Have You Heard of CDBA-Methyl-Ester?

The godfather of all things cannabis, Raphael Mechoulam, has created a new, synthetic form of CBDA.

Cannabis flowers produce phytocannabinoids in their raw, unheated, forms, also referred to as acid cannabinoids, such as CBGA, THCA, CBDA.

In their acid forms, cannabinoids are metabolized in different ways by the body and don't necessarily cause the same effects as their 'active' counterparts, meaning that they are mostly non-psychoactive and chemically unstable.

Cannabidiolic acid (CBDA) was first isolated by Israeli scientist Raphael Mechoulam in 1965.

Through exposure to sufficient heat/sunlight, CBDA naturally changes into CBD by going through a chemical process called decarboxylation in which the carboxyl group (-R-COOH) is lost.

Researchers have been demonstrating the potential of CDBA as an antiemetic, relieving the symptoms of nausea, vomiting and anxiety. What is more, CBDA was also proved to be substantially more effective than CBD itself in those cases.

Fresh hemp, more than medical cannabis itself, shows a considerately amount of CBDA, but because of its chemical nature, CBDA is highly unstable, being rapidly converted to CBD.

Therefore, CDBA extraction is difficult due to stability problems, leading to low yield and making it hard to study and commercialise.

In 2019, at the CannMed conference in Pasadena, California, the 88-year-old organic chemist Raphael Mechoulam announced his latest cannabis creation: synthetically stable cannabinoid compounds, fit for clinical use – the CBDA-methyl-ester.

This is exciting and unprecedented research. We have taken the unstable 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 CNS disorders to inflammation and many more.Raphael Mechoulam, organic chemist

Mechoulam and his research team worked to stabilize the CBD-A by converting it into a methyl-ester derivative (known as cannabidiolic acid methyl ester or HU-580). This also makes the research surrounding CBDA potential therapeutic functions much easier.

By testing the new CBDA-methyl-ester in an animal model for depression, the researchers confirmed that the compound still retains its ability to reduce anxiety behaviours.

Another recent study showed that CBDA-methyl-ester is more potent than CBDA at enhancing a specific serotonin receptor activation, and inhibiting signs of acute nausea and anxiety.

In conjunction with Mechoulam's team, the CBDA-methyl ester discovery was made with the help of several universities in Israel, Canada, and the United States, a topical cream manufacturer, a testing lab, and the start-up company EPM.

"In addition, we have provided several delivery mechanisms including tablets, topical applications and others to facilitate several approaches," Raphael Mechoulam said.

"Our work is a catalyst for the development of potential new therapies from a source long thought to have huge potential," concluded Mechoulam.

The Organic Chemist Raphael Mechoulam, at the age of 88, at his lab in Hebrew University, Jerusalem.

To bring the CBDA-methyl-ester molecule further investment and bridge the gap between the pharmaceutical and cannabis industries, a US-based company and a leader in the development and supply of stable cannabinoid acid molecules, named EPM launched its intellectual property portfolio to the healthcare industry for potential licensing partnerships.

"This marks the start of a new era in medical research as EPM introduces the world's first innovative licensing platform for the use of our fully stable acid-based cannabinoid molecules," said Reshef Swisa, EPM's Chief Executive Officer, in a press statement.

"The work of our world-class research team has enabled us to be the bridge between the promise for therapeutic uses from cannabis and the ability of pharmaceutical companies to utilize stable, consistent molecules that researchers can use to potentially discover new medicines," Swisa added.

During Mechoulam's speech at Cannatech 2019, he urged the scientific community to support more medical cannabis research and lamented the research time already lost and patients that missed out on cannabis-based treatments for conditions such as epilepsy.

Did we have to wait 30 years? No, we could have helped thousands of children, and we didn't.Raphael Mechoulam, organic chemist

Dr. Mechoulam suggested that pharmaceuticals and natural remedies will co-exist in the future.

"Within the next ten, fifteen years, both cannabis plant materials and derivatives like the methyl esters [will be on the market], which is not a bad situation because patients will be able to choose whatever they believe is best for them," said Mechoulam.

The company EPM claim to be based on a desire to "help people live a better life"  and is leading the way to create and untap the potential of cannabinoids acids as new pharmaceutical treatments.

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Camila Ferezin
Camila Ferezin

Camila Ferezin is a PhD student in Cell and Molecular Biology. She holds a BA in Pharmaceutical Sciences and Biochemistry and has been working with Research and Development, both in the Academic environment and Pharma company. She is passionate about Science and loves to talk about Chemistry, Biology and Physics.