HU-580 – Cannabidiolic Acid Methyl Ester

by | Jan 18, 2021

Written by Deborah Agboola

The journey of cannabis has been long and bumpy, albeit progressive. Often, it had looked like the end for the cannabis industry. However, like a Phoenix rising from its ashes, it continually finds a way to pull through, stirring up twice as much interest with its many conquests. 

As it should, this resilience is finally paying off, considering the many pleasant reforms coming through and the awakening discoveries in the industry. This, of course, strengthens its foundation of purpose and the desires of humans to benefit from nature’s gift.

While some scientists are conducting further tests on the plant and exploring other applications, others are digging-in on already popular uses to further augment their efficiency. 

The latter is the case of Dr. Raphael Mechoulam, commonly known as “the father of cannabis research” and the Cannabidiolic acid Methyl ester.


For a scientist almost 90-years old, Mechoulam is surprisingly still at it. Just recently, the scientist who had begun the foundation of cannabis research by discovering the endocannabinoid system released new findings: the cannabidiolic acid methyl ester (HU580).

The introduction of this new proprietary compound sparked new waves of enthusiasm for the future of medical cannabis. Working in collaboration with EPM—a global biotech company looking to bridge the gap between cannabis medicine and pharmaceuticals, Mechoulam released a means of harnessing the benefits of natural cannabidiolic acid (CBD) in a more delivery-efficient way.

“Originally, there is an acid that appears in the plant, and those acids are these mysterious worlds of compounds that are much more potent than cannabinoids,” Dr. Mechoulam had described. This statement was the basis of his research. These acids, considered the most potent of all cannabinoids, were so unstable that their benefits were often lost before utilizing them. So there began his work: “find a way to modify them, and have them stable enough to exploit their therapeutic abilities.” 

Cannabidiolic acid (CBDA) is well known to be a prime component of the plant and a precursor molecule of CBD (cannabidiol). So, there is more data on the potentials of cannabidiol than there is on CBDA. However, the limited amount of information obtained from the few successes in exploring CBDA suggests a wide array of possibilities in the elusive phytocannabinoid. 

The instability of CBDA sadly remained an inhibition to developing it as medicine. To use Biblical parlance: we could see the Promised Land but could not think of a possible way of getting there. 

This thankfully did not discourage Mechoulam and his team as they forged on in the search for an alternative path: a more stable analog with a similar biological profile.

Eventually, the team of scientists decided to compare CBDA with its methyl ester—since the decarboxylation of phenolic acids proceeds through the carboxyl anion of the acid. This action proffered a breakthrough because they discovered that the compound’s methyl ester analog (EPM 301/HU-580), while presenting even more potent beneficial expressions of its non-methyl ester form, remained stable and unchanged, under preservation at 4®c for 21 days.

We are looking at next-gen medicine or perhaps current-gen pharma drugs with this discovery. Quoting Dr. Mechoulam, “We urgently need new drugs for various diseases, and some of the available drugs are quite good but ultimately cause side effects” – referring to commonly used circulation drugs, which are mostly semi-synthetic at best. He added: “Two groups of compounds must be replaced today: steroids and opioids. We believe that cannabis can introduce substitutes to these families.”

In support of his last statement, the EPM patent has shown that the drugs are adequately substitutable and without considerable changes to their effectiveness. By comparing the compound, prednisone (a steroid), and a biological drug, the team of scientists could demonstrate that the EPM 301’s activities were very similar to the drugs used in the comparison. 

After stabilizing the cannabidiol acid and producing EPM 301, the team began studying its activities. In the process, they confirmed its potency as an anxiety and nausea suppressant— a breakthrough in conditions synonymous with chemotherapy. Also, like CBDA, the compound is effective in reducing depression.

The discovery of this compound brings a whole new outlook to the intuition of medical cannabis research. And speaking at the conference where he announced his discovery (CannMed 2019), Mechoulam confirmed this in a statement, “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.” 

Also, Professor Mechoulam is currently leading cannabis cancer research with $2 million in funding.


Speaking at the International Cannabis Business Conference in April 2019, Mechoulam said: “It has been shown that cannabidiolic acid has been more effective than cannabidiol in the studies conducted to date. There is a possibility that cannabidiolic acid will slowly and up to some extent have its activity parallel to cannabidiol oil because it is much more active in many ways.”

Armed with this information, the next researchers will focus on the human body's activity and the strength of this synthetically stabilized acid. However, the possibility of what HU-580 has to offer opens a whole new path in the world of medical cannabis.