CBDA Vs CBD: What Are the Differences?

Cannabidiol (CBD) and cannabidiolic acid (CBDA) are both well-known and abundant chemical compounds native to the cannabis and hemp plant.

CBD, the major non-psychoactive cannabinoid in cannabis, has been well investigated for its suspected therapeutic potential, and is currently thought to be able to treat epilepsy, inflammation, anxiety disorders, and a number of other common physical and neuropsychiatric conditions.

By comparison, CBDA has attracted much less attention from the public, the scientific community, and the media, despite being the precursor to CBD formation and showing promise in early pre-clinical research. But now, a trend of raw juicing cannabis and the advertisement of combination CBD and CBDA cannabis oils has thrust CBDA back into the spotlight, leaving many wondering what exactly is the difference between the two similarly named compounds.

What is CBDA?

CBDA is the chemical precursor to CBD. In a process called thermal decarboxylation, CBDA is converted into CBD when the CBDA molecule is heated and loses its acidic carboxyl group. This decarboxylation process can either happen instantly, such as when the cannabis material is lit and smoked or vaporized, or by slow degradation over time if the plant material is left to sit at room temperature.

But before any of this can happen, CBDA first has to be formed from the mother of all cannabinoids, cannabigerolic acid (CBGA).

From here, plant enzymes unique to each cannabis strain convert CBGA into some varying combination of the three major cannabinoid precursor compounds: tetrahydrocannabinolic acid (THCA), cannabichromenic acid (CBCA), cannabidiolic acid (CBDA). 

Conversion of cannabigerolic acid (CBGA), to cannabidiolic acid (CBDA), to cannabidiol (CBD).

So, despite being abundant in raw cannabis, cannabis users are not actually exposed to much CBDA, as it’s converted from its “raw” form into CBD by most of the common consumption methods. For people who want to be consuming CBDA, this means having to use more uncommon or conventional consumption methods, such as topical creams, tinctures, and joining in on the raw cannabis juice trend.

What is CBD? 

CBD is the major non-psychoactive cannabinoid in cannabis. Research has shown that it has therapeutic potential for conditions including epilepsy, inflammation, anxiety disorders, and a number of other common physical and neuropsychiatric conditions. It is also famed for its calming effects, which has led to a recent consumer boom in CBD isolate oils and balms. 

CBDA benefits

But why would people go to such lengths to get a dose of CBDA in the first place? What does the raw CBD precursor offer that CBD itself does not?

Roger Pertwee, an emeritus professor at the University of Aberdeen, detailed CBDA's therapeutic potential to Analytical Cannabis in a recent episode of our Teach Me in 10 series. Here's what he had to say:

Potential Therapeutic Uses of Cannabinoids With Professor Roger Pertwee. CBDA discussion begins at 06:04 and ends at 08:34.

Normally, CBDA and the other acidic forms of cannabinoids are not considered to be pharmacologically active. This is because they don’t affect the body’s endocannabinoid system in the same way that their decarboxylated forms do. As a result, most research has focused on the effects of CBD and THC, rather than CBDA and THCA.

But new research is beginning to challenge this idea.

It all began in 2008, when researchers noticed that the molecular structure of CBDA closely resembled that of other common nonsteroidal anti-inflammatory drugs (NSAIDs). The team then investigated the potential of CBDA to act as an anti-inflammatory agent and found that CBDA demonstrated the same COX-2 inhibitor behavior that enables NSAIDs to tackle inflammation.

CBDA is also thought to be a powerful treatment for nausea and anxiety. A 2013 study from scientists in Guelph, Canada, found that CBDA was a thousand times more powerful than CBD in binding to a specific serotonin receptor linked to anti-nausea and anti-anxiety effects when administered alongside low-doses of the traditional anti-nausea drug for chemotherapy patients, ondansetron (OND).

CBDA benefits and medical use

Despite its demonstrated therapeutic potential, CBDA has not normally been considered as a viable clinical treatment. Naturally, it’s quite an unstable compound – as seen by its gradual decarboxylation at room temperature – and so it wasn’t considered a viable option for clinical treatment.  

But new research from Dr Raphael Mechoulam – the cannabis scientist who first synthesized THC and CBD – may have broken down that barrier. Speaking at the CannMed 2019 conference in California last month, Dr Mechoulam announced that his research team has found a way to transform the unstable CBDA into a more stable compound which retains the therapeutic potential of CBDA.

“We have taken the unstable acid molecules of the cannabis plant and synthesized them to provide a stable, consistent basis for researching new therapies across a wide range of medical needs – from central nervous system disorders to inflammation and many more,” Mechoulam said in a statement.

Mechoulam and his research team worked to stabilize the CBDA by converting it into a methyl ester derivative, known as cannabidiolic acid methyl ester, or HU-580. By testing the new compound in an animal model for depression, the researchers confirmed that compound still retains its ability to reduce anxiety-like behaviors, while being chemically stable enough to hold up as a clinical drug. 

Synthesis of cannabidiolic acid metal ester, HU-580 (right) from cannabidiolic acid, CBDA (left).

“In addition, we have provided several delivery mechanisms including tablets, topical applications and others to facilitate several approaches,” said Mechoulam. “Our work is a catalyst for the development of potential new therapies from a source long thought to have huge potential.”

The discovery was made by an international collaboration of scientists from several universities in Israel, Canada, and the United States, a topical cream manufacturer, a testing lab, and the start-up company EPM.

The latter has now opened its intellectual property portfolio to the healthcare industry for licensing partnerships, in the hopes of attracting further investment. The company hopes that the compound will begin Phase 1 FDA clinical trials within the next six to twelve months.