There's new research on the genetic underpinnings of anxiety which is fascinating.
Individuals inherit a predisposition to being an anxious person, [and] about 30 to 40 percent of the variability is related to genetic factor
https://www.everydayhealth.com/news/is-anxiety-hereditary/
We can't pick our genes but genetics is only part of the equation.
Those genes are turned on and off constantly by our environment.
THAT...we can affect.
There are also ways to support or supplement gene variants we have to help offset negatives.
Take MTRR and MTHFR mutations for example.
Both are very common (roughly 40% of the population) and can have very pronounced effects on health.
They govern our ability to process (methylate to be exact) Vitamin B12, B6, and Folate.
We can take methylated B vitamins to offset this slowdown in genetic machinery.
Translation...check out your MTRR and MTHFR gene at 23andme or Stratagene!
What about anxiety?
Are there genes in play that we can support or offset?
Yes!
In fact, one of them is directly tied to CBD.
The link is fascinating….just check out the article on the woman who can't feel pain or anxiety here.
Needless to say, this is just a highlight reel of genes tied to anxiety.
It truly is the wild west...changing by the day...and with CRISPR, the ability to sub out bad gene variants is not as far off as naysayers warn.
We'll look at that one and other targets tied to anxiety to see what we can do.
Dr. Ben Lynch has a great book called Dirty Genes for common suspects tied to a range of health issues including anxiety.
Here are the topics we'll review:
- A quick look at how genes affect anxiety
- The endocannabinoid system and anxiety
- The FAAH gene variant and anxiety
- 5HT or Serotonin genes and anxiety
- BDNF gene and anxiety
- MAO gene and anxiety
A quick look at how genes affect anxiety
Our genetic makeup is just a blueprint...a book of instructions.
Based on environmental and outside influences, a specific cell may bounce around that book and read certain passages.
Genes are turned on and off in every cell millions of times a second.
In fact, a recent study compared the current state of genes that were turned on and off at a time between young and old cells.
Their goal is to see where they are different.
Again, both cells have the same genes...just some are being expressed more while others are being expressed less.
It's called the transcriptome and look for it to be the next leg in genetics following on the new revolution of "epigenetics".
We say all this to instill a bit of hope.
Our genes are not our destiny.
We can actively boost and suppress certain genes in many ways.
Let's look at anxiety in this regard.
If you're drinking energy drinks, taking stimulants, sleeping poorly, not exercising, etc...anxiety may be a result regardless of your genes.
A study found that sleep deprivation looks like intense anxiety when they scanned the brain:
When the participants were sleep-deprived, their anxiety levels increased by 30 percent the next day, with half the participants reaching the threshold for a clinical anxiety disorder.
https://www.popsci.com/sleep-deprivation-brain-activity
The MRI scans were even more interesting:
Following the night of no sleep, there was significantly more activity in emotion-generating regions of the brain, such as the amygdala and the dorsal anterior cingulate cortex.
If you've read our CBD and anxiety article, you'll recognize those brain areas (ad nauseum).
Estimates put the ratio at 50% genes and 50% environment.
They richly interplay with each other.
Environmental cues turn genes on and off. Heck...even our gut bacteria turn genes on and off in our immune system!
Conversely, genes drive certain environmental situations.
One of the smartest 19 years old I ever came across once told me…
"I'm an alcoholic...I've just never drank before".
He was 100% Cherokee and knows that he doesn't have a gene to breakdown alcohol.
It has ravished his whole family.
This an extreme example of how a gene can be powerful.
Are there such genes tied to anxiety?
Sure. Both directly and more subtly.
Let's take a look at some of those and more importantly...let's see if CBD can affect those pathways.
We'll start with the most fascinating one.
CBD and the FAAH gene variant and anxiety
We've written extensively about the woman who can't feel pain or anxiety (or depression for that matter).
She has a variant of a gene called FAAH.
Keep in mind that for many genes, there may be many different "flavors" based on mutation.
Some people may make too much FAAH while others make too little.
There could even be a range between the two.
So what is FAAH?
It's short for Fatty Acid Amide Hydrolase.
Guess what family it belongs to?
The endocannabinoid system!
That's our internal system that we all share with every living animal.
It dates back about 600 million years evolutionarily speaking.
This is the same system that CBD operates within. (first clue!).
What's the tie with FAAH and anxiety?
It's very direct.
In fact, too little FAAH activity and you'll never feel anxiety.
Too much, and you have "trait" anxiety even as a child.
This means the anxiety is partially a result of your genetics and not trauma, stress, or experience.
We all get anxious sometimes.
What if you have anxiety all the time...all your life.
That's trait anxiety. Check out CBD and general anxiety disorder and Could CBD and tryptophan be a stress reserve for social anxiety.
FAAH is powerful in two way:
- Neurotransmitter signaling on an ongoing basis
- Brain structure during key times of development within the "anxiety circuit"
Let's look at both.
Keep in mind that roughly 20% of the population has a variant here with "too much" FAAH (too much anxiety) being the default since many people do not survive having "too little" (no anxiety ever).
First, what does FAAH do on an ongoing basis?
It breaks down other cannabinoids...the key one for our discussion on anxiety is Anandamide.
Anandamide is the second most prevalent endocannabinoid in the brain and called the "bliss" molecule.
Higher levels are tied to calm and lower pain.
FAAH acts like a brake pedal on anandamide.
If it feels so good, why not just have higher levels of it!
When that bus is about to hit you, you would just smile and stare at it.
More importantly, your ancestor, would see the bush rattle and go reach in hand in there (only to be eaten by the tiger).
There's a direct tie with pain as well.
In the article about the woman who doesn't feel pain and anxiety, she has literally had her arm burn and not know it until she smelled burning flesh.
It's very dangerous to have zero FAAH.
Being overly anxious isn't dangerous from a survival perspective but it sure isn't fun either!
That's the ongoing signaling happening in your brain right now.
What about the effect of FAAH on the brain structure?
Here's where the anxiety circuit comes into play.
A study found that people with the lower FAAH gene variant had structural brain differences:
The results showed that the study participants who carried the gene variant had a stronger connection between their limbic and frontal brain areas, compared to those who carried the default gene. They also reported less anxiety.
https://www.livescience.com/54111-anxiety-risk-linked-to-gene.html
This is important for anxiety:
The stronger connection between frontal and limbic areas might mean that in these people, the frontal areas are better at regulating fear responses in the limbic areas, effectively controlling anxiety levels
This effect occurs during adolescence.
Before you add depression to anxiety over developmental "spilled milk", there's some good news there.
Check our article on three proven ways to strengthen brain area connections and signaling here.
CBD, mindful meditation, and exercise have been shown in research to actually thicken these key brain areas.
Read our article on CBD and meditation, exercise, and neurogenesis for anxiety.
See our article on CBD and brain repair.
We can repair the brain!
By the way, THC (the "high" part of cannabis) can cause damage to these same "anxiety circuit' pathways (see CBD versus THC for anxiety).
As for ongoing FAAH signaling, is there anything we can do there?
Yes!
Research is showing that CBD has a direct effect on both Anandamide and FAAH:
CBD inhibits both AEA hydrolysis by FAAH-containing membrane preparations (Watanabe et al., 1996), and AEA uptake by RBL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017/
Translation...CBD boosts anandamide levels by blocking FAAH activity!
This is thought to be one of its key pathways for helping with anxiety.
It's not the only one though!
5HT or Serotonin genes and anxiety
Another set of genes come into play with anxiety.
Genes that govern serotonin function.
Serotonin is a master signaler in the brain (and gut) as well as the target of the leading class of anxiety medications...SSRI's (see CBD versus SSRI's for serotonin).
GABA is the more direct lever for anxiety but serotonin's effect on anxiety may be indirect.
Serotonin is key to repairing and building new brain connections...a process called neurogenesis.
That's why it can take SSRI's a few weeks to even kick in.
You can learn all about the Serotonin transporter gene here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267339/
There's a known difference in serotonin function between two different "alleles" or flavors of the gene that a person may have:
The L allele confers a threefold increase in transcriptional efficacy and activity than the S allele.
Three-fold!
If you read through the above article in full (not an easy read), you'll see that the impact is more acutely felt with depression.
This is not surprising since serotonin is more directly impactful on depression and only secondarily associated with anxiety.
See CBD versus SSRI and serotonin and CBD versus Benzos for anxiety for a full walkthrough.
Where serotonin is important for many mental health issues is hippocampus neurogenesis.
We'll translate after:
One of the most important factors regulating proliferation in the DG is serotonin. Brezun and Daszuta (1999) 192 R.L. Djavadian found, that depletion of serotonin in the brains of adult rats decreased the numbers of the BrdU-labeled (newly generated) neurons in both SVZ and DG
https://pdfs.semanticscholar.org/195e/f2c59104aed40b466b26b4866307454ce021.pdf
SVZ and DG are two important areas of the hippocampus where neurons are formed.
Why does this matter for anxiety?
Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.
https://www.ncbi.nlm.nih.gov/pubmed/25833129
Put it this way...serotonin is so prevalent in the workings of the brain that lower levels can show in many different mental health issues including anxiety.
SSRIs, which boost serotonin come with a laundry list of side effects which isn't that surprising considering how many pies serotonin has its finger in.
Is there a way to more safely boost this pathway according to research?
CBD.
Some interesting experiments were able to tie CBD's effect on anxiety and depression to serotonin pathways directly:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
https://www.ncbi.nlm.nih.gov/pubmed/30157131
Allodynia is essentially a nervous system pain threshold.
What about the bigger piece for longer-term hippocampus neurogenesis with anxiety.
Does CBD help there?
Let's sum it all up with research here:
the anxiolytic effect of chronic CBD administration (14 days) in stressed mice depends on its pro neurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signaling
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648779/
Anxiolytic means anti-anxiety.
What's pro neurogenic?? A different way to say neurogenesis and there's the hippocampus in question.
See our article on Can CBD stimulate the hippocampus neurogenesis for anxiety.
CBD has the same effect on this circuit which makes sense since it boosts the serotonin pathway.
Check out how chronic stress can injure the brain and lead to anxiety here.
Speaking of repairing the brain.
CBD effect on BDNF gene and anxiety
BDNF is short for brain-derived neurotrophic factor (thank goodness).
BDNF is essentially a growth factor in the brain.
See our article on CBD and neurotrophins like BDNF.
It's instrumental in growing new brain tissue and connections.
We lose neurons all the time due to inflammation, immune response, stress, chemicals, etc.
BDNF is key to the neurogenesis process we mentioned with Serotonin above.
Read our article on CBD and meditation, exercise, and neurogenesis for anxiety.
Why does this matter for anxiety?
BDNFMet/Met mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1880880/
Interesting.
This may speak to the percentage of people that SSRI's do not have a positive effect on.
Fluoxetine is a popular SSRI.
More telling is that early life stress can reduce BDNF function later in life:
lack of mother-infant interaction during the late lactation period leads to an increase in corticosterone synthesis for 2 days and a decrease in BDNF synthesis in males; moreover, this lack of interaction transiently inhibits hippocampal cell proliferation and survival in both males and females, although the effects were more pronounced in males.
https://www.sciencedirect.com/science/article/pii/S0306453008003351
Stress is the enemy of BDNF and lack of neurogenesis which may lead to anxiety-like symptoms later in life.
Exercise is a powerful supporter of BDNF expression!
What else can we do to support the levels of BDNF?
Glad you asked!
Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex.
https://www.ncbi.nlm.nih.gov/pubmed/29869197
Other gene targets for anxiety
As we mentioned before, this is the wild west of health.
New information is coming out weekly and that will only explode once artificial intelligence is unleashed on our genome.
There are some usual suspects that manifest across a range of issues since they're such important genes:
- MAO - breaks down neurotransmitters
- COMT - breaks down stress hormones
- GAD2 - involved in GABA pathway - the key to anxiety
You can learn about other targets here:
https://biolmoodanxietydisord.biomedcentral.com/articles/10.1186/2045-5380-3-9
And here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573560/
The most fascinating one we found was the FAAH gene above.
First, the new research on the woman who CAN'T feel anxiety was solely tied to that gene.
Secondly, we know the mechanism behind it (increased anandamide) and we can actually mimic that effect partially through CBD.
FAAH speaks to the endocannabinoid system in regulating our response to stress!
Check out CBD, stress, and anxiety here.
The serotonin pathway is secondary...but powerful...especially for long term brain remodeling!
As new research comes online, we'll add it accordingly (if we can keep up with it!).
Anxiety was a driving force behind our creation of IndigoNauturals. That story is here.
We make every decision based on research since our whole family uses it.
Check out CBD benefits for anxiety for more information on the basic pathways of anxiety.
Feel better. Be well!
Check out:
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Master overview of CBD and anxiety pathways to look at various aspects we can directly affect.
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Links to CBD and anxiety research with dozens of anxiety-specific topics.
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.