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New Compound CBDA - A Future Substitute for Opioids?

Posted by Lewis Olden on
New Compound CBDA - A Future Substitute for Opioids?

An Israeli scientist named Raphael Mechoulam has announced the development of a methodology to modify and stabilise cannabidiolic acids (“CBDA”). Cannabidiolic acids are created in the cannabis plant’s growth and have the capacity to be used on a vast scale.

The resulting semi-synthetic, stable, acid based compound could be used to supress nausea from chemotherapy and as a treatment for ailments such as inflammatory bowel disease and psoriasis. Initial research indicates that these compounds are more potent than CBD or THC and have yet to show negative side effects. There is a quiet optimism that the compounds have the capability to replace some steroids and opioids.

The solution was discovered by stabilizing the acids through esterification. This could prove to be integral to the future of the cannabinoid industry as it will pique interest from large pharmaceutical companies as the process turns out the acids in a consistent form that is patentable. EPM (the company Mechoulam partnered with to conduct his research) has said that the US Food & Drug Administration (“FDA”) has informed the company that the compound would not be treated as cannabis but would be assessed in the same manner as any normal drug in development. This allows the compound to avoid the stigma and legal limitations associated with cannabis. 

The compounds formulated from cannabidiolic acids are suggested to be far more potent than cannabinoids. Without stabilisation, research has illustrated that the acids reveal themselves in the early stages of the plant’s development but dry up as the plant matures rendering them useless. THC & CBD are secondary substances that appear later in the growth cycle of the plant.

What does the current research say on CBDA?

CBDA has been on scientists’ radars for over 10 years. In 2008 research investigated the capacity of CBDA to act as an anti-inflammatory agent by specifically studying the COX-2 inhibitor aspect of the compound. Researchers compared the molecular structures of CBDA with nonsteroidal anti-inflammatory drugs that are often prescribed to treat inflammation and found that the chemical structures are incredibly similar. Nonsteroidal anti-inflammatory drugs and CBDA are both know to inhibit COX-2 receptors. This initial study showed that CBDA is a promising potential medication to treat inflammatory related conditions.

CBDA can be used to control nausea and there is early thinking that it may also be a powerful anticonvulsive. Scientists have proven that CBDA has 100x the affinity for the 5-HT receptors compared to CBD, this is due to CBDA having a higher bioavailability meaning the body can metabolize the compound with less effort and within a shorter timeframe.

This receptor affinity may mean that CBDA could be used to treat depression. CBDA operates on the 5-HT receptors in a similar manner to serotonin reuptake inhibitor which is an antidepressant medication.

What are the potential medical benefits of CBDA on the body?

The majority of cannabinoids bind directly with either CB1 or CB2 receptors, CBDA works in a different manner. CBDA interacts with the endocannabinoid system by inhibiting the cyclooxygenase-2 (COX-2) enzyme. These enzymes are associated with inflammation after an injury or infection. By inhibiting the COX-2 enzymes, CBDA can relieve inflammation and associated pain. In a 2013 rodent study CBDA was found to affect the levels of serotonin,a chemical secreted by nerve cells to help signalling between cells. Serotonin is integral to core functions such as sleeping, eating, digestion and your emotions.

In cancer patients, chemotherapy and radiation treatment can cause the body to release excessive amounts of serotonin. This causes nausea and vomiting. While vomiting can be controlled with medication, nausea is more difficult to manage and causes the patient great distress. Many cancer patients even consider discontinuing cancer treatment due to the horrendous nausea.

CBDA has been demonstrated to affect the 5-HT serotonin producing receptors which indicates that CBDA could be used a medication for chemotherapy induced nausea and vomiting. There is still a great deal of research that needs to be undertaken before there is indisputable evidence to allow CBDA to be prescribed to patients. 

GW Pharmaceuticals currently hold a patent for CBDA with the intention of it being used to treat epilepsy. GW are revolutionaries for cannabinoid treatment of epilepsy, and they have too discovered that CBDA has an improved bioavailability. This enables a more rapid onset and faster results; it was also noted that less CBDA is required compared with CBD to achieve a successful therapeutic effect.

Could this result in a CBD substitute?

The patent that is held on the use of cannabidiolic acid is the first to prove that CBD can be substituted without major changes in efficiency. 

The compound is compared to not only cannabinoids but also to existing medications that are widely prescribed. CBDA was compared to 2 conventional drugs, the first of which was prednisone. Prednisone is a drug that is mostly used to suppress the immune system and decrease inflammation in conditions such as asthma and rheumatologic disorders. Prednisone can also be used to treat high blood calcium due to cancer and adrenal insufficiency in conjunction with other steroids. The other drug that a comparison was made against was a biological drug. It was proved that the activity of the compound created by Mechoulam was extremely similar to both drugs it was compared with.

There has been research undertaken in Japan that has identified hemp as a significant source of cannabidiolic acid.

CBD is beginning to be accepted as an alternative to addictive prescription drugs. EPM & Mechoulam’s patent on the use of cannabidiolic acid is the first instance of definitive proof that these drugs can be substituted without major alterations in their efficiency.

It is imperative that the classification and regulation of the drugs is created correctly for their medical use, this is to ensure that all unwanted side effects are avoided.

It is crucial that when taking these compounds and claiming the therapeutic benefits it is done in accordance with the regulation in order to create consistency in the language. This is because people confuse recreational use with the medicinal use and aren’t necessarily looking for specific dosing.

Further research needs to be carried but cannabidiolic acids is an area to watch and it could drive the cannabis industry as whole forward, as once cannabis companies can create patentable medications it will become of great interest to the large pharmaceutical players and governments.

What is the future of CBDA?

A significant number of unknowns remain and while the future is positive for CBDA, exactly how it will be utilised will only be discovered in time. CBDA has only been anaylsed and researched for a very short timeframe with many still not acknowledging it as a viable beneficial compound. When compared with CBD, CBDA is a lot more unstable due to the natural process of decarboxylation.

However, Dr. Mechoulam’s explanation of how his research team was able to stabilize CBDA by converting it into a methyl ester derivative named HU-580 which appears to influence the COX-2 enzyme and 5-HT receptors in a similar manner to CBDA.

There is still so much to learn about cannabidiolic acid and the potential benefits and uses for CBDA will hopefully uncovered in the forthcoming years.

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