CBDA is much more potent at the 5-HT1Areceptor than CBD. This could mean improved therapy for nausea/vomiting and anxiety, but clinical trials are lacking.
Cannabidiolic acid (CBDA) wasfirst isolated in the 50’s. Then (like most other minor cannabinoids), not a whole lot happened with it for several decades. Even as CBD research started to take off in the 90’s and 2000’s, CBDA lagged behind.
Finally in the last few years, research on CBDA has started to pick up. In many cases, CBDA works in the same way as CBD, but has several important advantages. Although no clinical trials have started yet, I wouldn’t be surprised to see some in the future.
CBDA Activates the Serotonin 5-HT1AReceptor
In 2012, it was reported that CBDA enhances5-HT1Asignaling and seemed to have some potential forreduction ofnausea and vomitingthrough this mechanism. At first glance, this wasn’t too exciting since CBD also shares this mechanism. But two things separated CBDA from CBD:
CBDA demonstrated about100-fold greater affinityfor the 5-HT1Areceptor than CBD, allowing much lower doses
CBD has abell-shaped dose-response curvefor both nausea and anxiety. If the dose gets too high, then it loses its effect.
CBDA Could Treat Nausea & Vomiting
CBDA has since been studied a whole lot more in animal models. It suppressed acute nausea and vomiting when combined with low doses of THC. Similar reductions in nausea were seen with intra-gastric dosing (the equivalent of oral dosing in humans).
Promising results were also seen in animal models ofanticipatory nausea, which tends to occur in cancer patients undergoing chemotherapy. CBDA alone had an effect at doses as low as 0.5 ug/kg and as low as 0.1 ug/kg when combined with other anti-nausea medications, such asondansetron,metoclopramide, andTHCA.
CBDA Could Treat Anxiety
CBDA has also been studied in models ofanxietysince activation of the 5-HT1Areceptor is a validated anti-anxiety mechanism. The effect of CBDA on anxiety behavior of mice was largestin the presence of a stressor. CBDA did little to unstressed mice, but had a very potent anti-anxiety effect (at 0.1 ug/kg) when mice were stressed.
For comparison, CBD generally has ananti-anxiety effect in mice starting at around 1 mg/kg (although it highly depends on the study design). CBDA is is showing an effect at a dose that is 10,000 times lower!
CBDA has also shown activity in rodent models ofdepression.
Advantages of Increased CBDA Potency
It is fair to ask what is the advantage of CBDA having better potency vs. CBD? Many people misunderstand the pharmacological termpotency. Having higher potency does not mean that it necessarily works better, but rather that it exerts its effect at a lower dose.
So why would it matter that you could give CBDA at a lower dose if it is doing the same thing as CBD? Clinical studies have shown thatCBD has an acute anti-anxiety effect (i.e. after a single dose), but the dose needs to be relatively high – around 300 mg. If results from animals translate to humans, we could potentially be using low milligram (or even sub-milligram) doses of CBDA. Obviously the appropriate dose would need to be confirmed in clinical trials, but let’s assume that CBDA works at 1 mg.
This would potentially be much less expensive (300 mg doses of CBD are cost prohibitive for most people)
Oral absorption would potentially be more rapid and consistent (CBD quickly reaches solubility limitations in gastric fluid that can slow absorption)
Lower doses makes it more amenable to alternative routes of administration (e.g. sublingual). This may be especially important for nausea/vomiting.
Stabilized CBDA Derivative
Everything with CBDA probably sounds great so far, but it does have one large disadvantage. CBDA is not particularly stable and can easily be decarboxylated to CBD. This is rapidly accelerated if exposed to heat.