If you pin the "feeling" of anxiety on a chemical in the body, it might be cortisol.
Cortisol is our stress hormone and it lies at the intersection of our stress response and anxiety.
If that intersection is too busy...we can have anxiety.
A little cortisol now and then is needed to keep us safe and alive (the proverbial tiger in the bush but more likely a passing bus these days!).
The problem is ongoing release of stress chemicals like cortisol on a chronic basis.
Things start to go wrong...quickly.
Let's learn everything about cortisol and how we can keep it better managed.
We'll also check out what CBD does with this pathway (very interesting).
We're going to look at these topics below:
- Quick intro to cortisol functioning as it pertains to anxiety
- Cortisol and anxiety relationship
- Cortisol and the brain for anxiety
- The endocannabinoid system and cortisol
- Can CBD lower cortisol levels for anxiety
- How much CBD to lower cortisol anxiety
- Best type of CBD to lower cortisol for anxiety
Let's get into this fascinating stress messenger.
Quick intro to cortisol functioning
Technically, cortisol is a steroid hormone in the body.
It's part of a family of chemicals called glucocorticoids.
The "gluco" is an important clue.
Basically, these chemicals help regulate glucose or sugar.
In fact, glucose and cortisol rise and fall in lock-step...just an FYI
Ever hear the term "stress eating"?? You're rarely searching for broccoli to stress eat.
Most likely something sugary or rich.
The "cort" refers to their manufacturing in the adrenal glands or adrenal cortex.
Finally, they're a type of steroid.
Steroids are interesting in the body in that they are powerful anti-inflammatories (but only for short periods of time...more on that later).
Cortisol is the heavy lifter in this class of chemicals.
There's a host of issues can result from chronic cortisol release:
- Metabolism issues and diabetes
- Weight gain and obesity
- Immune issues (such as autoimmune)
- And more
Let's look at cortisol and anxiety specifically.
What is the connection there?
Cortisol and anxiety relationship
It makes sense that our primary "stress hormone" cortisol would be tied to anxiety but where's the arrow for cause and effect?
We've covered the main pathways of anxiety at our master CBD and anxiety article.
GABA was a key player in the brain signaling since it calms activity in the brain.
It's the primary lever for anxiety that benzos use such as Xanax, Ativan, and Valium (see CBD versus benzos here).
Let's come at it from the other way.
Cortisol is excitatory (in fact, it's like a turbo boost) as is glutamate.
Glutamate is the polar opposite of GABA in the brain (gas and brake pedal) and an increase there will draw down GABA.
What does Cortisol do to Glutamate levels?
It was already known that chronic stress causes a massive release of glutamate, a molecule that acts on NMDA receptors, which are essential for synaptic plasticity and thus for memory.
The researchers went on to find that stress reduces a key molecule that actually gets to the heart of how neurons function.
The long term effect of chronic cortisol can go further into actual brain damage:
states that stress leads to damage or inhibition of neurogenesis via hypercortisolemia, decreased BDNF, or increased glutamate.
That entire article is how trauma early on can knock the cortisol and stress response system off balance by altering key brain areas later in life.
See our article on CBD and BDNF.
By the way, those areas (Amygdala, Hippocampus, etc) are the same areas you'll see all over the anxiety circuit.
More importantly, is the inhibition of neurogenesis.
We have an entire article on how to neurogenesis may help to repair key brain pathways for anxiety.
It's the key to long term change!
Speaking of brain areas, what about cortisol and the key circuit of anxiety (Amygdala, Prefrontal Cortex with oversight from the hippocampus?)
Correspondingly, stress enhances synaptic plasticity and the function of amygdala neurons, an effect quite distinct from the atrophy it induces in the hippocampus and PFC.
So cortisol (main stress messenger) makes the "fear" center stronger (amygdala) and reduces the rational counterweight (prefrontal cortex) and anxiety circuit manager (hippocampus).
What about all the "white matter" connectors between brain areas tied to anxiety?
We've covered a lot of this in our CBD and general anxiety disorder article.
The "stress hormone" cortisol is believed to create a domino effect that hardwires pathways between the hippocampus and the amygdala in a way that might create a vicious cycle by creating a brain that becomes predisposed to be in a constant state of fight-or-flight.
Remember that the brain is use it or lose it.
Pathways that are traveled more often get stronger.
Think of a trail through heavy brush.
If people stop walking on it, the trail disappears with time.
If the anxiety circuit and its players are constantly triggered, it will get more robust.
There's a great explanation of the effects chronically elevated cortisol has across a range of issues here:
Maybe most important are how CBD, Mindful Meditation, and Exercise can repair brain circuits for anxiety here.
Let's move on or we'll never get to CBD's effect on cortisol.
One more stop before then.
The endocannabinoid system and cortisol
We all have an endocannabinoid system and it's intimately tied to the stress response.
In fact, research is finding that it's the manager of our stress response actors like cortisol.
The key role of this system is balance or homeostasis in all the different transactions being made across a wide range of systems:
- Nervous system - neurotransmitters like GABA, Glutamate, Serotonin and more
- Endocrine system - hormones such as cortisol and other stress responders
- Immune system - inflammatory responses in the body and brain (key to reducing damage from cortisol and glutamate spikes)
See our article on CBD and glutamate and mental health.
Cortisol is a spike away from balance. How does the endocannabinoid system adjust for this spike?
At the heart of it!
Endocannabinoids interact at specific sites in the brain called CB1 receptors.
Researchers found a direct connection between the functioning of these receptors and our cortisol's effect on anxiety:
Deficiency of CB1 receptor signaling is associated with anhedonia, anxiety, and persistence of negative memories.
When we have acute stress (which can actually be good for us...a test, exercise, etc), the endocannabinoid system works to counter the spike in cortisol in order to bring the system back to balance.
It's chronic cortisol or traumatic stress that eventually exhausts this system:
Chronic variable stress exposure reduces endocannabinoid-CB1 receptor signaling and it is hypothesized that the resultant deficiency in endocannabinoid signaling contributes to the negative consequences of chronic stress.
This is critical.
Basically, the negatives of cortisol and stress (anxiety being one of them) are a result of our endocannabinoid system not being able to respond as well.
We see this throughout the body such as with insulin-resistant diabetes.
There's an interesting player in this whole pathway.
Anandamide (AEA) is our naturally created endocannabinoid with primary residence in the brain and nervous system.
It's called the "bliss" molecule and named after the Hindu Goddess of bliss, Anand.
We've covered it in detail as its effects are generally "anti-anxiety".
Some interesting research has come out in terms of cortisol and anxiety.
Think of anandamide as a correcting mechanism...a buffer from stress-induced spikes in cortisol.
It may be the "fuel" that runs out from chronic stress and cortisol:
Interestingly, stress induction, through the use of personally relevant stress-related imagery, has been found to result in a progressive decline in the circulating levels of AEA
Why does this matter for anxiety specifically?
For example, in both healthy and psychiatric populations, lower levels of circulating AEA have been found to correlate with higher anxiety
Goodness...does the path from chronic stress and cortisol to resulting anxiety run right through anandamide and the endocannabinoid system?
Early stress, trauma, or infection can set this whole ball in motion!
There's also the key to long term brain changes as a result of chronically elevated cortisol levels.
That's even more exciting and we'll get to it next in our CBD section.
Can CBD lower cortisol levels for anxiety
Let's get right to the question at hand before jumping downstream:
This decrease in cortisol levels was significantly attenuated after CBD (basal measurement = 10.5 +/- 4.9 micrograms/dl; 120 min after 300 mg CBD = 9.9 +/- 6.2 micrograms/dl; 120 min after 600 mg CBD = 11.6 +/- 11.6 micrograms/dl).
Basically...CBD prevented a rise in cortisol with a 300mg one-time dose.
This is not surprising given the effects of CBD on stress and anxiety here.
Newer research is really diving into CBD's effect across a range of stress pathways:
Goodness...you have some heavy hitters there.
- AEA - anandamide, our master stress response balancer
- Serotonin (5HT) - the stress response manager
- PPAR - a backup anti-stress system
- TRPV - another stress backup player
A quick note...cortisol in integral to our sleep cycle. It wakes you up and cycles with the highest levels in the morning (to wake us up), decreases at night (hopefully), with a bump around 4 am (hmm hmm...anyone else with a restroom break around then??).
Too little cortisol in the morning and too much at night is a sign of cortisol dysfunction and sleep issues.
Another study looked at this aspect of CBD's effect on cortisol:
Anxiety scores decreased within the first month in 57 patients (79.2%) and remained decreased during the study duration. Sleep scores improved within the first month in 48 patients (66.7%) but fluctuated over time.
Let's dig a little deeper.
We discussed Anandamide, our natural stress responder in the brain.
What does CBD do there?
While studying psychosis (tied to anandamide levels), researchers found the following:
cannabidiol (CBD) treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement.
In this case, it's supporting the natural system we have to mediate the effects of stress in the brain.
Remember that if left unchecked, these effects can actually change brain structure with results being future anxiety (and other issues).
That's where neurogenesis comes into play.
See our article on CBD and neuroinflammation for anxiety.
Building new pathways or repairing existing ones that have been damaged by elevated cortisol levels.
We couldn't sum it up better than researchers did here:
More recently, a study conducted with transgenic mice (GFAP-TK mice) showed that 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
Basically, they're saying the anti-anxiety (anxiolytic) effect of CBD following stress was from neurogenesis in the hippocampus.
See our article on can CBD stimulate the hippocampus
Recent research is showing that SSRI's, commonly prescribed for anxiety, may also have their effect via this mechanism.
Moreover, CB1 knockout mice displayed functional impairment of 5-HT1A and 5-HT2A/C receptor-mediated neurotransmission in the hippocampus  while a loss of antidepressant behavioral effects was described after genetic blocked of CB1 receptors .
Let's translate that because it's too important.
When researchers blocked CB1 activity (endocannabinoid site), a popular SSRI lost its effectiveness for neurogenesis and effects on anxiety and depression.
Read that again. Then go check out CBD versus SSRI's here since they're the most popular medication prescribed with a nasty list of side effects.
The net effect...
- Chronically elevated cortisol (from stress) can cause brain damage
- This damage can result in anxiety (among other things)
- CBD reduces cortisol levels, supports our stress response system (Anandamide) and facilitates brain repair via neurogenesis
- This results in a direct effect on anxiety both short and long term (see CBD and anxiety here)
We have a giant review of CBD and pathways of stress.
So...how much CBD is ideal for reducing cortisol levels and helping with anxiety?
How much CBD to lower cortisol anxiety
There are two ways to look at this.
First, the cortisol question.
Cortisol will likely be reduced in a dose-dependent manner.
See our article on how CBD affects CRF corticotropin-releasing factor and anxiety.
This means that even small amounts will have an effect...albeit a smaller one.
The general introductory or wellness amount of CBD is about 25-35 mg of CBD.
The study above with significant effects on cortisol was at 300 mg of CBD.
Anxiety itself is different.
Studies that show that the short term effects of CBD on anxiety range from 300-600 mg.
The longer-term effects (neurogenesis) peak around 300 mg and then trail off as we go higher.
For this reason, 300 mg is probably the ideal maximum amount of CBD unless immediate relief is more pressing.
Also, there's interesting research on Vitamin C and cortisol levels.
One of many studies looked at vitamin C given before public speaking and the results:
Such signs of stress as elevated levels of the stress hormone cortisol and high blood pressure were significantly greater in those who did not get the vitamin supplement. Those who got vitamin C reported that they felt less stressed when they got the vitamin.
Vitamin C is a very safe and available option to combine with CBD.
Learn more here at our how many mg of CBD for anxiety article.
Best type of CBD to lower cortisol for anxiety
We've discussed histamine release quite a bit and for good reason.
40-60% of the population has histamine issues and that number only goes up for women and when we're over 40!
This is why we focus on CBD Isolate.
All the plant material in full-spectrum is not going to be great for histamine issues..
See our article on full-spectrum CBD versus CBD isolate fro anxiety.
What's the relationship with cortisol and histamine?
Histamine levels increase especially during stress. Histamine-cortisol correlation is responsible for induction inflammation in all part of the GI tract
There's a direct tie between cortisol and histamine.
The secretion of aldosterone in response to histamine markedly increased at 1 micron and those of cortisol and corticosterone significantly increased at 1 and 10 microM, respectively.
This all makes sense since both are essentially excitatory in the brain.
Interestingly, the release of one or both uses up our brake in the brain...GABA.
Yes, the same GABA that benzos boost up for anxiety!
Learn all about CBD, histamines, and anxiety.
CBD Isolate is the cleaner approach for cortisol levels.
Again, everything we do at IndigoNaturals is based on research in order to provide the best response to CBD.
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.