Father of cannabis research plans a new revolution nearly 60 years later

Father of cannabis research plans a new revolution nearly 60 years later, “The more we checked, the more we saw that we have a new potential alternative to probably two of the most horrible diseases you can find today.”

In 1963, Prof. Raphael Mechoulam sent shockwaves through the scientific world when he became the first scientist to isolate and eventually synthesize the active psychoactive ingredients in the cannabis plant – THC, CBD and several other cannabinoids – a finding which led his lab to discovering the endocannabinoid system in 1988.

These discoveries were both foundational to the world of cannabis-related medical research, leading many to nickname him the “godfather” and even the “father” of cannabis research.

Father of cannabis research plans a new revolution nearly 60 years later

His latest research on cannabis-derived acids, however, seems to have taken cannabis research into a completely new phase, one which could finally bridge the funding gap between cannabis’ medical treatment potential and the funding that companies are willing to invest in its research and development.

These days, Mechoulam leads the medical team for EPM, which plans to register in the Tel Aviv Stock Exchange toward the third or fourth quarters of 2021.

The Jerusalem Post sat down for an interview last week with EPM’s CEO, Israeli entrepreneur Reshef Swisa – who teamed up with the scientist 50 years his senior to found EPM in 2017 – and with its Chairman, veteran British pharmaceutical businessman Julian Gangolli – who joined the company in in 2019 – in order to find out what exactly cannabis acids are, and what their impact could be on the worldwide medical cannabis market.

“When you look at a cannabis field, none of the plants actually contain THC or CBD or any cannabinoids. All cannabinoids will appear on a plant only after that plant is dead,” Swisa told the Post. “You learn that there is a big difference between the compound you find on a plant when it’s alive and the compound you’ll find when it’s dead.”

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Swisa said that cannabis acids are an exciting avenue for new research, since “While the entire industry is working on the compounds that decarboxylate from the plant after it starts drying up, we were more interested in looking into what happens on the plant itself.”

He said that for pharmaceutical companies to show an interest in investing in a new drug, they need it to be either more potent, cost-effective, or have less side effects than the currently approved treatments. “It must be better than what they have now,” he said.

He added you must also be able to patent your drug, telling the Post that “that may be the main reason that a lot of pharmaceutical companies aren’t looking at cannabis. You can’t patent the formula for a natural molecule.”

Swisa said that while the potency of cannabis acids is higher than its cannabinoid counterparts, “The cannabis acids are very unstable, meaning they break apart into cannabinoids very easily. If you tried to take them from the plant or tried to consume them, the heat of your body would break them down and they would decarboxylate.”

He added that cannabis acids are also not easily reproducible, depending on complicated forms of extraction which require very specific plant-growing conditions.

In order to get around these obstacles, Swisa said Mechoulam’s team synthesized molecules in a lab which replicate the structures of the cannabis acids, but do not easily break up into cannabinoids, allowing them to be reproduced on a large scale without the need to depend on living plants.

“We’ve so far developed 14 different molecules, 8 of which are completely novel discoveries, meaning that we own a very exclusive patent on them, since they are a new discovery to the scientific world,” he said. “Each one of those molecules has the potential to be developed into several drugs, while many companies can do incredible things off even just one molecule.”

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He gave as an example the famous epilepsy drug Epidiolex, which Gangolli helped launch while he was President of the North American division of his former company, GW, after it became the first cannabis-derived drug to be approved by the FDA in 2018.

“We had children who were having 40 or 50 epileptic seizures a week that this product was able to attenuate to very few and even seizure-free,” Gangolli said, describing Epidiolex’s phase 3 clinical trials.

“What struck me the most about the data, was seeing that these products – whether they be cannabinoids or acids – exert a profound effect. You cannot just make-believe children not having seizures anymore. That’s real,” Gangolli added.

He mentioned the cost-effectiveness and increased potency of cannabis acid synthesization allows the treatments derived from it to treat a “massive range of inflammatory conditions,” especially when compared to his experience with Epidiolex.

He gave the drug aspirin – a synthesized version of salicylic acid, which is derived from the bark of the willow tree – as an example of the impact of successful synthetization, saying “If we were all reliant on aspirin coming from trees, then we would be in a very sorry state at this moment.”

Another example Gangolli gave of the potential impact of synthesization was in the use of cannabis as a potential detoxifier of disaster areas. He said that due to cannabis’ tendency to clean hazardous metals from the ground, the plants can often be found to absorb said metals in amounts much too high to clear pharmaceutical health standards for medicines, forcing companies to keep stringent regulations on growers.

When asked about the potency of the drug, Swisa said that their tests for colitis showed that not only did the synthesized cannabis acids far outperform CBD treatments, but they also performed similarly to the current gold standard treatments and steroids on the market, most notably, Prednisone

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“The finding was stunning. We couldn’t believe it the first time so we repeated it another time, and a third time… six different times, because we just couldn’t believe what we saw,” Swisa told the Post.

The significance of their findings regarding anti-inflammatory drugs could indeed be very significant, seeing as while steroids are a powerful anti-inflammatory agent, they come with their fair share of side effects as well, most notably a weakening of immune responses.

While non-steroidal anti-inflammatory drugs (NSAIDs) such as Ibuprofen are also commonly used today, their potency does not reach the levels of steroids. They are also known to bring about side-effects as well, namely bowel-related ones, thus especially emphasizing the potential that synthetic cannabis acids could have for bowel-related inflammatory diseases such as Crohn’s and colitis.

“The more we checked, the more we saw that we have a new potential alternative to probably two of the most horrible diseases you can find today. Both Crohn’s and colitis are life destroying. Right now, they are forced to choose between bad and terrible,” Swisa said.

When asked what other diseases EPM has found synthetic cannabis acids to be potential treatment models for, Swisa mentioned obesity, skin disorders such as psoriasis and atopic dermatitis, lung inflammations, nausea, depression and anxiety.

Swisa says the reason they have so many potential directions for treatments comes from the company’s many collaborations with companies and academic institutions.

“We have research institutes working with us in Israel, Canada and the UK. We have facilities developing EPM products in the UK, Sweden and Denmark, and offices in the US and Australia. I can estimate that more than 200 people in different universities and CRO’s are working on our projects at any given time.”

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