CBD and the Pathways of Brain Fog
February 15, 2022
During a brutal perimenopause, I was standing in the aisle at Safeway. Here for story on the brutal perimenpause.
Just staring at the wall of products and completely forgetting what I was looking for.
It was actually pretty scary…my mind was working at 10% and I really thought it was early-onset dementia.
Little did I know that estrogen is a workhorse in the female brain and I feel better than ever now but brain fog is very unnerving.
The route to brain fog is many but the pathways are being teased out from research.
Brain fog is a common occurrence with many issues:
- Perimenopause and menopause
- Poor sleep
- Chronic stress
- Trauma
- Medications
- Infections (and yes, including that which shall not be named)
We're going to drill into the pathways that actually drive brain fog and then we'll look at CBD's effects on those pathways along with other tools.
What we'll find is a sea of inflammation, oxidative stress, and reduced transmission of key neurotransmitters.
The good news is that all of these can be directly and safely improved!
What we'll find is that these same pathways are key for dementia risks, mental health, and a range of issues.
Brain fog may be the canary in the coal mine!
Here are the topics we'll cover:
- A quick intro to brain fog
- Inflammation and brain fog
- Oxidative stress and brain fog
- The histamine connection and brain fog
- Neurotransmitters and brain fog
- The gut-brain connection
- CBD and brain fog
- Other tools to look at
- How much CBD for brain fog
- What's the best CBD for brain fog
Let's get started.
A quick intro to brain fog
The brain is a very complex system with an intensive energy usage profile.
So much can go wrong.
Brain fog is characterized by the following:
- Loss of cognitive ability
- Mental fatigue
- Issues with short term memory
A generally poorly functioning mental landscape!
We can glean clues from the common causes.
Let's look at those again.
Perimenopause and menopause
This includes the monthly cycle as well since progesterone and estrogen both plummet before the period.
Estrogen is a powerful supporter of serotonin, our primary mood manager.
It also had a side hustle of supporting BDNF, the brain's fertilizer. BDNF grows, repairs, and reconnects neurons and brain areas.
We did a deep dive on BDNF here since it's the secret weapon with both mental health and addiction.
On the flip side, progesterone calms our brain's immune system and inflammation. It also supports GABA, the brain's "brake" pedal (target for benzos and alcohol - see CBD versus benzos).
GABA is key to keeping excess glutamate in check which is important since glutamate can literally kill neurons when too high. Glutamate is a net result of brain inflammation as well.
Testosterone is the male equivalent of estrogen and it drops about 1% each year from about age 20.
Testosterone also drives serotonin and BDNF.
All these hormones affect sleep quality and architecture. Let's go there now.
Poor sleep and brain fog
Brain scans of people with sleep deprivation are eerily similar to those in extreme anxiety!
Loss of sleep = brain inflammation:
Controlled, experimental studies on the effects of acute sleep loss in humans have shown that mediators of inflammation are altered by sleep loss. Elevations in these mediators have been found to occur in healthy, rigorously screened individuals undergoing experimental vigils of more than 24 hours, and have also been seen in response to various durations of sleep restricted to between 25 and 50% of a normal 8-hour sleep amount.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548567/
Studies show elevation of CRP and IL6 (two inflammatory markers) from short and long-duration sleep disruption.
Make a note on those two…we'll see them later.
During sleep, our brain cleans out waste products (oxidative stress, malformed proteins and cellular machinery, etc) in waves via the lymphatic system.
Not being able to clean this up is a huge source of brain fog.
Then there's the stress piece.
Chronic stress and brain fog
Stress is important but in short (and remediating) bursts.
Cortisol, our primary stress hormone is there to turbocharge the brain into action but like redlining an engine, too much for too long is destructive.
Animal and human evidence demonstrates that glucocorticoids (GCs), the main class of stress hormones, are strongly linked to memory performance whereby elevated GC levels are associated with memory performance decline in both normal and pathological cognitive aging.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619133/
So… longer-term stress starts to drive poor cognitive function.
This is pretty obvious to most people. We've all been there. "Frazzled".
What about acute stress…trauma?
Trauma and brain fog
Psychological trauma causes a shift of different brain parameters tied to brain fog.
It upregulates brain inflammation and downregulates serotonin and GABA (at a minimum).
This can even be early trauma with effects long into adulthood.
We covered early trauma and mental health here. It's so important since we're all walking around with something.
The signs are found across the brain:
Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors
There's the cortisol (stress) piece. Norepinephrine is adrenaline.
Brain areas are even affected:
Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181836/
Okay…the hippocampus is in charge of memory and mood. The prefrontal cortex??
Oh just thinking…cognition. Planning and rational thought.
The amygdala is your emotional system tied to fear.
We did deep dives on those at our anxiety review and depression review since the long-term effects of inflammation, trauma, etc cause an imbalance in the crosstalk between the prefrontal cortex and the amygdala with both.
Check our review on the hippocampus to learn how to support it.
We also did a deep dive on PTSD here.
Next up…medications.
Medications and brain fog
There is a range of drugs that can cause brain fog:
- 1. Antianxiety drugs
- 2. Cholesterol drugs
- 3. Antiseizure drugs
- 4. Antidepressant drugs
- 5. Narcotic painkillers
- 6. Parkinson's drugs
- 7. Hypertension drugs
- 8. Sleeping aids
- 9. Incontinence drugs
- 10. Antihistamines
When you dig into them, we see two common pathways:
- Acetylcholine - our alert but calm neurotransmitter (more on that below)
- Glutamate - our brain's "gas" pedal
We'll get into these and more below.
We're getting closer. Let's turn to infection and illness
Infections (and yes, including that which shall not be named)
Outside of neurotransmitters being out of sync, brain inflammation is the big star of the brain fog show.
The immune system is fascinating in the brain.
We think of it in terms of fighting infection but it does so much more upstairs.
Microglia, our key brain immune sentinel, is in charge of repairing, tearing down, and actually guiding brain architecture.
It manages the BDNF we noted above. It also can spill out glutamate.
The immune system is the future of mental health (see here).
The key output of the immune system from infection is inflammation.
Inflammation is a general term but there's a multitude of actors called cytokines that are specialized to attack foreign invaders.
After infection, there are elevated markers of cytokines in the brain and spinal column:
Levels of IFN-β and IL-8 are specifically enriched in the CSF compared with plasma
https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00051-9
That's tied to the current infection du jour but it holds true for all infections…elevated brain inflammation.
Our brain tries to starve out the bacteria/virus by downregulating tryptophan (an essential amino acid pathogens use to make more of themselves).
The problem is that tryptophan feeds serotonin which feeds BDNF!
That's the mental fatigue and low mood you feel when sick. We looked at it in detail here since illness is a big driver of brain fog.
Specific examples abound such as rheumatoid arthritis (see review on RA here).
Swain and his team found that inflamed body tissues (in this case, inflamed livers) transmit signals to the brain that can produce symptoms such as malaise and fatigue. Swain explains that chronic inflammation can “activate” immune cells in the bloodstream, causing them to enter the brain and release proteins called cytokines.
http://blog.arthritis.org/rheumatoid-arthritis/rheumatoid-arthritis-brain-fog/
There's a fascinating section in The Inflamed Mind by Bullmore where RA patients given medication saw their moods significantly brighten. The nurses loved giving out the meds.
A range of illnesses can drive brain fog but they all have one thing in common…elevated inflammation states.
We're going to leave histamine to its own section since it's so important.
Okay…let's drill a level down…it will help us understand the tools and what they do better.
Inflammation and brain fog
Inflammation is a generalized response by the immune system. Usually, infection or pathogens from outside are the culprit but not always!
Inflammation can be a response to stress, psychological trauma, injury, and even sugar!
There's a direct tie between brain inflammation and brain fog.
A study actually zoomed into which "circuits" of the brain were directly impacted in terms of brain fog following a typhoid vaccine:
The results showed that inflammation specifically affected brain activity related to staying alert
https://neurosciencenews.com/inflammation-mental-sluggishness-15212/
Alert here means…ready to take in and process information. The opposite of brain fog.
A big part of this has to do with how the brain tries to starve out bacteria/viruses of tryptophan to slow their replication:
Cytokines also activate the kynurenine pathway which not only depletes tryptophan, the primary amino acid precursor of serotonin, but also generates neuroactive metabolites that can significantly influence the regulation of dopamine and glutamate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141874/
Remember, cytokines are the little weapons of inflammation.
Goodness…serotonin is your driver of BDNF. Dopamine is your motivation/learning circuit. Glutamate is literally the "gas" pedal that makes the brain run.
There's another type of inflammation we have to discuss for brain fog. Oxidative stress.
Oxidative stress and brain fog
Mitochondria are little power plants that produce all the energy for everything you're doing right now.
They're actually ancient bacteria we took hostage (or invited in) almost 1 and ½ billion years ago.
Making energy is a very dirty business…even in the living beings.
The primary waste product from our energy production is in the form of oxygen. The "oxidants" in antioxidants.
Oxygen is like little molecules scissors in living tissue…it will slice and dice anything it comes in contact with including neurons and even DNA.
We have elaborate systems to keep free-floating oxygen at bay with glutathione being a big one. (see CBD and glutathione or CBD and oxidative stress).
Many things can spike oxidative stress in the brain (a hungry energy user) and the net effects of this are front and center for brain fog.
A powerful example of this is the so-called "chemo brain" tied to cancer treatment:
In rodent models, both the acute and repeated administration of doxorubicin or adriamycin (anthracyclines) or cisplatin impairs cognitive functions, as shown by their diminished performance in different learning and memory behavioral tasks.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301189/
Most importantly, giving powerful anti-oxidants can counter both the stress and the resulting cognitive issues! We'll get into those with our tool section below.
The brain fog tied to obesity and diabetes very much centers around oxidative stress as well since the whole complex is tied to energy system imbalance!
Based on the complex interplay between adipokines, obesity is also characterized by chronic low-grade inflammation with permanently increased oxidative stress (OS)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307252/
We looked at how excess sugar exhausts a key conversion pathway called the polyol pathway which results in nasty metabolites which eat up glutathione, our primary anti-oxidant and detox weapon.
Learn more about oxidative stress here but understand, it's part of the immune system so just a different type of inflammation.
One more "arm" of the immune response…a big one for brain fog.
The histamine connection and brain fog
Histamine is the key behind the allergic reaction but it's so much more than that.
It has a side hustle in the brain as an excitatory agent!
In fact, it opposes GABA (brain's "gas" pedal) tied to sleep and calm for the sleep/wake cycle (along with cortisol).
Just think of the effect from anti-histamines…pretty similar to brain fog.
But…it needs to stay in a tight range. Too much also is tied to brain fog!
Histamine can set off the whole inflammatory party:
Brain “fog” may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation (3).
Mast cells are where histamine gets released from. We did a major review of CBD and mast cells here.
Microglia are the brain's immune system sentinels. A call to war if you will.
Alright…let's finally turn to the neurotransmitters at play. We're getting there.
Neurotransmitters and brain fog
First the tie between everything we talked about (inflammation essentially) and the cogs of brain function (neurotransmitters):
a long-term increase in serum concentrations of proinflammatory cytokines increase the uptake and breakdown of monoamines (serotonin, noradrenaline and dopamine).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827268/
Even short term, inflammation interferes with their signaling.
We'll focus on the heavy hitters:
- Serotonin
- Dopamine
- Glutamate/GABA
- Acetylcholine
- Norepinephrine
They all interplay as well but let's do a quick summary because we can actually affect these.
Serotonin and brain fog
Serotonin is your master regulator of all human behavior. There's a clear tie-in with depression (the BDNF effect - see how SSRIs really work).
Depression and brain fog share a common thread:
- BDNF (and a share correlation)!!
No Wonder:
Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591905/
This is more of a long term element (takes about 2 weeks to start driving neurogenesis).
We have a big review on serotonin here.
The short effect is its effect on dopamine. Serotonin directly manages dopamine.
Let's go there.
Dopamine and brain fog
Think of dopamine as a lens that focuses your attention on what's important and then drives the brain towards that goal.
It's the learning and attention player with key ties to addiction as well (learning of sorts…just chemically induced).
The connection:
astrocytes produce kynurenic acid that acts as an antagonist on the α7-nicotinic acetylcholine receptor to inhibit dopamine release.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827268/
Goodness…the immune system (astrocytes) showdown acetylcholine to reduce dopamine.
That "can't get up in the morning" feeling.
See our big review on dopamine.
Speaking of acetylcholine…
Acetylcholine
Acetylcholine doesn't get the respect it deserves.
It's your alert and calm player.
Think of nicotine. Nicotine fits right into the acetylcholine receptor (with a hit on dopamine to lock in addiction).
If you're drawn to nicotine, you may want to look at supplementing choline (more on that later).
Ties with obesity and dementia to acetylcholine are front and center.
First:
Loss of cholinergic neurons is associated with impaired cognitive function, particularly memory loss and Alzheimer's disease (AD).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252552/
The risks of dementia go up with medications (even simple over the counters like antihistamines) that rip acetylcholine. Many drugs do this in fact.
And obesity also comes into play…
Dietary choline is related to neural efficiency during a selective attention task among middle-aged adults with overweight and obesity
"Selective attention". The opposite of brain fog.
See our Acetylcholine review here.
Okay…what about the gas/brake pedal of the brain?
Glutamate/GABA
First, GABA's effects are obvious - just look at the mental function with benzos and barbiturates.
See CBD versus benzos here.
Just look at the cognitive effects of benzo use (up GABA; down glutamate):
The results of the analysis for current users revealed statistically significant, negative effects for the cognitive domains of working memory, processing speed, divided attention, visuoconstruction, recent memory, and expressive language.
https://pubmed.ncbi.nlm.nih.gov/15762814/
They build tolerance and are incredibly addictive but clearly too much GABA can result in brain fog.
Too much glutamate isn't the right course either!
Remember, heightened inflammation in the brain drives excess glutamate which is toxic to neurons and their communication.
We have big reviews on GABA and glutamate separately. Balance is the key and we'll look at the systems that balance here and also keep glutamate under check below.
Finally….adrenaline (by any name).
Norepinephrine
We think of norepinephrine (adrenaline) in terms of fight or flight…a shocking effect.
In smaller doses, it's key to being engaged mentally:
norepinephrine is now recognized as a contributor to various aspects of cognition, including attention, behavioral flexibility, working memory, and long-term mnemonic processes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450174/
It's the "N" in SNRIs (which build tolerance, similar to SSRIs).
Again, too much of this is read as stress and causes inflammation so range-bound with such powerful players.
Just remember the mother of them all:
Serotonin does not therefore stimulate the brain; it instead balances out the excessive excitatory effects of other neurotransmitters.
https://www.simplypsychology.org/what-is-serotonin.html
One more stop (we promise).
The gut-brain connection
The gut acts as an inflammation thermometer for the rest of the body and the brain.
Its primary connection with the brain is the vagus nerve which just happens to be where acetylcholine is released (go figure).
Find me an issue or cause of brain fog that doesn't result (or start) with gut issues.
- Obesity. Check
- Chemo. Check
- Autoimmune. Check
- Mental health issues. Check
- HIstamine response. Check
See CBD and gut inflammation or CBD and the gut barrier to learn more.
The connection is finally being teased out:
through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behavior, with recent evidence that changes in behavior alter gut microbiota composition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879184/
Let's take one example with an issue that directly ties to brain fog…obesity.
recent reports suggest that neuroinflammation is an important causal mechanism in cognitive decline. This inflammatory status could be triggered by changes in the gut microbiota composition.
https://pubmed.ncbi.nlm.nih.gov/29107872/
Gut bacteria driving brain function and fog?
How?
The gut bacteria are powerful managers and even producers of neurotransmitters…like the ones we discussed above for brain fog.
bacteria have been shown to produce and/or consume a wide range of mammalian neurotransmitters, including dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005194/
Did we just list off the key neurotransmitters tied to brain fog?
Goodness.
A study on cirrhosis found specific gut bacteria tied to brain fog:
Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345956/
This is a brand new frontier in brain health…at the gut level.
We have to look at fixing the gut alongside the brain…they're the same thing!
Finally…we set the stage.
CBD and brain fog
First, a quick intro.
CBD works to support our natural endocannabinoid system.
This system dates back about 600 million years and is tasked with balancing other key systems such as:
- Endocrine system - hormones like cortisol and steroids
- Nervous system - neurotransmitters and pro-growth players
- Immune system - the brain's architect and manager of inflammation
I think we've stumbled on the intersection needed for brain fog!
This system can get taxed by stress, trauma, infection, pain, and various insults.
The beauty of CBD versus its cousin THC is HOW it works.
CBD is called an allosteric modulator which means it works like a feedback system.
It supports key pathways when running low.
Serotonin, GABA, and inflammation pathways figure strongly in our discussion.
Let's dive into CBD's role on these topics zooming out with each step:
- CBD and serotonin for brain fog
- CBD and GABA/glutamate for brain fog
- CBD and dopamine for brain fog
- CBD and neuroinflammation for brain fog
- CBD and oxidative stress for brain fog
- CBD and gut inflammation for brain fog
- CBD and histamine for brain fog
- CBD and cognition for brain fog
- CBD and brain fog for brain fog
Let's get started!
CBD and serotonin for brain fog
We've looked at CBD versus SSRIs (which boost serotonin in one direction) or CBD and serotonin directly.
CBD supports serotonin function when LOW!
This is so important since serotonin is range-bound to feel right. Too little or too much can be brutal.
Just ask people trying to wean off of SSRIs (see how we got off of SSRIs).
Our favorite study is this one (of many).
The injury was induced to animals which lead to increased pain sensitivity, anxiety, and faltering serotonin function.
CBD's effect:
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/
Analgesia is pain reduction.
5HT1A is a powerful serotonin receptor.
The word "rescue" is the most important. It is supported when low but doesn't push further…otherwise we would see serotonin syndrome (see serotonin syndrome) at higher doses.
We don't. This is pretty amazing and speaks to the underlying system…the endocannabinoid system which is tasked with BALANCING.
The effects of this boost to serotonin are seen directly in the brain. We'll get into that in the cognition section below.
What about the excitability balance?
CBD and GABA/glutamate for brain fog
One of CBD's most powerful effects is to support GABA (brake pedal) under excessive glutamate (gas pedal).
Too much glutamate is indeed toxic to neurons, communication, and brain function.
We've gone deep into this pathway at CBD and anxiety, CBD and sleep, or CBD and GABA.
See a pattern there?
CBD has multiple targets, but one aspect of its polypharmacy may be to help regulate excitatory glutamate (E) and inhibitory γ-aminobutyric acid (GABA) (I) transmission, which may influence the activity of excitatory and inhibitory signaling pathways
https://www.nature.com/articles/s41386-019-0333-8
Interestingly, a study of CBD and GABA looked at autism directly where GABA/glutamate patterns are flipped.
CBD positively affected this!
CBD increased subcortical, but decreased cortical, Glx. Across regions, CBD increased GABA+ in controls, but decreased GABA+ in ASD; the group difference in change in GABA + in the DMPFC was significant.
https://www.nature.com/articles/s41386-019-0333-8#
CBD actually calmed GABA function in the prefrontal cortex (the heart of cognitive functioning) for people with autism.
This is fascinating since the effect depended on the state of the brain and even brain areas.
The autistic brain needed more "engine" in the thinking area where it was depressed (not enough glutamate).
Speaking of which.
CBD and dopamine for brain fog
Dopamine is our reward circuit but its effects are many and varied.
It drives focus and action (literally…our motor controls are tied to its function - see CBD and Parkinson's).
Many anti-psychotics will just pound dopamine (or boost) it in one direction but this can have very different results depending on the brain area.
Huge dysfunction in sleep is a perfect example. Too much or too little.
A study looked at CBD and schizophrenia.
Schizophrenia is so difficult to treat because we actually have too much dopamine in one area (striatum) and too little in another (prefrontal cortex).
This leads to the "positive" symptoms (paranoia, hallucinations, etc) and the "negative" symptoms (depression, low affect, etc).
In a double-blind placebo study, CBD was as effective as the antipsychotic amisulpride but with a superior side effect profile (the sleep, brain fog, etc issues).
What about Parkinson's and CBD?
Parkinson's is characterized by a loss of dopamine neurons and function.
An animal study for Parkinson's looked at CBD's effect:
In addition to preventing the loss of dopaminergic neurons—assessed by tyrosine hydroxylase immunostaining –, the administration of CBD after 6-OHDA injury attenuates the activation of microglia in substantia nigra
https://www.frontiersin.org/articles/10.3389/fphar.2018.00482/full
The microglia piece there is probably the most important. CBD calmed the immune system from attacking dopamine-producing neurons.
What a great segue.
CBD and neuroinflammation for brain fog
Brain fog can probably best be characterized as trying to drive a car when it's on fire.
Of course, nothing's going to work!
In this case, the fire is inflammation, a key weapon of the immune system.
Stroke or ischemia in the brain is a 4 alarm fire.
Studies looked at CBD's effect after stroke:
Short-term CBD 10 mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO.
https://www.sciencedirect.com/science/article/abs/pii/S0278584616302524
Let's break that down.
- Cognitive impairment. Hello….brain fog!
- Calmed hippocampus reduction. Remember, this is the heart of memory.
- White matter injury - the communication tracts in the brain.
- Calmed immune response (glial)
There are many studies like this dealing with sepsis, stroke, blood brain barrier.
Speaking of which…
Several findings indicate that CBD can modify the deleterious effects on BBB caused by inflammatory cytokines and may play a pivotal role in ameliorating BBB dysfunction consequent to ischemia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150944/
This is important since the blood-brain barrier is the thin separation between our most precious real estate and the pathogens or chemicals that get into our bloodstream.
Check out CBD and blood-brain barrier or CBD and neuroinflammation to learn more.
The other big danger is our skull.
CBD and oxidative stress for brain fog
If you asked up, Indigo…what's THE main drive of brain fog?
If we had to pick one, we would probably say oxidative stress.
This is the waste product of our immune system and it's so destructive when not kept in check.
CBD is a powerful antioxidant in its own right:
CBD exhibits much more antioxidant activity (30–50%) than α-tocopherol or vitamin C [4].
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
There goes Vitamin C and E, well-known anti-oxidants
Then there's THE powerhouse detox pathway in our body and brain, 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 control
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
Peroxidase and reductase break down glutathione.
Finally, a study looked at oxidative stress damage caused by amphetamines:
CBD also protected the brain against oxidative protein damage caused by D-amphetamine in a rat model of mania
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023045/
Let's head down south.
CBD and gut inflammation for brain fog
We have a massive review of CBD and gut inflammation here.
Many studies but this one is very relevant on people with colitis, an inflammatory disease of the gut with known cognitive add-ons:
CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/
Gliosis is an inflammatory over-response
LPS is the signature of bacteria that our immune system reacts to.
Okay…so CBD calms gut inflammation…what does that have to do with brain fog?
The gut is the inflammatory thermometer for the brain!:
Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232190/
To translate, the nervous system takes its immune cues from the gut!
This makes sense. There's no direct line into the brain from outside. The gut is the primary contact with pathogens that might do us harm and if the alarms goes off there, it sends a corresponding signal to the brain…headquarters if you wil
We're getting closer…one more stop that no one is talking about.
CBD and histamine for brain fog
We know that a little histamine is good to keep you engaged but too much is very bad for brain function.
Histamine is released from mast cells, a specific type of immune system that responds to foreign or bad actors that gain access to our body or brain.
CBD's effects are pretty well established in states where the response is too heightened (asthma, etc):
Together, the results suggest that CBD may induce activation of PPARγ in mast cells leading to secretion of G-CSF and consequent MDSC mobilization.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433789/
MDSC are special cells that put a check on mast cells.
Remember that progesterone (for women) is a powerful histamine calming agent and it drops by 50% at age 40.
See progesterone review to learn more.
We also did a deep dive on mast cells and allergic reactions separately.
Finally, let's turn to cognition…the opposite of brain fog.
CBD and cognition and brain fog
First, the basics. How does CBD affect thinking and brain function in general?
In healthy volunteers, acute CBD enhanced fronto-striatal resting state connectivity, both compared to placebo and THC.
https://www.frontiersin.org/articles/10.3389/fphar.2020.618184/full
Okay…so far so good, more connectivity in the key axis between thinking (frontal cortex) and motivation/focus (striatum where dopamine is king).
CBD went on to benefit people with autism, anxiety, and psychosis differently but positively in that study.
Many people think that CBD will slow down brain function because they associate with THC.
Couldn't be further from the truth. In fact, CBD counters many of the negative effects of THC (see CBD versus THC for more).
THC pushes CB1 (endocannabinoid receptor) in one direction where CBD supports when low.
Huge difference as can be seen by the side-effect profile and more importantly, tolerance.
CBD doesn't build tolerance!
The net effect:
CBD modulated brain activity and had opposite effects when compared to THC following task-specific patterns during various cognitive paradigms
We looked at CBD in the middle of the day to make sure it doesn't cause sedation or sluggish thinking (like THC).
A study that looked at CBD during wake periods:
Fifteen milligrams THC would appear to be sedative, while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC. D
https://www.ncbi.nlm.nih.gov/pubmed/15118485/
This directly opposes its benefits for sleep during dark periods.
The sleep/wake architecture is incredibly important for brain fog and CBD supports wakefulness during the day and sleep during the night.
It's interesting to look at an issue that directly drives brain fog to gain clues.
Social anxiety is a perfect example?
Think…when you're incredibly nervous…what happens to brain function? Memory. Thinking. Verbal skills.
All out the window.
A study looked at public speaking for people with diagnosed social anxiety (talk about torture).
There was a healthy control group (HC). An anxiety group without CBD. An anxiety group WITH CBD.
The effects during public speaking:
No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079847/
Let's dissect this because it's too fascinating.
CBD essentially normalized cognitive abilities (memory, recall, verbal, etc) to that of healthy controls when undertaking public speaking in people with diagnosed social anxiety!
Read that back over…it's a lot to unpack.
We did a big review on CBD and public speaking or CBD and social anxiety.
CBD is an absolute must if a person uses THC. See why here.
Let's turn to the hippocampus, the seat of our memory.
It's incredibly plastic (can change) and also as a result, susceptible to damage from stress, chemicals, trauma, hyperactive immune response, too much glutamate, etc.
The key there is neurogenesis or the repair/replenishment of its structure.
We did a deep dive on how CBD, exercise, and meditation can drive this but BDNF is the star player here:
Preclinical studies have shown CBD to induce synaptic plasticity and facilitate hippocampal neurogenesis,29,30 with some evidence suggesting that the proneurogenic action of CBD via the hippocampus may underlie its anxiolytic effects.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908414/
The hippocampus also acts as a management hub for our mood!
BDNF is our best defense against the assaults on our brain that can drive brain fog.
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/
There's that prefrontal cortex again. A reminder of its role:
The prefrontal cortex (PFC) plays a central role in cognitive control functions, and dopamine in the PFC modulates cognitive control, thereby influencing attention, impulse inhibition, prospective memory, and cognitive flexibility
https://www.sciencedirect.com/topics/medicine-and-dentistry/prefrontal-cortex
Put those two together now.
Alright, let's look at other supporting players for brain fog.
Other tools to look at
We've covered many pathways:
- Brain inflammation
- Oxidative Stress
- Gut inflammation
- Steroidal hormones
- Neurotransmitter imbalance
- Immune response
There are safe ways to support these pathways when under duress that do not cause tolerance!
Here are our favorites to use with CBD:
- NAC
- CDP Choline
- Magnesium glycinate
- Carnosine
- Vitamin D
- Berberine
Remember…these help but for women, estrogen and progesterone are the main players. We did deep reviews on those here and here.
There's no getting around them since you have receptors on every cell of your body…and brain!
A quick run-through.
NAC
NAC is a powerful antioxidant (that's one check). It also acts as a sink for excess glutamate which usually reflects a heightened immune response.
Huge studies on NAC and mental health and our full review is here.
The net net:
NAC as a precursor to the antioxidant glutathione modulates glutamatergic, neurotrophic, and inflammatory pathways.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967529/
Just look at the inflammatory disease, dementia:
Glutathione (GSH) is a major antioxidant, and it is already known that GSH is depleted significantly in the hippocampal regions in mild cognitive impairment (MCI) and AD patients compared to healthy old subjects.
https://pubmed.ncbi.nlm.nih.gov/30776003/
NAC is a powerful way to support glutathione. Full review here.
CDP Choline
Speaking of dementia, acetylcholine is a power player in the brain. We can supplement it with CDP Choline directly.
Eating eggs is also a good source! By the way, all your steroidal hormones are made from the so-called "bad" LDL cholesterol. Go figure…since they literally manage cardiovascular health and the heartbeat itself.
Studies are bearing this out:
Performance on the VM and VsM factors was better with higher concurrent choline intake in multivariable-adjusted models for VM
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252552/
Review on acetylcholine here. Glutathione gets eaten up by the gut pretty quickly. NAC can get through better.
Let's go minerals now.
Magnesium glycinate
Mag is amazing…it's a powerful supporter of GABA, a stress response buffer, and immune inflammation calming agent.
Many people don't get enough mag since it's transferred to food via bacteria/fungi in the soil.
Pesticides and monocrop rotations has destroyed that conveyor belt.
This is huge for sleep and anxiety states which are so detrimental to brain function (we've all been there).
Mag is a powerful stress response buffer. In the brain!
Look at the effect of too little mag:
hypomagnesemia has been associated with stressful conditions such as photosensitive headache, fibromyalgia, chronic fatigue syndrome, audiogenic stress, cold stress, and physical stress, amongst others.
https://www.ncbi.nlm.nih.gov/books/NBK507250/
Chronic fatigue is a veritable swimming pool of brain fog.
Full review on mag here.
Carnosine
Behind CBD, this is our favorite.
Like CBD, its effects are system-wide and ridiculously powerful.
Carnosine mops up the damage caused by sugar in the body. Sugar can stick to fat and proteins and cause them to malfunction. This accumulates.
The Amyloid-beta plaques in dementia? AGE's. Advanced glycation end-products are composed of cytokines (immune assassins).
This disrupts the energy production complex which leads to oxidative stress, less energy, and collateral damage.
End result:
Studies have suggested that an elevation of carnosine levels (or related dipeptides) in brain may improve cognitive function [23], mental fatigue [24] and memory [25], as well as ameliorate symptoms related to neurodegenerative diseases (e. g., Alzheimer's and Parkinson's diseases), epilepsy, and brain injury [42].
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123857
Full review on carnosine here.
Vitamin D
D is a master regulator of hormones and immune function. It's actually a steroid we get from the sun.
Problem is that roughly half of us are deficient and that's based on the requirement for bendy knees and rickets.
It's a powerhouse in the brain:
Many preclinical studies have supported the hypothesis that vitamin D leads to attentional, behavioral problems and cognitive impairment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210535/
It has the following characteristics:
Its neuroprotective, anti-inflammatory, and antioxidant effect on neurons promotes brain health [8–10]. Vitamin D promotes the production of neurotrophic factors such as nerve growth factor (NGF).
Get your levels checked! I have to take 10K daily just to get it over 50.
Let's turn to the other brain.
Berberine
Berberine is a fascinating supporter of gut health with a longevity kick (AMPK - see here) to boot.
The clincher:
Berberine can pass through the blood-brain barrier and has multiple pharmacological properties in the brain, including neuroprotective and neurotrophic effects.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055107/
But the gut is our focus since it drives inflammatory states in the brain via the vagus nerve.
The real driver appears to be changed to the microbiome, the bacteria that reside in our gut.
One final note before we jump off to practical questions on CBD.
Steroidal hormones. Estrogen. Progesterone. Testosterone. Brain fog is a huge complaint during perimenopause (as we discovered) and that's a period of estrogen flux and drop.
Read up on estrogen and mental health here. There's no getting around it. We address the safety piece here and here.
How much CBD for brain fog
Based on research, we actually have a range.
Peak neurogenesis (BDNF, brain repair) is around 300mg daily. That would generally mark the high limit for brain fog.
Studies on more severe issues (opioid withdrawal, psychosis, public speaking) were at 600-800mg daily so it's not a question of safety but the neurogenesis is key to how it works in the brain.
Down from there, 50mg is generally a wellness dosage but there will be effects on inflammation, stress response, sleep quality, etc.
So our range is generally 50mg - 300mg daily based on the available research.
A full dropper of the 6000mg bottle is 200mg. You can place under your tongue for up to 60 seconds to boost availability.
The neurogenesis piece builds over time (that is why it takes 2 weeks for SSRIs to kick in till tolerance takes over).
CBD does not build tolerance! See CBD and brain repair here.
What's the best CBD for brain fog
First, we need a really clean product:
- From organically grown hemp in the USA at FDA registered farms
- 3rd party tested
- CO2 cold-processed
- No THC (builds tolerance and actually reduces cognitive function)
- No Pesticides
- No Solvents
- No Heavy Metals
- No Mold
- No Bacteria
Our third-party testing is available at the top of each page.
Then, there's CBD isolate versus full spectrum.
All the research is on CBD by itself. Isolate. We follow the research (hopefully obvious by now).
More importantly, 40-60% of the population has histamine issues.
This number goes up as we get older and for women (progesterone leaving).
We see night-and-day differences in response between full-spectrum and isolate. Just look at what people say in the reviews.
Remember that histamine in the brain is excitatory and can actually cause brain fog when elevated.
Then there's cost.
We price our CBD at 2-3 cents per mg with the 6000mg bottle before discounts up to 50%.
Originally, we found CBD from a brutal perimenopause (that story is here - brain fog was a big part of it).
If we can help people feel better, it's worth 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.