wing a strong preference for inhibiting COX 2 specifically (Takeda et al. 2008).
A second study demonstrated that both THCA and CBDA inhibited COX 1 significantly but only THCA inhibited COX 2, and by only a little over 30% (Ruhaak, L. et al 2011).
Both studies showed that the carboxylic acid forms CBDA and THCA had stronger overall COX-inhibiting activity than their de-carboxylated forms CBD and THC, however. More research is needed to clarify the role the acidic cannabinoids play in moderating inflammation and determine whether or not they may be safer alternatives for this than NSAIDs, which have well-known dose-dependent or long-term use detrimental effects on the gastrointestinal and cardiovascular systems due to their COX inhibition.
Lastly, both CBDA and THCA show in vitro activity at some of the various cation channel receptors collectively known as transient receptor potentials that play important roles in pain and inflammation signal transduction such as TRPV1 and TRPV4(the “vanilloid” type); TRPA1(the “ankyrin” type) and TRPM8 (the “melastatin” type). They can block, activate, or de-sensitize these to activation by another activator (Cascio and Pertwee 2014). These are likely additional mechanisms by which the carboxylic acid forms of the cannabinoids work independently of their de-carboxylated forms to moderate pain and inflammation both centrally and peripherally.
The carboxylic acid cannabinoids CBDA and THCA are likely to be important contributors to the relief of nausea, inflammation, and pain that humans have attributed to the cannabis plant for millennia. What makes them worth studying individually today are not only their individual roles within the entourage of effects that cannabis is so well known for, but also in their ability to relieve nausea or pain alone while bypassing the sometimes debilitating or unwanted psychoactive effects produced by cannabinoids like THC that activate the CB1 receptor.
The recent popularity of websites and electronically-published books extolling the benefits of juicing of fresh cannabis leaf or whole plants to treat a variety of ailments are likely attributable to the role that CBDA and THCA play on various biological targets as enumerated above.
CBDA and THCA can also be extracted and purified out of most any other cannabis extract (Wohlfarth et al 2011) but, short of the capabilities of sophisticated chemical separation of CBDA and THCA from all other cannabinoids in a lab, one will most easily obtain an extract with a much higher percentage of the carboxylic acid cannabinoids via cold-process extracts of the fresh plant. The resulting extract must continue to be stored in a cool, dark place (Taschwer 2015) in order to preserve its unique characteristics, and should be ingested rather than smoked if the goal of therapy includes reducing the psychoactive effects produced by THC.
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