CBD and Tryptophan: Stress Reserve for Social Anxiety?
February 07, 2020On our way through the research on CBD and social anxiety, we kept coming across really interesting pieces on another player.
Tryptophan.
Forget the myths about eating turkey (or any protein) for boosting its level or blaming it for making you tired at Thanksgiving.
There are interactions way more primal for tryptophan dealing with social stress, stress response thresholds, and even self-confidence!
Like we said...it's fascinating!
It also appears to be a marker from the past (social rejection) that can continue to affect how you feel about yourself or feel in general.
We're going to do a deep-dive on this as social anxiety is such a destructive force across the population.
These are the topics we'll look at:
- What does tryptophan do in the body
- Tryptophan and serotonin
- Tryptophan and earlier social rejection
- Studies on the effects of Tryptophan and anxiety, depression, and more.
- Tryptophan and inflammation
- Can tryptophan and CBD help with social anxiety
- What foods are high in tryptophan...does it matter?
- Does tryptophan make you sleepy
- Other ways to support the tryptophan serotonin pathway
Let's get started.
Not to be dramatic, but this may change a great deal of how you think about social status.
What does tryptophan do in the body
Tryptophan is an essential amino acid that the body uses to make various proteins.
Important ones like:
- Serotonin - a master regulator neurotransmitter (star of the show below)
- Melatonin - a key to sleep initiation and maintenance
- Niacin - a key B vitamin
Our body is unable to make tryptophan by itself so we have to take it in through our diet.
We'll get into the whole tryptophan through food question (the turkey lie!) below.
As we go deeper into the social anxiety piece, we have to really focus down on serotonin.
Let's go there now.
Tryptophan and serotonin
Tryptophan is the sole way we get serotonin.
The chemical name for serotonin is 5HTP (short for 5-hydroxytryptamine)
"Trypt" is right in the name!
Tryptophan is actually not terribly interesting (although essential).
Serotonin, on the other hand, maybe one of the most powerful pathways in our body, brain, and gut!
It's also the target (bullseye more like it) of SSRI's, the most prescribed medications on the market (see CBD versus SSRIs for serotonin).
It's commonly referred to as our "feel good" neurotransmitter but that's a misnomer.
The truth is probably closer to the fact that you'll feel really bad if it's too low (depression, constipation, etc) or too high (serotonin syndrome).
It is truly a master controller:
Serotonin has been implicated in practically every type of behavior, such as appetitive, emotional, motor, cognitive and autonomic.
https://www.ncbi.nlm.nih.gov/books/NBK27940/
Its function is too exhaustive (and nuanced) for this review so we're going to drill down into its effect on social status and social anxiety.
There are clear effects on mood and a sense of well-being.
Many studies have looked at this such as this one on HEALTHY volunteers:
A within-subjects analysis of the participants’ mood indicated significantly (p < .01) more positive affect scores after consuming a high tryptophan diet as compared to a low tryptophan diet.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393508/
"Positive affect" just means feeling upbeat.
Do you ever wonder what exactly makes us "feel' things about ourselves and even our place in a social hierarchy?
Confident. Insecure. Somewhere, deep down in the brain's architecture and chemical workstation (neurotransmitters), there must be levers.
Research is pointing to serotonin as a key lever in that seemingly inscrutable outcome.
Let's pull back the curtain.
I hope you geek out as much as we do.
We'll go back in time first. Early social rejection.
Tryptophan, serotonin, and earlier social rejection
We're usually diving deep into some pathway that CBD affects.
Why even write a full review of tryptophan and social anxiety?
Because of this study.
Researchers studied various primates, their social rank, and serotonin levels.
They found a direct correlation between serotonin and social rank.
In fact, when a power vacuum allowed another monkey to rise through the ranks, their serotonin level would go up accordingly (and the same is true for a drop-in social ranking).
We found that in male vervet monkeys, elevated blood serotonin concentration is a state-dependent consequence of the active occupation of the dominant male social position.
https://www.ncbi.nlm.nih.gov/pubmed/6703857
Various reflections of this have been found across species with the resulting statement:
The results suggest that 5-HT plays an important role in the regulation of individual behaviors that organize social group dynamics.
The net takeaway is this...serotonin acts as a reward system for social interaction.
But it can also act as a stick for social rejection!
It gets more nuanced which we'll come back to but let's go back to the early rejection.
A Dutch study called the Trails study looked at long term relationships between early social rejection and later serotonin function and anti-social behavior.
The results:
The interaction between 5-HTTLPR and preadolescent peer rejection predicted antisocial behavior with carriers of the 5-HTTLPR short-short variant most strongly affected.
https://www.rug.nl/research/portal/files/13522248/60.2.kretschmer.pdf
The fascinating piece was that this was (partially) driven by a genetic variation in the serotonin pathway.
After all, we all respond differently to social rejection or anything for that matter.
What's the net effect of this short-short flavor of this gene?
5-HTTLPR, with the 14-repeat short (S) variant having less transcriptional activity and lower serotonin uptake than the 16-repeat long (L) variant.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2841212/
Lower serotonin function.
So….if we have lower serotonin function (either due to genes or diet/health), we're more impacted by earlier social trauma or rejection.
Then, there's the wild study on psilocybin (the psychoactive chemical in psychedelic mushrooms).
It was able to "blunt" the effect of social rejection via the serotonin pathway:
In conclusion, 5-HT2A/1A receptor stimulation with psilocybin seems to reduce social pain processing in association with changes in self-experience.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983864/
This occurred in a key brain region that tied to anxiety and social pain processing called the dorsal anterior cingulate cortex (dACC) (check CBD and social anxiety or CBD and anxiety circuit).
Early social rejection can affect the stress "threshold" going forward which is key to anxiety in general.
Interestingly, early life stress, trauma, or infection can downregulate...serotonin!
See more on early trauma and serotonin.
Let's turn our attention to tryptophan.
Studies on the effects of Tryptophan and anxiety with a focus on social anxiety
There are lots of studies on "tryptophan depletion".
This is a great way to test the resulting effects on serotonin levels.
Interestingly, tryptophan does not result in depression in healthy individuals.
It does have interesting effects though.
Lowering brain serotonin using acute tryptophan depletion leads to an increased negative affective bias as a result of a change in the connectivity between mPFC and amygdala.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393508/
If you read our CBD and anxiety guide, you'll see these two brain areas make up the main "anxiety circuit" in the brain.
Negative affective bias just means the glass is half empty.
Let's look at some of the studies specific to social anxiety.
Tryptophan and Social Anxiety
One study placed volunteers under oxygen reduction (simulates choking or drowning - stressful) and tested their stress response to this:
There was a significant increase in anxiety on the Spielberger Anxiety Inventory and a trend towards more tension on the Profile of Mood States-`tension' items, both of which were interpreted as increased nervousness.
https://www.sciencedirect.com/science/article/abs/pii/S0165178198000043
This occurred in the group without tryptophan supplementation versus the other group which were given tryptophan prior to the test.
This points to tryptophan (and really serotonin) as a stress response "buffer" or "supply".
When it runs out, we're more likely to overreact. Panic is a perfect proxy for this effect.
Check out CBD and panic attacks for more detail.
Other scientists bred mice with reduced ability to process tryptophan.
They found a pronounced effect on anxiety and maybe, more importantly, neurogenesis (brain growth and repair).
This study is important as it illuminated the "pathway" by which tryptophan is tied to anxiety and neurogenesis.
These findings demonstrate a direct molecular link between Trp metabolism and neurogenesis and anxiety-related behavior under physiological conditions.
https://molecularbrain.biomedcentral.com/articles/10.1186/1756-6606-2-8
Check out CBD and BDNF or CBD and neurogenesis to find out why this is so critical to anxiety.
As we mentioned above, SSRIs directly stoked the serotonin pathway (which lies at the end of tryptophan) till tolerance builds up.
What about tryptophan depletion and SSRI function?
Great question.
Tryptophan Depletion Reverses the Therapeutic Effect of Selective Serotonin Reuptake Inhibitors in Social Anxiety Disorder
https://pubmed.ncbi.nlm.nih.gov/15450786/
Think how interesting that is...they can block the effects of SSRI's by reducing tryptophan.
Most importantly, this was in a group of people with a diagnosed social anxiety disorder.
Check out CBD versus SSRI's here.
Remember how serotonin is a master regulator of how we view our social situation (hierarchy, status, etc)?
That study looked at different tasks and the most difficult for people with social anxiety was the autobiographical task (speaking about yourself).
Their conclusion:
Tryptophan depletion induced a significant increase of anxiety in treated SAD patients, which was more prominent during the recital of an autobiographical script.
SAD is short for social anxiety disorder.
Leave it to researchers to zero down further into the mechanism behind social anxiety and tryptophan.
Another study looked at cortisol levels (HPA axis) versus another marker for the autonomic nervous system (ANS).
Their results pointed to effects in the ANS:
The most important result was that the TD group showed a significantly larger sAA response to the public speaking task as compared to the placebo group, reflecting hyperresponsivity of the ANS in this group, whereas no differences were seen in cortisol responses.
https://www.sciencedirect.com/science/article/abs/pii/S0306453009001589
This is interesting. The ANS is our system that we don't directly control.
Think of rapid heartbeat, sweaty palms, etc.
Serotonin has direct interaction with this system and "stress response".
What about Tryptophan and social anxiety directly.
A study looked at tryptophan supplementation for people with a diagnosed social anxiety disorder.
The results:
Protein-source tryptophan with carbohydrate, but not carbohydrate alone, resulted in significant improvement in an objective measure of anxiety.
https://www.ncbi.nlm.nih.gov/pubmed/18066139
You can drill down into actual specific social interaction situations.
Really specific.
For example, there's a game called Ultimatum where researchers looked at the effects of tryptophan supplementation.
The results:
Increasing serotonin through TRP supplements increased the rejection of very unfair offers.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503888/
Read that back over again….it's fascinating.
Just by adding tryptophan supplementation, people were more likely to feel emboldened to reject bad offers.
People with the supplementation were more likely to accept bad offers.
This is a function of self-confidence as impulsivity measures were not affected.
Now extrapolate that over the social anxiety or the opposite...social confidence.
See why this is so interesting?
There are lots of interesting studies on this front.
For example…
In her study, nondepressed people who took three grams of tryptophan for 12 days seemed more goal-oriented--making suggestions and placing demands on others--than did those who took a placebo. The subjects also acted less disagreeable and sarcastic.
https://www.psychologytoday.com/us/articles/200109/confidence-cuisine
This is another reflection of confidence in social settings.
Back to the beginning...early social rejection.
It turns out our brain was designed to respond to social pain the same way as physical pain.
What about inflammation (a source of physical pain?).
Let's go there now.
Tryptophan and inflammation
A study exposed participants to endotoxins to create an inflammatory response and then looked at social interaction states.
Their results:
Results revealed that participants exposed to endotoxin vs. placebo showed a greater increase over time in feelings of social disconnection.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273616/pdf/nihms350124.pdf
And the smoking gun…
Those who showed the largest increase in IL-6, one type of proinflammatory cytokine, also showed the greatest neural activity in the dACC and anterior insula in response to social exclusion.
Goodness...let's break that down.
They found that as the levels of inflammation rises, reactions to social rejection increases.
Check out CBD and neuroinflammation for anxiety to see why this is so important.
Here's the kicker.
Studies on schizophrenia (details here) are showing how early insult (due to infection, trauma, stress, etc) can create a chronic inflammatory state.
Guess what the body does in response to chronic inflammation?
It downregulates tryptophan metabolism.
The immune system can't really tell the difference from inflammation due to invading bacteria of social stress.
We have a natural system to starve out bacteria and viruses of their raw material.
Guess what it is.
Tryptophan!
The downside is we also lose serotonin creation which is why lower mood goes hand and hand with the flu.
We go into the whole reaction with our Tryptophan, inflammation, and anxiety article.
SO...some practical questions?
Can tryptophan and CBD help with social anxiety
Here's our main question (from self-interest)....can we use tryptophan and CBD to support this pathway.
We look at CBD in detail at our CBD and serotonin.
Research is showing that CBD helps to balance the serotonin pathway.
There are lots of studies like this one:
Seven days of treatment with CBD reduced mechanical allodynia, decreased anxiety-like behavior, and normalized 5-HT activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319597/?report=classic
5-HT is short for serotonin.
"Normalize" is the important word there. You'll see that or "modulate"....not boost or drop.
Remember, we don't want serotonin too high or too low.
On the other side, tryptophan supplementation supports levels within this system.
This could be a perfect 1-2 punch.
The more raw material for the pathway (tryptophan) and then the balancing of serotonin processing (CBD).
So...how do we supplement tryptophan?
Turns out there's lots of misinformation starting with Thanksgiving turkey.
What foods are high in tryptophan...does it matter?
Tryptophan is an amino acid so the main source in our food comes from animal products like meat.
In fact, there's an old tale about Thanksgiving turkey making you tired because of tryptophan.
Sorry to burst that bubble but tryptophan from food sources don't significantly boost brain levels.
It has to compete with all the other proteins to cross the blood-brain barrier.
Carbohydrates are great carriers across this barrier for tryptophan.
Ever wonder why you crave carbs when in a down mood?
Tryptophan supplementation is easy and you can get it here.
It's best without other food (or at least protein specifically).
The studies above showed a peak increase of 4-5 hours after consumption.
What about when to take it?
Does tryptophan make you sleepy
Here's the deal….tryptophan makes serotonin (as we saw above) and serotonin breaks down into melatonin.
Melatonin is key to sleep.
Studies have shown benefits for tryptophan on sleep but that doesn't somehow violate our circadian clock.
Melatonin gets released (converted) at night and not in the day.
Tryptophan does not feel like a sedative regardless of the wake cycle (like benzos or antihistamines).
At night, it will support the sleep pathway. During the day, it will support the serotonin pathway for mood and other housekeeping roles.
So...fine before sleep and fine during the day.
Interestingly, CBD has the same effect. Check out our article on whether you can take CBD in the middle of the day or CBD and sleep.
Other ways to support the tryptophan serotonin pathway
There are many ways to support serotonin function:
- Bright light (key to seasonal affective disorder in the winter)
- Exercise - naturally boosts serotonin and the end result...BDNF!!
- Meditation - see CBD and meditation for serotonin or neurogenesis
- Massage - again...social reward!
- Forest bathing - new research
- Social interaction - again, this is the social reward
- B vitamins especially folate Buy here
- Turmeric - both serotonin and dopamine - 1-2 punch! Buy here
Steroidal hormones (especially estrogen and testosteron3) directly drive serotonin function! Testosterone is turned into estrogen by aromatase in the male brain.
See estrogen and mental health.
Also, it's key to bring down inflammation so to that end:
- Fisetin- Buy Here Full review
- Berberine- Buy Here Full review
- NAC- Buy Here
The last three have powerful longevity and antioxidant effects.
Of course, CBD works within the endocannabinoid system to keep serotonin function from going to low but it gets even more intimate with tryptophan.
In fact, CBD's effect on serotonin might be via tryptophan breakdown...the prevention thereof.
The suppressive effect of both cannabinoids on mitogen-induced tryptophan degradation mediated by indoleamine-2,3-dioxygenase (IDO), suggests an additional mechanism by which antidepressive effects of cannabinoids might be linked to the serotonergic system.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033942/?report=classic
So endocannabinoids prevent tryptophan break-down.
And here's the key part for CBD:
We conclude that in particular, the non-psychotropic CBD might be useful for the treatment of mood disorders in patients with inflammatory diseases since this cannabinoid seems to be safe and its effects on activation-induced tryptophan degradation by CBD were more potent as compared to THC.
Goodness.
Make sure to check out CBD and panic attacks or CBD and social anxiety here.
They go through the dosage and type of CBD for social anxiety.
I now take a 500mg tryptophan supplement with CBD before playing basketball for confidence.
Or for any socially stressful or demanding situation.
Of course, I take 2-3 daily just to feel like the king of the jungle with my primate cousins.
The goal is to use tryptophan to "trick" our brain into thinking we're on top of the social hierarchy and let it act accordingly.
Silly primate brain.
Related Research:
Serotonin Guide
Infection and tryptophan
Supporting resilience
The self-esteem pathway
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.