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) was first 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 enhances 5-HT1A signaling and seemed to have some potential for reduction of nausea 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 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 of anticipatory 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 as ondansetron, metoclopramide, and THCA.
CBDA Could Treat Anxiety
CBDA has also been studied in models of anxiety since activation of the 5-HT1A receptor is a validated anti-anxiety mechanism. The effect of CBDA on anxiety behavior of mice was largest in 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 an anti-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 of depression.
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 term potency. 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 that CBD 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.
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.
To circumvent the stability issue, a semi-synthetic analog of CBDA called HU-580 has been developed. Not only is HU-580 quite stable, it was more potent than CBDA at enhancing 5-HT1A receptor activation, and inhibiting anxiety and signs of acute and anticipatory nausea. It also was reported to have antidepressant activity in rats.
Other Activities of CBDA
CBDA has several other activities besides activating the 5-HT1A receptor. However, none are necessarily unique:
•CBDA inhibited anandamide cellular uptake.
•CBDA acted weakly at TRPA1 and TRPM8.
•CBDA had in vivo anti-hyperalgesia and anti-inflammatory effects through TRPV1. CBDA may also synergize with low-dose THC for these effects. None of these activities are unique to CBDA.
•CBDA selectively inhibited the COX-2 enzyme with an IC50 of around 2 μM. Although this study has been frequently cited to support an anti-inflammatory effect, this isn’t particularly potent. Plus another study contradicted it, showing no significant COX-2 inhibition. Plus selective COX-2 inhibitors already exist anyways.
•CBDA reduced COX-2 expression in breast cancer cells through down-regulation of the c-fos transcription factor. It also inhibited migration of breast cancer cells through a mechanism independent of COX-2. However, other studies have shown little effect of CBDAon cancer cell growth.
We can also find some additional data in various patents. For example, patents have been filed related to CBDA and:
Clinical trials of CBDA
So far, there have been no clinical trials of CBDA (or HU-580) that I have been able to find. I would not be surprised to see some in the near future though
— Read on profofpot.com/cannabidiolic-acid-cbda/