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It’s Not Your Parents’ THC – Welcome Cannabidiolic Acid Methyl Ester

Cannabidiolic Acid Methyl Ester
Written by Sarah Friedman

The ‘Father of Cannabis’, Israel’s Dr. Raphael Mechoulam, who brought us isolated THC, is back once again with a synthetic cannabinoid even stronger than THC and CBD! Welcome Cannabidiolic Acid Methyl Ester. It’s definitely not your parents’ THC.

Raphael Mechoulam was born in Bulgaria in 1930, where he lived with his Jewish family through the holocaust (his father being sent to – and surviving – a concentration camp) before emigrating to Israel in 1949. In Israel, he earned his biochemistry PhD from Weizman University, and was on his way.

In 1964, Dr. Raphael Mechoulam isolated the cannabinoid THC, or tetrahydrocannabinol. This was followed up some years later by the discovery of the endocannabinoid system, and after that the discovery of ananomide, the brain’s own version of a cannabinoid. Mechoulam was also the first to recognize the synergistic effect (or entourage effect) of the different parts of cannabis working together. By 1980 he was showing how CBD, or cannabidiol, could be used for epileptic patients to treat seizures, PTSD, and schizophrenia, as well as a plethora of other life functions.

For a scientist of his stature, Mechoulam has never received the accolades as scientists in other fields, likely because cannabis has for so long been demonized, even the medicinal use of it. Now as cannabis-based medications are becoming more popular (and more legal), the ‘Father of Cannabis’ is finally getting his due.

The new discovery

The nearly 90-year-old Mechoulam is still at it. The last few months saw the unveiling of his newest finding: cannabidiolic acid methyl ester (HU 580), which comes with its own quite brazen claims. HU 580 is a synthetic cannabinoid, which is a fully stable, acid-based molecule. Dr. Mechoulam described the following:

“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.” These acids are unstable, however, and their benefits are essentially lost. Mechoulam and his team found a way to modify these acids such that they can be stable enough for their medicinal abilities to be accessed.

Did he do it alone?

No, the new discovery came in conjunction with EPM, a global biotech company, and a company looking to bring together cannabis medicine and pharmaceuticals, for better or worse… What was EPM’s part in it? The patented compound is known as EPM 301. According to Mechoulam, “EPM developed a method to work with the original substances of cannabis.”

This was added to by EPM CEO Reshef Swisa, who stated, “We took a cannabidiol acid and we stabilized it by a simple chemical procedure, called esterification; then the compound is stable.” The final product – a now patented compound – was presented as a collaboration between Mechoulam and the US-based EPM.

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Has it been shown to work?

Once they got it stable, the team could start testing the behavior of this new synthetic cannabinoid acid, and they quickly found it to be a strong anxiety and nausea suppressor. This can be seen in the 2017-2018 release of a study by Dr. Mechoulam and his team, in which they looked into the effects of cannabidiolic acid methyl ester in rats, and discovered these anxiety and nausea reducing effects.

This was followed up by yet another study on rats, this time with Dr. Mechoulam and his team looking into the usefulness of cannabidiolic acid methyl ester on depression-like behavior. They found in the conclusion that: “These findings expand the very limited existent results, suggesting that HU-580 is a potent anxiolytic agent. Taken together with its chemical stability, HU-580 emerges as a candidate for a future antidepressant medication.”

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How is it different or better?

There are new findings coming out about the cannabis plant every day. New terpenes identified, new cannabinoids isolated, new ailments it can help with. THC and CBD – the two main cannabinoids of the cannabis plant – are looked into the most, but as Dr. Mechoulam stated, these molecules are secondary to unstable acids that come first, and that harnessing these much more powerful unstable acids could mean harnessing the yet-untouched power that comes with them. And that’s exactly what cannabidiolic acid methyl ester is, a stabilized form of one of these much more intense cannabinoid acids that is now capable of producing its effects.

As part of an April 2019 keynote speech given by Mechoulam at the ICBC International Cannabis Business Conference, Mechoulam stated: “It turns out that cannabidiol acid in the studies we have undertaken so far is more potent than cannabidiol itself. The chances are that slowly and to a certain extent, cannabidiol acid will prove to be parallel to cannabidiol oil in its activity because in many aspects, it’s much more active.”

How active within a human body, and how strong these synthetic stabilized acids end up being, will certainly be topics for upcoming research. The possibilities of what they might provide – especially as conceivably stronger forms of CBD and THC, opens a whole new avenue in the world of medicinal cannabis.

Mechoulam’s Goal

One of the things Dr. Mechoulam hopes to gain with this new compound, is an alternative treatment for people using opioids and steroids. As CBD has already been shown to be a useful treatment for chronic pain, it’s quite possible this new acid will provide even stronger benefits. Both aforementioned drug classes cause many issues and having access to a less dangerous alternative in both cases could be quite useful for those suffering from ailments that require these drugs.

According to the Forbes article, Mechoulam said, “We compare our compound not only to cannabinoids, but to the existing drugs that are applied today… 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.”

In terms of steroids, Dan Peer, the managing director of the Center for Translational Medicine and also the head of the Cancer Biology Research Center stated: “It’s an interesting molecule that potentially doesn’t have side effects… It works like a steroid. If it doesn’t have adverse effects, then you have a replacement, which is great.”

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One possible downside

One possible downside to this new finding is its immediate patenting by EPM. Granted, EPM was a part of creating the stabilized acid, but it also means that they’ll have sole rights to it. As a company openly looking to bridge the gap between pharmaceutical companies and this new medical cannabis market, it’s a little unnerving to think that they now hold the power that any pharmaceutical company has over its patented drugs…something that has always set the world of natural medicine (which cannabis belongs in) apart from the pharmaceutical world.

That a plant can’t be patented. This loophole of using a synthetic process on a plant to open the door for patenting, and then throwing that patent to a company looking to mold the medical cannabis industry into just another pharmaceutical one – well, it’s a bit sad to me. And rather see-through. It’s no secret that pharmaceutical companies have been taking a lot of heat because of the current opioid epidemic.

For them, cornering the medical cannabis market is a way to save face, and not lose revenue. But can we really trust this same market that purposefully (or at the very least with absolutely no regard) got millions of people addicted to potentially deadly medications for their own profits? Because the more ‘pharmaceutical’ this becomes, the more of that we’re likely to see.

Pharmaceutical companies tend to get a bad wrap – and rightly so. Their lack of care for the masses can be seen quite clearly in insanely and unnecessarily outrageous prices, the entrance of dangerous drugs onto the market, and the concealing of testing results that do not support their purposes. The idea of taking the cannabis market, and turning it into a pharmaceutical market, seems like an ominous sign.

On the other hand, in order to better manipulate these plants and their constituent parts to get the best product, there’s no denying that we’re not working directly with the plant anymore, but rather a processed version of it, and that this processing is necessary to get the potency and effects desired. It’s certainly a conundrum.


So how powerful is HU 580? It’s hard to say, but it certainly seems promising. After all, if we know the precursor acids to CBD and THC are technically much stronger, and if we can now access them like we couldn’t before, through new processes of stabilization, it could mean that we finally have access to the most powerful parts of the cannabis plant. And there’s no telling yet just how strong that might be, or what it can mean. The only thing for sure? This is so not your parents’ THC!

Thanks for stopping by CBD TESTERS, your hub for all things cannabis-related. Stop by regularly and make sure to subscribe to the Medical Cannabis Weekly Newsletter to keep up-to-date on all the most interesting industry topics.

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About the author

Sarah Friedman

I look stuff up and and write stuff down, in order to make sense of the world around. And I travel a lot too.