We have a massive review of CBD and anxiety here.
If you don't want to go that deep, let's stick to the shallow end here.
First, an introduction to the enemy!
Anxiety can be thought of at different levels:
- Brain areas not communicating correctly
- Neurotransmitters exhausted or insufficient
- Too many assaults in the form of inflammation, oxidative stress, gut imbalances, histamine, glutamate, stress, etc.
This is a hierarchy if you will. Meaning, if we can have constant stress (cortisol) as an input, it will exhaust GABA (our brain's "brake" pedal) and with enough time, this will upset the hippocampus (mood manager) and hyperactivate the amygdala (fear and emotional control) while exhausting the prefrontal cortex (rational manager of our emotional response).
- The input
- The messenger
- The brain's response over time
Goodness…we're going to need to break that down.
First, the players with anxiety:
- GABA is the "hear and now" player. Target of benzos (highly addictive with a side of tolerance)
- Serotonin - stress response buffer and manager of our secret weapon, BDNF
- Amygdala - fear response area can become too strong and overwhelm the rational player…
- Prefrontal cortex - right behind your forehead; keep our fears in check!
So, in the short term, we want to support GABA
- Long term, we want to support serotonin (manager of ALL human behavior)
- Longer term, we want to support BDNF to repair, rewire, and regrown brain connections
Stress is obvious. The others need an intro, please.
The new exciting research on mental health all centers on the immune system. Yes, Mother Nature likes to multitask!
First, the immune system can get hyperactivated. A big cause of this is trauma or infection, especially during times of brain development (even 3rd-trimester in-utero).
As a result, the brain will upregulate inflammation (immune response) and downregulate GABA and serotonin!
See the connection!
Glutamate is our brain's "gas" pedal and it can also get turbocharged as our immune system's sentinels called microglia can literally spill it out when too fired up.
Glutamate is toxic to nerves when too high and it exhausts GABA!
The pieces are coming together now.
Histamine is also excitatory and part of our immune system. It directly opposes GABA in the sleep/wake cycle. The first class of anti-anxiety meds (like hydroxyzine) were actually…anti-histamines!
Oxidative stress is just another type of inflammation…a sign that our calming and detox pathways (glutathione) are taxed.
Why bring in the gut? The gut acts as a thermostat of inflammation across the body and directly to the brain via the vagus nerve (right below your lower breastplate).
If the gut has issues, the brain has issues. It also makes a great deal of our serotonin and even GABA. The bacteria (microbiome) actually do this for us…when they're in good shape.
Great…so what does CBD isolate do with any of this?
It's EVERY one of those pathways but in a specific way that's very important.
We don't want to just push key players like GABA and serotonin in one direction or we get tolerance.
Just look at benzos, alcohol (both), and SSRIs. Add in dopamine and you're looking at addiction (benzos and alcohol).
Tolerance is the enemy because it means that our natural pathways are actually getting reduced!
CBD works like a feedback mechanism (technically called an allosteric positive modulator).
No tolerance. It supports when low!
Via serotonin, it also supports BDNF, our brain's fertilizer. We did a deep dive on how SSRIs really work and it call came down to BDNF.
For anxiety and depression, BDNF is your new best friend (you just don't know them yet).
If GABA is a calming agent right now, BDNF builds with time since we're literally building brain connections!
It kicks in around 14 days after CBD starts (more on CBD and BDNF here).
This gets to the heart of brain area connections (amygdala, prefrontal cortex, hippocampus).
Longer term healing. Check out the research on CBD and brain repair.
Then the assaults!
- Stress - CBD calms cortisol and the trigger of stress called CRF
- Inflammation - CBD calms brain inflammation including microglia hyperactivation
- Oxidative stress - CBD is a more powerful antioxidant than Vitamin E or C
- Gut issues - CBD calms gut inflammation and protects the gut barrier
- Glutamate - CBD helps balance the brain excitability balance
- Histamine - CBD calms mast cell release of histamine when excessive
Okay…this sounds too good to be true. How is this possible?
Really, the kudos go to the endocannabinoid system that we all have.
It's tasked with balancing our key systems:
- Nervous system - including neurotransmitters: GABA, glutamate, serotonin, and more
- Immune system - inflammation and cellular birth/death cycles
- Endocrine system - hormones like cortisol
CBD supports anandamide, our body's main "stress" response buffer.
We put stress in quotes because it means any push or pulls that moves a pathway out of balance.
THC, CBD's cousin, mimics anandamide (at the CB1 receptor) but it hits too hard and stays for too long…so we're back to tolerance (and the side effects with THC).
CBD slows down FAAH which eats up anandamide. More subtle so…
- No tolerance
- No addiction
- No "high"
One note on the histamine piece…
We see night and day response between CBD isolate versus full-spectrum CBD and it's likely due to histamine.
We did a deep dive on CBD isolate for anxiety here.
40-60% of the population has histamine issues and that goes up as we get older and for women (as progesterone leaves; 50% by age 40).
All the research we go through in the links above are based on CBD isolate. The histamine piece is critical for anxiety and insomnia (more on the latter here).
- A great deal of anxiety's effect is from the exhaustion of GABA (short term) and serotonin (longer term)
- This can affect the "fear signal" strength between brain areas
- Brain inflammation is a major component and can be triggered by trauma, stress, and infection
- Histamine is a little-known but very powerful pathway that drives the type of CBD to take
- Tolerance is the enemy and CBD isolate shows no issue there
A few other tools to look at with CBD isolate:
- Magnesium glycinate - supports GABA and calms stress, immune response
- NAC - supports glutathione reduces oxidative stress
- Berberine - supports gut inflammation balancing
- Medicinal mushrooms - re-balances the immune system
The future of mental health is the immune system and we can calm these pathways with CBD isolate now.
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.