oxylation reaction provides estimates that smoking cannabis yields approximately a 30% conversion of THCA to active THC; other methods such as cooking or heated solvent extractions will yield 70-90% conversion (Dussy et al 2005).
However, it is important to note that to date there is poor correlation between the percentage of THCA to THC conversion already present in a cannabis product to be consumed and the resulting pharmacokinetics (measurements in the bloodstream) or pharmacodynamics (measurable psychoactive or psychomotor effects) in humans. For example, a small study compared the levels of THC and THC metabolites (both active and inactive) in men who consumed a fixed amount of either a) a heated cannabis sativa extract; b) and unheated cannabis sativa extract; or c) pure pharmaceutical THC (aka dronabinol or Marinol®).
The unheated extract, surprisingly, turned out to provide both the highest CBD and THC blood levels on average, suggesting that whatever CBD and THC was initially ingested from the cold extract was readily absorbed and persisted in the bloodstream the longest. The heated extract, however, provided the highest total exposure to THC activity because of the sum of THC plus active metabolite 11-hydroxy-THC measured in the bloodstream. Both extracts measured blood levels of THC on average higher than in subjects given the pure pharmaceutical THC, even though both the unheated and heated cannabis extracts were CBDA dominant strain (CBDA/THCA ratio >1) (Eichler et al 2012).
While the above study provided some interesting evidence about the fate of CBD and THC after oral consumption from either heated or unheated extracts, it did not examine the pharmacokinetics or pharmacodynamics of CBDA or THCA, though there were more of these acidic forms of the cannabinoids present and ingested in the unheated extract than the heated one (and none present in the dronabinol). Thus, important questions remain about both the unique biological effects of these acidic cannabinoids on the human body as well as their potential entourage effects either kinetically or dynamically with their better-studied de-carboxylated metabolites.
Here is some of the most compelling evidence that shapes what we know about the carboxylic acid forms to date: both THCA and CBDA independently of any other phytocannabinoid, provide significant anti-nausea and anti-vomiting effects. In rats, THCA appears to be a considerable anti-nausea and anti-vomiting compound. In a study conducted in 2013, researchers determined not only that THCA was more potent compound in this regard than THC but also that THCA apparently mediated this response via 5HT1a (aka serotonin) receptors rather than the CB1 (cannabinoid) receptors whereby THC appears to exert its own anti-nausea effects as shown in other animal models (Rock 2013).
Researchers repeated similar experiments with CBDA as well, demonstrating that CBDA reduced both toxin and motion-induced nausea and vomiting in rats, via an as-yet-to-be-determined enhancement of 5HT-1A serotonin receptor activation (Bolognini et al 2013). Unlike the THCA experiment– which showed THCA and THC exerting anti-nausea effects via wholly different receptor mechanisms–CBDA appears in vivo and in vitro to work pharmacologically more similarly to CBD (e.g. both via serotonin-receptor activation), though CBDA was shown to be more potent than CBD in its serotonin-receptor-mediated effects.
Additionally, CBDA and THCA have been shown in vitro to block, in varying degrees, both cyclooxygenase (COX) enzymes 1 and 2, which are each distinct mediators of inflammation and pain secondary to inflammation. Non-steroidal anti-inflammatory (NSAID) drugs such as acetylsalicylic acid (aspirin), ibuprofen, naproxen, indomethacin, and diclofenac all work via COX 1 and 2 inhibition, and, like CBDA and THCA, contain a carboxylic acid group in their structures that suggests this part of the molecule is integral to the way they work.
In one assay, CBDA but not THCA significantly inhibited both COX 1 and 2-mediated oxidation activity, with the CBDA sho