Is Tryptophan the Connection between Inflammation and Anxiety?
We're usually deep in NIH studies for about 1-2 hours a day for CBD.
We don't mind it.
We had to do this when perimenopause literally exploded our household and the benzos, SSRI's, and heart meds were about to kill us (literally).
Necessity is the mother of invention.
We had to research everything we could find for another solution.
This eventually led us to bioidentical hormones, CBD, and basic supporting nutrients.
That story is here.
So we're used to reading NIH studies on this and that variable with CBD.
Neurogenesis. Inflammation. Microglial activity. Brain tryptophan reduction in response to infection.
To backtrack...for a given subject matter, we'll usually go through about a dozen NIH studies.
Most of them are pretty familiar but every now and then, we stumble on one that makes our jaw drop.
Something that ties all the loose ends from the other articles.
The tryptophan article was such a case.
What we found may be the missing link between stress, inflammation and mental health issues (to begin with).
We'll get into it but why does it matter? What does it have to do with CBD?
Inflammation is the topic de jour for anything health related.
More specifically, there's a new study almost weekly about bacteria ending up some place in the body that it's not welcomed and a resulting auto-immune reaction wreaks havoc!
- Mouth bacteria lined in your arteries (not cholesterol from your liver or animals)
- Gut bacteria in the brain for Parkinson's
- Bacteria that's affecting colon cancer
- Inflammation tied to mental health issues such as anxiety, depression, and more
We finally have the technology to study this stuff!
So we're winding through our article on CBD, inflammation, and anxiety when we stumble upon it.
Let's get into that now and see if you geek out as much as we did.
We'll cover these topics.
- The research on tryptophan and inflammation
- How this tryptophan and inflammation affects anxiety and other issues
- How CBD affects this tryptophan and inflammation effect
Let's start with the study.
The research on tryptophan and inflammation
We'll walk you through the key steps and why it matters.
First, upon first sight of infection in the brain or nervous system, our body responds by reducing the levels of tryptophan.
Tryptophan is a key amino acid that we use to build all types of cellular material in the body.
The body does this to thwart the attacking bacteria, virus, or foreign invader.
It turns out that they also use tryptophan to make more of themselves!
It's a defense mechanism that evolution has stumbled on to make it harder and slower for them to reproduce.
This gives our defense mechanisms (immune response, cytokines, microglia, etc) a jump on the attacker (hopefully).
This begs the question for us...what does tryptophan do in the body (besides as a raw material to make us!)?
That's where things get so interesting for mental health issues including anxiety and depression.
How this tryptophan and immune response affects anxiety and other issues
There are two net effects of this drop in tryptophan available to our brains (with lots of others in the body).
- We lose energy levels since tryptophan is used to make NAD+ (energy source)
- Serotonin levels drop (ding ding ding!!)
Both are pretty impressive but the latter drives mental health!
First, the NAD+ effect.
Forget sugar, protein, and dietary energy.
When you go down the scale, NAD+ is the root source of all our energy.
It's the smallest bit of energy we have at the cellular level.
It powers everything in you right now!
Interestingly, tryptophan is the primary source of NAD+ synthesis.
When tryptophan drops, NAD+ drops.
Not only does cellular housekeeping drop but you generally feel lethargic and tired.
Sound like the flu?
By the way, you can now buy NAD+ as a supplement.
What about the connection between immune response and tryptophan for anxiety?
There's another important product that comes from tryptophan.
Serotonin is produced via the 5HT pathway.
That's short for 5-hydroxytryptamine
See that "trypt" in the end there.
Yes, serotonin is directly derived from tryptophan.
Why is serotonin important?
It might be the most powerful neurotransmitter in the nervous system (and body).
It really is the workhorse of signalling between neurons, within neurons, and across brain regions.
On a side note, tryptophan is also essential for producing:
- Melatonin (required for sleep) which is metabolized from serotonin
- Vitamin b3 - a host of functions including DNA repair!
- Auxins - may positively impact glucose balancing, anti-tumor effects, and neuro-inflammation
Back to serotonin.
Serotonin is also called the 'feel good" chemical in the brain.
This may be due to the fact that having too little or too much feels really bad.
Too little is tied to depression and partially, to anxiety (as well as most major mental health issues).
Too much (such as with serotonin syndrome from SSRI's) can be equally debilitating.
Medications that boost levels of Serotonin make up the lion's share going forward with SSRI's (see comparison of CBD and SSRI meds here).
Although benzo's effect on GABA levels is a more directly lever for anxiety, SSRI's clearly show results (if temporary) for anxiety with some people.
More importantly, let's look at the tie between tryptophan and anxiety.
By knocking out specific genes in the tryptophan pathways, researchers were able to cause anxiety-like behavior in mice:
Tryptophan 2,3-dioxygenase is a key modulator of physiological neurogenesis and anxiety-related behavior in mice
In another study on people, researchers submitted test subjects to oxygen deprivation.
Some of them had a placebo while others received a supplement dose of tryptophan.
The ones without tryptophan had a much stronger anxiety and panic response to the stressful event.
Furthermore, a significant increase in neurovegetative panic symptoms occurred after the CO2 challenge.
They went on to say…
We conclude that the serotonergic system is causally involved in anxiety-related mechanisms and that it may be worth pursuing the role of tryptophan depletion on CO2-induced panic in patients with anxiety disorders.
Their goal was to tie serotonin function to anxiety via tryptophan since it's the primary ingredient in that pathway.
It's not just anxiety though:
A diet that’s deficient in tryptophan reduces serotonin production in the brain and can lead to depression, anxiety, mood disorders, insomnia, poor cognition, and other brain conditions.
This speaks to the power of serotonin which has a range of effects in the body and brain.
As with all things, the gut microbiome figures greatly with serotonin levels.
In fast, most of our serotonin is made by gut bacteria!
Researchers introduced bifido bacteria (tied to improved states for anxiety via GABA production) and it increased serotonin levels:
Oral ingestion of a bifidobacterium by conventional Sprague Dawley (SD) rats resulted in evidence of changes in serotonin metabolism in the brain stem
More specific to our discussion L Reuteri (another bacteria) was shown to use tryptophan in the gut to affect anxiety:
L. reuteri co-operated with dietary tryptophan to make the important DP IEL cells.
Reuteri has been known to cause anti-anxiety effects and the above mechanism may be part of this:
Probiotic intervention reduces anxiety-like behaviors and systemic IL-6.
We have to get back to our topic or we could fall further down the gut bacteria effect on anxiety rabbit hole!
More information on CBD and gut bacteria here.
So to recap…
- The brain/body drops tryptophan production to thwart bacteria, virus growth
- Tryptophan is main ingredient for serotonin and NAD+ (our cellular energy source)
- Reduced serotonin has ancillary effects on anxiety (GABA is primary)
The new research is pointing to inflammation as being a lead factor in mental health issues such as anxiety and depression.
Perhaps, we just unraveled the primary mechanism!
Chronic inflammation would result in chronically reduced serotonin and energy levels not to mentioned the collateral damage of our immune response on healthy brain mass!
More here on the relationship between tryptophan, serotonin, and mood.
Finally...so what does CBD have to do with any of this?
How CBD affects this tryptophan and inflammation effect
CBD has shown to directly affect not only serotonin pathways but tryptophan itself.
Let's look at both.
The body has checks and balances that both encourage more production of a given chemical (such as tryptophan) and breaking it down when excessive.
That's where the endocannabinoid system usually comes into play.
It's a great balancer of many different chemical pathways.
In the case of tryptophan, there's a chemical called IDO ( indoleamine-2,3-dioxygenase) that breaks down tryptophan.
The endocannabinoid controls this process as CB1 and CB2 receptors were needed for the process.
CBD has been shown to directly support the endocannabinoid system.
So what does CBD do in this case when tryptophan is running low?
cannabidiol modulate mitogen-induced tryptophan degradation
The net result…
suppression of tryptophan degradation by cannabinoids via indoleamine-2,3-dioxygenase, which is independent of cannabinoid receptor activation, might enhance the availability of tryptophan for serotonin biosynthesis and consequently can be important in the action of cannabinoids to improve mood disturbances.
To translate this...CBD calmed the process that breaks down tryptophan.
Remember that chronic inflammation is our goal here for anxiety.
What about serotonin and CBD?
It has a direct effect there as well.
In fact, the endocannabinoid system is intimately linked to balancing this key system.
The eCB-induced modulation of stress-related behaviors appears to be mediated, at least in part, through the regulation of the serotoninergic system.
Endocannabinoids were even found as crucial in the area of the brain that releases serotonin in response to stress:
The glucocorticoid-induced inhibition of glutamatergic transmission was mediated by the activation of postsynaptic G-protein-coupled receptors and signalled by retrograde endocannabinoid (eCB) messengers
This sounds pretty confusing but to translate.
Stress chemicals tell the serotonin production area of the brain to ramp up VIA the endocannabinoid system!
Remember...it's tasked with balancing neurotransmitters!
What about CBD and serotonin?
The jury is in:
Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.
Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain.
Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels
That's a smattering of a host of different studies on CBD and serotonin.
We'll have much more discussion in our CBD versus SSRI's article.
Again, serotonin is not a direct target for anxiety (GABA is) but if it's levels are knocked from inflammation and immune response (via the tryptophan pathway we just layed out), anxiety can result.
Learn all about CBD and GABA support here.
You could argue that anxiety is more a symptom of inflammation!
We'll let the researchers sum it up:
Thus, the compensation of tryptophan degradation might be an important mechanism, by which THC and CBD may improve mood disturbances and quality of life, especially in diseases associated with inflammation.
Just a note...social anxiety may partially be a result of TOO MUCH serotonin.
Check out CBD and social anxiety here!
Okay, we're done geeking out. Till next time!