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Move Over CBD, Meet EPM301


Cannabis science pioneer, Raphael Mechoulam, recently announced a new process that will stabilize powerful acidic cannabinoids. 

CBD and THC are two cannabinoids with high levels of name recognition (to put it mildly). But a newly synthesized acidic cannabinoid compound may surpass them both in potency.

Sound unlikely?

Scientists have actually known for some time that acidic cannabinoids, like CBDA and THCA, have potent properties – but they are also highly unstable. This has made them difficult to study, as well as rendering them largely useless for pharmaceutical purposes – until now.

But at 88, Professor Raphael Mechoulam, known as the father of cannabis research, has once again made cannabis history. His new discovery, cannabidiolic acid methyl ester (EPM301), is a major step in cannabinoid science. But what exactly is EPM301 – and why all the excitement?

First of all, the new substance is derived from CBDA, the acidic precursor to the cannabinoid CBD. Mechoulam explains:

“The (cannabis) plant produces a group of compounds called cannabinoid acids. The acids were not investigated until recently, not very thoroughly at least, because they are not stable; they break down.”

In fact, in its natural, unstable form, CBDA turns into CBD over time (or if it is exposed to heat). Understandably, this ever-morphing quality of CBDA has made it extremely difficult to research, and impossible to use in pharmaceutical treatments. CBD and THC, on the other hand, can be isolated, studied, and applied pharmaceutically.

According to Mechoulam, 'Cannabis and cannabinoids are not a tiny project, one compound for one disease, but a very, very wide field of research.'

In Mechoulam’s words, “The medical industry wants to have pure compounds that have been investigated, that have been thoroughly tested. So a few years ago, we decided to stabilize these acids.”

Methyl Ester EPM301 is the result – a stable, reproducible, partially synthetic form of CBDA which will open doors to research on cannabinoid acids. 

The process that Mechoulam and the team at US-based biotech firm, EPM, used is called esterification, a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product.

“This is exciting and unprecedented research,” says Mechoulam, “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.” 

Also, because the stabilization method creates predictable, consistent substances, EMP301 is patentable – which, for obvious reasons, is a very big deal to the pharmaceutical industry. 

“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, chief executive officer, EPM. 

The excitement is understandable. A patentable cannabinoid is the holy grail for cannabis pharmaceutical companies like EPM – and the process of esterification creates a substance that meets the criteria for patenting. Swisa continues:

“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.”

And what are some of the possible usages for this new compound? Already, research on EPM301 is well underway, and initial findings are promising. In a recent interview with Forbes, Mechoulam described its effects on inflammatory bowel disease (IBD):

“We compare our compound not only to cannabinoids but to the existing drugs that are applied today,” Mechoulam explained. “So, for example, in IBD we compared our compounds to two conventional products: one is the prednisone (the steroids) and one is a biological drug. And in both of them, we managed to prove that the activity of our compound is very similar to the common one.”

One crucial difference between EPM’s new substance and the standard treatment, though, is the notable lack of side effects. Mechoulam is hopeful that continued research on EPM301 will reveal a wide range of treatment possibilities:

“We have two groups of compounds today that need to have a replacement: these are steroids and opioids. We believe that cannabis carries the ability to introduce replacements to these families.”

EPM301 has a long way to travel before landing on pharmacy shelves, but Mechoulam says he is hopeful that within the next few years, we’ll have the cannabidiolic acid derivative on the market “in parallel to CBD itself.”

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