There are tried and true ways to support the endocannabinoid system such as Omega 3's, exercise, manage stress better (whatever that means) but research is actually pointing in a different direction.
No, we're not leading you to a cannabis fix-it-all because THC won't work long term.
THC builds tolerance, spikes dopamine, and can cause histamine issues.
If you're low in endocannabinoids, that's the wrong direction to go.
We'll get into that later but back to our point…
Two substances that are both very safe have a side trick in boosting endocannabinoids.
It's CBD and PEA.
We'll go into how they do this below but here are the areas we'll cover:
- A quick intro to the players of the endocannabinoid system
- Why endocannabinoid deficiency is our new modern ailment
- How CBD works to boost endocannabinoids
- How PEA works to boost endocannabinoids
- The issue with THC for endocannabinoids
- How much CBD and PEA to take to boost endocannabinoids
- What's the best CBD and PEA for endocannabinoids support
Let's get started!
A quick intro to the players of the endocannabinoid system
Without getting lost in alphabet soup, it's important to understand just what we're dealing with.
Our two primary endocannabinoids are:
- Anandamide - named after the Hindu goddess of bliss
- 2-AG - named to save you from its real name
2AG is more prevalent and thought to make up the "tone" of endocannabinoid response.
Anandamide is there when the system needs a backup to stress (call the phasic response)
Think of 2AG as the ocean level of activity while anandamide makes up the waves when needed.
By stress, we mean anything that pushes one of our key systems up or down.
These systems are about as "key" as you get:
- Nervous system - including the milieu of neurotransmitters and growth factors
- Immune system -inflammatory response and cellular birth/death cycle
- Endocrine system - hormones governing everything from reproduction to appetite
You also have enzymes that break down these two players and they're really fascinating (and pivotal) in this whole story.
We're going to focus on anandamide and its breakdown enzyme, FAAH.
Because research is showing that this is where we have can have the most impact on the system.
For example, check out the review on the woman who can't feel pain, anxiety, or depression because she's unable to make FAAH.
We just named three of the primary ills of our modern world!
In fact, one of the first targets for gene editing will be FAAH (what if we can bring it down...say...20%???) Chronic pain is gone!
Anandamide is really the linchpin to boosting endocannabinoid function and FAAH is its gatekeeper or rate-limiter.
We'll focus there since the research backs it!
Before we get into this, why even bother? Why not focus on neurotransmitters directly (serotonin-like SSIRs or GABA like benzos)?
The issue with any of these meds is that they push in one direction...up up up.
The brain panics and pushes back (actually reduces receptor number and sensitivity).
That's called tolerance and it leaves you worse off than when you started!
The endocannabinoid system is such a better target since it's tasked with "balancing" these other systems.
So...why is it so out of balance these days?
Why endocannabinoid deficiency is our new modern ailment
Pick a medication ad on TV. Anyone. I can draw a straight line from the endocannabinoid system to the underlying disease.
- Autoimmune? You bet (check out CBD and autoimmune)
- Mental health? Sure. (check out CBD and mental health)
- Allergies? Yes (check out CBD and mast cell activation)
On and on and on. Autoimmune makes up a big chunk of them.
Also, did you catch the side effects in real fast talk? Goodness.
What's the connection with the endocannabinoid system?
Our body/brain is coming in contact with countless new chemicals it was never designed to deal with.
- Drugs and Medications
PFOAs (the forever chemical...it's in your blood right now). Glyphosate (RoundUp pesticide in 90% of soy, corn, and wheat. BHT?? Oh, just a petroleum-based preservative in your cereal (instead of Vitamin E which is probably ½ a cent more expensive).
As we're finding with most health issues, it all starts in the gut!
Check out our Endocannabinoid deficiency review (which is massive) to look at the research on this.
One little side curiosity is the impact of Vitamin D deficiency (see Vitamin D review here).
Here's the skinny of endocannabinoids we need to understand.
These substances are all simple fats...lipids if you will.
Why the impact with Omega 3's? They're made out of omega 3s as are many good fats.
Guess what vitamin (a steroid really) is in charge of all things fats (absorption, transport, metabolism, etc)?
Roughly half the popular is deficient in D (up to 80% for African Americans) and that's by the measure of rickets and bendy knees (around 30 nmol/nl).
The endocrinologist wants us at 70-80!!
No wonder we're having trouble with our endocannabinoid level….it's getting pounded on the production side and exhausted by our chemical environment.
Okay...enough preaching...let's get into CBD and PEA.
How CBD works to boost endocannabinoids
First, understand the mechanism we'll use.
Anandamide is made and destroyed on demand. Countless times a second across the body and brain.
FAAH is the enzyme that does the breaking down.
It's the lever we can press on to boost endocannabinoids!
All we need is a FAAH inhibitor..something that slows down its activity.
A study looking at CBD for schizophrenia (see CBD and schizophrenia):
Biochemical studies indicate that cannabidiol may enhance endogenous anandamide signaling indirectly, by inhibiting the intracellular degradation of anandamide catalyzed by the enzyme fatty acid amide hydrolase (FAAH).
To translate (please!!!)...CBD allows more anandamide to be available by blocking FAAH!
The medical research community has been searching for synthetic FAAH inhibitors to bring to market for quite some time now.
Big Pharma can't patent CBD!
Interestingly, when they make synthetic CBD (Epeliodex, etc), the side effect profile is never as good.
This reduction in FAAH has positive effects everywhere they look.
What about autoimmune?
Genetic deletion of Fatty Acid Amide Hydrolase results in improved long-term outcome in chronic autoimmune encephalitis
So...remove the FAAH gene and the animal model for MS gets better.
What about asthma?
Preclinical studies suggest that the endocannabinoid anandamide restrains allergic airway obstruction and inflammation.
How did they do this? FAAH block.
Again, it's easier to block FAAH than to give anandamide since this chemical is powerful.
THC mimics anandamide...they both fit into the CB1 receptors lock.
THC lingers around though at much higher levels which is why you can have paranoia, anxiety, psychosis, and more.
It's about balance!
CBD shows none of those in its side effect profile up to very high doses (1-2 grams) and in fact, there's interesting research on CBD helping in these pathways (see CBD and paranoia, CBD and anxiety, CBD and psychosis).
This CB1 activity is very important for depression and anxiety since it's the key to neurogenesis (brain growth and repair).
In fact, when researchers block CB1 activity, the neurogenesis and anti-depressant effects of SSRIs go away (see CBD versus SSRIs).
Unline THC which pushes CB1 activity up up up, CBD works to support the availability of anandamide which is broken down much more quickly.
The way our system intended.
CBD has many other effects (balancing neurotransmitters, anti-inflammatory, etc) but this FAAH trick is how it supports endocannabinoids.
Let's turn to PEA now.
How PEA works to boost endocannabinoids
PEA actually is an endocannabinoid, albeit a support player.
In fact, it belongs to the same family of chemicals as anandamide.
Its full name is palmitoylethanolamide. They have the same "amide" on the back end.
OEA is another cousin.
How does PEA affect anandamide levels?
Anandamide and its entourage (PEA, OEA, etc) all work as a team with anandamide being the team leader.
FAAH is tasked with breaking them all down.
If there's an increase of PEA, FAAH is busy and unable to break down anandamide as quickly.
In this respect, PEA is a de facto FAAH inhibitor!
Studies in our endocannabinoid deficiency review show that supplementing PEA causes levels of OEA and anandamide (AEA technically) to increase as well.
Now, keep in mind that PEA (and CBD) can interact with many other pathways including PPAR, TRPV, GPR55 (interesting for anxiety) but in terms of boosting endocannabinoids….this impact on FAAH is the key level.
Interestingly, 2AG levels were also shown to increase with PEA supplementation even though it's broken down by a different enzyme (MAGL).
Speaking of GPR55:
Our results indicate that PEA, acting on GPR55, enhances GABA transmission in the striatum, and triggers a parallel synthesis of 2-AG at the postsynaptic site, that in turn acts in a retrograde manner to inhibit GABA release through the stimulation of presynaptic CB1Rs.
Just a head's up...GABA is our brain's "brake" pedal and key to sleep, anxiety, and just about every process in the brain.
The striatum is key to addiction, motivation, and mental health.
That just one brain area of many examples!
So...all the buzz these days (sorry) is on THC.
Will it boost endocannabinoids?
The issue with THC for increasing endocannabinoids
We're not anti-pot or anti-cannabis.
That being said, there's a great deal of research on THC now.
THC imitates anandamide in terms of boosting CB1 activity….almost like a substitute.
As we mentioned above, FAAH is unable to similarly break down THC so it lasts longer and at much higher levels than anandamide.
This causes an overstimulation of CB1 receptors….hence the high and other attributes.
One time won't matter but if it's done long term, the body will actually push back and reduce both the number and sensitivity of CB1 receptors.
It will "downregulate". Right down to the genes that make the receptors.
Researchers are showing it takes about 4 weeks for this system to come back after stopping (see CBD and cannabis addiction).
The net-net is this...you're actually REDUCING your natural endocannabinoids with THC and cannabis.
If the goal is to increase endocannabinoids, CBD and PEA alone will do the trick!
Most importantly, they don't build tolerance like THC. The natural system isn't downregulated.
Again, this is long term use, chronic use.
Let's turn to some practical questions.
How much CBD and PEA to take to boost endocannabinoids
Studies show that CBD's effect on neurogenesis (repairing/building brain) peaks at 300 mg/daily.
That's probably our upper limit.
There are higher doses (600-800 mg) that show in research for more serious issues like social anxiety, panic attacks, schizophrenia, withdrawals, etc.
Long term, 300 mg is a good peak since neurogenesis is such a powerful effect and speaks to healthy endocannabinoid function.
- Remember that CB1 activity (where endocannabinoids do much of their work) drives neurogenesis!
- As for PEA, the research points to 600 to 1200 mg daily.
The safety profile is so strong on PEA that we can't find side effects depend on the dose so that would point to 1200mg, at least initially.
There are no known drug interactions.
What about the type of CBD and PEA.
What's the best CBD and PEA for endocannabinoids support
Both are considered nutritional supplements so we want the best quality.
For CBD, we have basic requirements:
- Organically grown in the US at FDA registered farms
- 3rd party tested
- CO2 processed
- No THC - THC normalizes and reduces long term anandamide function
- No pesticides
- No heavy metals
- No solvents
- No bacteria
- No mold
We test our oils twice to be safe.
Then there's the question of CBD isolate versus full spectrum.
All the research is on CBD isolate...CBD by itself.
The bigger question is histamine or allergic response.
We see many people have side effects with full-spectrum that go away with CBD isolate
That's exactly what led us to isolate, to begin with.
This is going to be especially important for someone with low endocannabinoid function since histamine response and allergies are probably going to be an issue.
You can easily test CBD isolate versus full-spectrum to see what we mean.
Finally, there's the cost.
We want the lowest cost per mg of CBD. We price our 6000 mg bottles at 2-3 cents per mg before discounts up to 30%.
As for PEA, there are two brands we've tested.
- LifeExtensions has a chewable 600 mg tablet
- iHerb has a capsule at 600 mg
We've found that there's a better impact with the chewable (perhaps due to the sublingual absorption) but it's more expensive.
You can test both to see or maybe start with the chewable and then switch to the capsule one established.
In studies, it generally takes 6-8 weeks for either to really integrate into the system although most people feel effects rights way (calm for CBD and pain help with PEA).
CBD, PEA, and Vitamin D are promising tools to support our endocannabinoid system.
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.