Updated Research on CBDA versus CBD
We've dived into exactly how CBD works and you can find 1 million-plus words on CBD research.
We also went deep into the differences between CBD and THC (almost opposite and opposing effects in the body and brain).
There's new interest (and marketing) around CBDA these days and like with all things, we want to go deep into the research.
Is there a benefit to CBDA over CBD?
Let's find out!
The key topics we'll cover are as follows:
- The relationship between CBD and CBDA
- Research on CBD and CBDA
- CBD versus CBDA and serotonin (mood)
- CBD versus CBDA and COX2 (pain)
- Side effect profiles on CBD versus CBDA
- Does CBDA break down?
Let's get started!
The relationship between CBD and CBDA
In danger of drowning in 3-4 letter words, let's first understand what CBD and CBDA are.
They both come from the hemp or cannabis plant (a legal distinction really).
There's a mother of all cannabinoids called CBGA.
Interestingly, there's a long lineage with CBGA back to berberine (see berberine and gut health) which we've covered in detail due to its powerful health effects.
CBGA then breaks down into THCA and CBDA.
Essentially, the version of THC and CBD with an acid attached.
When heat is added, the acid is shed and you have THC and CBD.
Essentially, CBDA is the precursor to CBD after a bit of heat (called carboxylation).
Applying fire (as in smoking) to the plant will quickly convert the THCA to THC.
CBD sold in the US is generally heated to drive this transformation directly.
So...the big question is...how are they different?
Let's go to the research!
Research on CBD and CBDA
First, this isn't a fair comparison.
There are over 3000 studies on CBD and just over 100 for CBDA.
This is a major issue for us since we focus so heavily on research.
Here's what we do know and we'll walk through each item:
- CBDA gets converted into CBD within the body (primarily by the liver)
- There are some shared pathways between the two (maybe more)
- CBDA is not stable as it breaks down with heat, light, and air to CBD
- CBDA's effect (if intact) may have bigger or smaller effects on certain pathways (which is good and bad)
Let's look at these key differences one by one.
CBDA gets converted into CBD within the body (primarily by the liver)
CBDA basically manifests itself in the body as CBD. Perhaps a high level of CBD:
Conversely, literature has shown that providing oral CBDA rather than CBD, actually results in a 3-fold higher Cmax of CBD in the bloodstream of people
Cmax is a measure of blood level for various substances.
So, CBDA can convert to a higher level of CBD in the blood.
That's a good thing. Assuming that the CBDA is stable (more on that later).
Let's turn to the pathways!
There are some shared pathways between the two (maybe more)
We've established the key pathways that CBD works in at our how exactly does CBD works in and logically, CBDA works along the same lines since it essentially gets turned into CBD!
Of course, we have lots of research on CBD directly with these pathways, and here's a good overview here:
As for, CBDA, the most prominent research is on:
- Serotonin function (see CBD and serotonin)
- COX2 (pain pathway tied to NSAIDs) - see CBD versus NSAIDs.
- CBDA and inflammatory pathways
Again, if we had the research to support it, we would likely find a fair amount of crossover as CBDA is converted.
We'll touch on any differences between CBD and CBDA from research on these pathways below.
Let's turn to the biggest difference.
CBDA is not stable as it breaks down with heat, light, and air to CBD
CBD isolate (which we deal with) is very stable.
It's similar to sugar or salt in that it can remain active for months without little change.
This isn't true for full-spectrum CBD due to the plant material included but CBD isolate is basically an extract that can exist for quite some time.
This is probably the biggest difference between CBD and CBDA in terms of health benefits.
CBDA WANTS to break down (to CBD).
Heat, light, and air all break it down.
That's the main reason you see CBD bottles for sale and not CBDA.
Every time you open the bottle, it would lose some effect. Room temperature alone can break down CBDA.
There is work by the Israeli Godfather of CBD research to make a synthetic version of CBDA called HU-580 which can remain more stable.
The issue is that any time we've come across a synthetic version of a natural substance, it never works the same way.
- Hydrogenated oils versus natural oils
- Fake sugars versus sugar
- Progestins versus progesterone
There's even a synthetic version of CBD called Epeliodex for seizures and the side effect profile is much worse than just plain CBD.
The price tag is much bigger as well but you can't "patent" natural CBD as a pharmaceutical.
This is very similar to the $25K synthetic version of allopregnanolone (pregnenolone, its booster, costs $10) for postpartum depression.
This work on HU-580 gets around the stability problem that CBDA has but we already know the side effect profile of CBD (which is very strong after two decades of research up to 1500 mg doses).
Let's look at one other difference.
CBDA's effect (if intact) may have bigger effects on certain pathways (which is good and bad)
CBDA may have stronger effects than CBD for certain pathways such as serotonin.
This makes sense as we saw above that CBDA is much more bioavailable in the body as it converts to CBD.
Basically, more CBD is getting into the system!
You can make up for this in two ways with CBD:
- Take after a fatty meal
- Hold under your tongue up to 60 seconds
These two steps can boost CBD availability by 4-5 times!
The more prominent effects on pathways such as serotonin (assuming we have CBDA that hasn't degraded) are both good and bad.
On one hand, you will see more of an effect such as anti-nausea (which is controlled by serotonin).
The issue is that serotonin is a very sensitive pathway that relies on balance.
- Too little and you have depression, anxiety, and other issues.
- Too much and you have agitation, insomnia, and it's even dangerous (serotonin syndrome).
Balance is the key!
CBD has been shown to "rescue" serotonin function when it's low (see CBD and serotonin).
SSRIs actually boost serotonin but there's a push back effect with long-term use where our natural serotonin pathway is suppressed.
We don't have research on whether CBDA would cause this while we do have research on CBD itself (no tolerance or addiction or withdrawal effects).
There are other pathways where CBDA is less effective.
Let's zero in on the two big studies that highlight these differences with CBDA.
CBD versus CBDA and serotonin (gut and mood)
Serotonin is a powerful player in both the gut and brain.
One of the prominent studies looked at CBDA for the gut in terms of serotonin which governs nausea (and a host of GI functions).
This is the case of CBDA having a stronger effect in the gut:
CBD60 and its precursor CBDA,41 also interfere with acute nausea-induced conditioned gaping in rats without impairing the locomotor activity. CBDA was 1000 times more potent than CBD in reducing acute nausea.
Keep in mind that the dosages were 1000 times lower for the CBDA (micro versus milli).
The researchers pinpointed this effect on serotonin function specifically.
Again, the issue is that CBDA starts to break down pretty readily which doesn't figure into the study above.
As the original researchers for CBD put it:
CBDA is naturally occurring, but very unstable and is much stronger than CBD with no side effects
There's quite a bit of study on CBD and mental health tied to serotonin as well!
We don't have those studies on CBDA yet.
Initial evidence is pointing to CBD being slower but longer-lasting while CBDA is faster but shorter-lasting.
Again, this assumes we can keep CBDA stable in a non-synthetic version.
CBD versus CBDA and COX2 (pain)
The other key area of study with CBDA deals with pain.
We've covered the COX2 pathway with our CBD versus Advil or CBD versus Tylenol reviews.
The first useful evidence dates back to just over a decade ago, when CBDA was found as a selective cyclooxygenase-2 inhibitory agent
It also affects another key pain and inflammatory pathway called TRPV but with LESS effect than CBD:
However, CBDA seems to exert these effects with significantly less potency than CBD.
So...CBDA (if it could be stable) is stronger for COX2 and serotonin in the gut but less effective for inflammation than CBD.
One caveat...we need further research to make sure that effects are not too strong on serotonin and COX2.
"Inhibition" of COX2 is not great as we see from the side effects of NSAIDs.
CBD works as a feedback mechanism, technically called an allosteric negative modulator.
It's important not to go too high or low with key pathways like serotonin and COX2 but we don't have the research there yet on CBDA (including dosage).
Let's look at info on side effects.
Side effect profiles on CBD versus CBDA
The research is pretty thin on CBDA as opposed to CBD with full profiles (see CBD safety).
Although CBDA appears to just be an unstable but condensed version of CBD (where our liver "unpacks" it), there are clearly some differences such as the TRPV effect above.
We would expect more effect across the board if CBDA was just a condensed or readily available version of CBD but having LESS effect on TRPV goes against this.
We don't see sedation or other more obvious effects from CBDA or CBD.
Again, we need more research.
To date, we have studies on mice and cells.
The dosage piece is important since it's trickier to deal in micrograms.
As it is, a high amount of CBD is our 6000 mg bottle. The equivalent would be about 6 micrograms of CBDA.
These small levels make using CBDA functionally difficult.
It's like trying to eat 1000 atoms of a piece of bread.
Finally, the only question that really matters in terms of getting any health benefits from either CBDA or CBD.
Does CBDA break down?
Yes, and this is THE issue.
Heat, light, and air will break down CBDA readily.
In fact, it wants to shed its acid piece (the "A") and become CBD.
This doesn't mean that your 1 microgram of CBDA turns into 1000 mg of CBD.
We started at a much lower total amount and so the CBD at the end will be minuscule.
Even with room temperature, CBDA will readily convert to CBD.
THCA is the same thing for THC. In fact, THCA is not psychoactive until it's turned into THC by the liver.
We love the potential of CBDA if only there was a way to make it more stable without going synthetic which never seems to work that well in the body (judging by the last 100 years).
We'll keep our eyes out for a way to readily take advantage of CBDA if anything changes on that front.
Until then, it's probably just really good marketing of the "new kid on the block".
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.