damage is to the blood-brain barrier.
This is critical since it protects our brain from chemicals and pathogens (bacteria, etc.) that get into our bodies.
An original injury or chronic small slights damage the BBB and look as the net effect of this:
Once this barrier is disrupted, secondary changes such as edema, inflammation, and hyperexcitability often occur.
Inflammation...what we're trying to reduce.
Hyperexcitability?? That's excess glutamate! The one thing we're trying to keep in check since it's so destructive.
We did a full review of CBD and the blood-brain barrier (so important for autoimmune and mental health) but some quick takeaways.
A study summarizes the effect of CBD following stroke (ischemia):
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.
Another study looked at CBD before and after brain damage was caused by oxygen deprivation to neurons:
CBD (10 μM) prevented the increase in permeability caused by 4 h OGD. CBD was most effective when administered before the OGD, but protective effects were observed up to 2 h into reperfusion.
So...even after the injury, CBD was able to offset the blood-brain barrier damage.
The net effect of this?
CBD also reduced cell damage, as measured by LDH release and by markers of cellular adhesion, such as the adhesion molecule VCAM‐1.
Let's finally turn to the most important part of this entire article.
CBD and neurogenesis (brain repair)
Mitigating current and further damage is what's we've discussed above (anti-inflammatory, anti-oxidative stress, blood-brain barrier protection, etc).
What about existing brain damage?
Let's now finally introduce neurogenesis, the process of building new brain material and connections.
Without neurogenesis, the brain is in stasis...actually deteriorating second by second under the weight of small damage incurred.
Death by a 1000 cuts.
This is the "homeostasis" mentioned above. Balance between cell destruction and cell creation.
Following any type of brain damage, this system is critical to change and recovery.
Serotonin is a master regulator here and this is why SSRIs even work at all (till they stop due to tolerance).
The real star though is BDNF, brain-derived neurotrophic factor.
It's the brain's fertilizer and research is finally understanding how it's the key to so much of what happens in the brain.
IT's everywhere in the research. The newer research, that is.
One of the two main reasons for drug relapse? Reduce BDNF levels.
Let's look at BDNF and brain damage before looking at CBD's effect there.
Researchers genetically engineered mice to make less BDNF and then cut arteries in the brain.
The results were striking:
Mice lacking both alleles for neurotrophin-4 (nt4-1 -) or deficient in a single allele for brain-derived neurotrophic factor (bdnJ+/-) exhibited larger cerebral infarcts compared to wildtype inbred 129/SVjae mice (68% and 91 %, respectively, compared to controls).
The mice with reduced BDNF had much larger areas of damage following the same injury!
Another study looked at "recovery" of function after injury with BDNF and omega 3's:
Dietary Omega-3 Fatty Acids Normalize BDNF Levels, Reduce Oxidative Damage, and Counteract Learning Disability after Traumatic Brain Injury in Rats
Omega 3's (fish oil, etc.) have been known for some time to help with brain damage and trauma.
It turns out the BDNF rescue is a big part of their effect.
BDNF is also what's behind psilocybin, ketamine, and even….CBD.
Remember the study on CBD's antidepressant effects due to serotonin and "plasticity" in the brain?
Again, the star player there:
The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus (HPC).
Our two favorite brain areas...the prefrontal cortex and the hippocampus.
Most interestingly, when they block the mechanism that produces BDNF, the positive effects on depression and mood went away.
BDNF folks...it's your new best friend.
Exercise and mindful meditation both exert their positive effects via BDNF as well (along with other pathways of course).
Let's turn to practical questions.
What's the best dosage for CBD and brain damage repair
We actually have some good research here especially on the neurogenesis front.
Research shows that it operates on a bell curve in terms of brain repair.
300 mg/daily appears to be peak neurogenesis in terms of CBD isolate.
Generally, there may be a higher dosage reflected in the research initially (withdrawals - 2-10 days) or acute mental health issues (psychosis - panic attacks, etc) of 600-800 mg daily.
The longer-term peak then appears to be 300 mg/daily for maximum neurogenesis which is the key to rewiring and "restocking" the brain following damage.
But what kind of CBD?
What's the best type of CBD for brain damage repair
First, there are basic requirements that are a must:
- Organically grown industrial hemp in the USA at FDA-registered farms
- CO2 processed
- 3rd party tested (essential)
- No THC - we already noted how THC has its issues in the brain for damage
- No Pesticides
- No Heavy Metals
- No Solvents
- No Bacteria
- No Mold
Those are critical and we actually test our oils twice - the whole family uses them.
Then there's the question of full-spectrum versus CBD isolate (CBD by itself).
We did a whole review on that here but all the research mentioned above and throughout the site is for CBD isolate.
There isn't good research on full-spectrum and more importantly, 40-60% of the population has histamine issues.
This number goes up as we get older and for women (thanks for leaving, progesterone!)
We consistently see where people have bad reactions or side effects to full-spectrum which goes away with CBD isolate.
That's originally how we found isolate...after 3-4 bad reactions with the biggest brands.
It's the reason we're here after all.
Also, check out CBD and brain repair or CBD and TBI.
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.