The Healing Pathways and Properties of CBD-A

The Healing Pathways and Properties of CBDa

BY KATHLEEN BRADLEY, PA-C

CBDa, or cannabidiolic acid, is the cannabinoid precursor to the more commonly known compound cannabidiol, or CBD. CBDa is a truly remarkable cannabinoid given its ability to exert therapeutic effects at low doses. CBDa has been shown to be a potent neuroprotectant, antidepressant, anti-anxiety, antiinflammatory, and anti-nausea agent. Due to the surge in popularity of CBD, CBDa has taken a back seat; the majority of the studies use rodent models at this time, and research on CBDa is still in its infancy. However, we can still extrapolate a few potential areas where CBDa can be used therapeutically in humans. Here, we will discuss CBDa’s unique pharmacological properties, potential applications, and current research.

CBDa occurs naturally in the cannabis and hemp plant as a raw, unheated cannabinoid. When CBDa is heated or exposed to sunlight, it undergoes a

chemical process known as decarboxylation. During decarboxylation, CBDa loses the acid (a) group and becomes CBD. Some may be familiar with this process, as it is commonly used to turn THCa into THC. Although both the raw acid forms of cannabinoids as well as the decarboxylated forms have significant therapeutic benefits, CBDa has its own unique pharmacological healing properties that could potentially provide additional relief for patients.

When compared to other cannabinoids, one aspect that makes CBDa unique is its pharmacokinetics. Pharmacokinetics (“pharmaco” meaning drug and “kinetics” meaning movement in Greek) is how a drug moves through, or is processed, in the body. A substance’s pharmacokinetics describes how it is adsorbed, metabolized, distributed, and removed from the body. CBDa’s unique pharmacokinetics include: high bioavailability, quick absorption into the bloodstream, and a strong affinity for the COX-2 enzyme and 5-HT1A receptor.

CBDa has been shown to have a high bioavailability, or the amount of a substance that enters the circulation once it has been consumed. For example, a drug that goes directly into the circulation, also known as an intravenous drug, has a bioavailability of 100%. The higher a substance’s bioavailability, the smaller the amount of that substance is needed to achieve the desired effect. Smoked THC has an average of 30% bioavailability, whereas ingested THC (edibles) has a bioavailability that ranges from 4-20%. Recent computer simulation model studies have predicted that CBDa has a bioavailability of up to 90%! When compared with most other cannabinoids, CBDa is extremely bioavailable, allowing patients to use a smaller amount to achieve a therapeutic effect.

CBDa also demonstrates the unique ability to be a strong selective COX-2 inhibitor. The COX enzyme is responsible for signaling painful inflammatory responses. CBDa has been shown to inhibit the COX2 enzyme, therefore blocking pain and inflammation pathways in the body. NSAIDs (or nonsteroidal anti-inflammatory drugs), like ibuprofen, naproxen, and celecoxib, help with pain by inhibiting the COX enzyme as well. Common concerns when using most NSAIDS are gastrointestinal upset and increased occurrence of cardiovascular-related events, such as heart attack or stroke. CBDa has not been shown to cause gastrointestinal upset, but rather can aid in relieving many gastrointestinal issues. To date, no research has been done to see if CBDa has any negative cardiovascular effects associated with a COX-2 blockade. The ability of CBDa to selectively block the COX-2 enzyme could potentially prove to be a therapeutically superior anti-inflammatory when compared to traditional NSAIDs, although more research is still needed at this time.

CBDa, like CBD, is non-impairing and has been shown to have anti-anxiety and antidepressant properties. These effects can be partially attributed to activating the 5HT1A receptors, a subtype of serotonin receptors. Both CBD and CBDa activate these receptors; however, CBDa has been shown to have 100 times greater affinity for the 5HT1A receptor. In mice, it has been shown that the doses of CBDa needed to aid with anxiety are 10,000 times lower than those for CBD. It has also been demonstrated that CBDa works remarkably well in relieving anxiety in mice under conditions of high stress. Due to these factors, CBDa may offer anxiolytic and mood elevating properties at doses much smaller than CBD.

In addition to helping with mood and pain, CBDa has also been shown to be very effective at treating nausea at very low doses. Using the 5HT1A receptor, CBDa appears significantly better at preventing toxin nausea, motion-induced nausea, and anticipatory nausea (also known as psychological or conditioned nausea and vomiting) when compared to CBD. Up to one-third of chemotherapy patients experience anticipatory nausea, which can present several hours before receiving treatment, and to date no pharmaceuticals exist that significantly help relieve this kind of nausea. Sublingual, or under the tongue, administration of CBDa appears to be an amenable treatment option for nausea, due to the small dose needed and CBDa’s high bioavailability.

CBDa also has some unique properties unrelated to its pharmacokinetics that could prove to be helpful in treating patients. Unlike other cannabinoids, CBDa does not interact with the CB1 or CB2 cannabinoid receptors. CB1 receptors are located in the brain and spinal cord, and when activated are responsible for the psychoactive effects of THC. CB2 receptors are primarily associated with immune response. CBD weakens THC’s ability to bind to the CB1 receptor, therefore decreasing the psychoactive effects of THC. Given that CBDa does not interact with CB1 receptors, the psychoactive effects of THC will not be inhibited by CBDa if given concurrently.

Finally, CBDa has demonstrated the ability to be a strong neuroprotectant, potentially aiding in the treatment of neurodegenerative and neuroinflammatory diseases. In conditions such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), and Alzheimer’s, a significant amount of inflammation and damage is caused to the brain and nervous system. Peroxisome proliferator-activated receptors, or PPARs, play a role in decreasing inflamed nerve cells as well as managing the malfunctioning units within the diseased cells. CBDa has been shown to activate PPARs more effectively than CBD, again meaning smaller doses can be used by patients.

CBDa shows great promise as an anti-inflammatory, anti-nausea, anti-anxiety, and antidepressant. Its high bioavailability, rapid absorption in the bloodstream, and high affinity for 5HT1A receptors, as well as the COX-2 enzyme, make it a uniquely powerful cannabinoid at low doses. Ultimately, this could translate to huge cost savings for patients. We have only begun to scratch the surface of the myriad of therapeutic potential of CBDa, and more research is needed to elucidate the full range of healing effects that CBDa has to offer.