In 1963, Prof. Raphael Mechoulam sent shock waves through the scientific world when he became the first scientist to isolate and eventually synthesize the psychoactive ingredients in the cannabis plant – THC, CBD and several other cannabinoids – a finding that led his laboratory to discover the endocannabinoid system in 1988 These discoveries were both fundamental to the world of cannabis-related medical research, leading many to refer to him as the “godfather” and even the “father” of cannabis research.

However, his recent research into cannabis-derived acids appears to have taken cannabis research into an entirely new phase that could finally fill the funding gap between the medical treatment potential of cannabis and the funding companies are willing to invest in its research development.

These days, Mechoulam is leading the medical team for EPM, which plans to register on the Tel Aviv Stock Exchange for the third or fourth quarter of 2021.

The Jerusalem Post took up an interview last week with EPM’s CEO, Israeli entrepreneur Reshef Swisa, who teamed up with the 50-year-old scientist to create EPM in 2017, and with its chairman, veteran UK pharmaceutical company Julian Gangolli , put together companies in 2019 – to find out what exactly cannabis acids are and what impact they could have on the global medical cannabis market.

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

Swisa said cannabis acids are an exciting avenue for new research because “while the entire industry is working on the compounds that decarboxylate after the plant dries out, we have been more interested in studying what is happening on the plant itself.”

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He said that drug companies interested in investing in a new drug must have either more effective, cheaper or fewer side effects than currently approved treatments. “It has to be better than what you have now,” he said.

He added that you also need to be able to patent your drug, and told the Post that “this may be the main reason many drug companies are not considering cannabis. They can’t get the formula for a natural molecule.” patent. “

Swisa said that while the potency of cannabis acids is higher than that of cannabinoids. “The cannabis acids are very unstable, which means that they break down into cannabinoids very easily. If you were to try to take them out of the plant or to consume them, the heat from 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 that require very specific plant growth conditions.

To circumvent these obstacles, the Mechoulam team synthesized molecules in a laboratory that replicate the structures of cannabis acids but do not easily dissolve into cannabinoids, so they can be reproduced on a large scale without relying on living plants.

“We have developed 14 different molecules so far, 8 of which are entirely novel discoveries, which means that we have a very exclusive patent on them as they are a new discovery for the scientific world,” he said. “Each of these molecules has the potential to be developed into multiple drugs, while many companies can do incredible things with just one molecule.”

As an example, he cited the famous epilepsy drug Epidiolex, which Gangolli helped launch as president of the North American division of his former company GW, after becoming the first cannabis-approved drug to be approved by the FDA in 2018.

“We had children with 40 or 50 epileptic seizures per week who this product was able to reduce to very few and even seizure-free”, said Gangolli, describing the clinical phase 3 studies of Epidiolex.

“What impressed me most about the data was the fact that these products – whether cannabinoids or acids – have a profound effect. You can’t just believe that kids have stopped having seizures. That’s real,” added Gangolli .

He mentioned the cost-effectiveness and increased effectiveness of cannabis acid synthesis, which enables the treatments derived from it to treat a “massive range of inflammatory diseases”, particularly when compared to his experience with Epidiolex.

Citing the drug aspirin – a synthesized version of salicylic acid made from the bark of the willow tree – as an example of the effects of successfully synthesizing it, he said, “If we all relied on tree aspirin, we would.” be in a very sad state at this moment. “

Another example Gangolli gave of the potential effects of synthesis was the use of cannabis as a potential detoxifying agent for disaster areas. Because of cannabis’ tendency to remove dangerous metals from the soil, the plants often absorb these metals in amounts far too high to clarify pharmaceutical health standards for medicines, forcing companies to adhere to strict regulations for growers.

When asked about the drug’s effectiveness, Swisa said that her tests for colitis showed that the cannabis acids synthesized not only far outperformed CBD treatments, but also performed similarly to the gold standard treatments currently on the market and steroids in particular Prednisone

“The result was stunning. We couldn’t believe it the first time, so we did it another time and a third time … six times because we just couldn’t believe what we were seeing,” Swisa told the Post.

The importance of their findings on anti-inflammatory drugs could be very significant indeed, given that while steroids are a powerful anti-inflammatory agent, they also have a fair share of side effects, especially a weakening of immune responses.

While nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are also widely used these days, their effectiveness does not reach steroid levels. They are also known to cause side effects, particularly those related to the gut, highlighting the potential that synthetic cannabis acids could have for gut-related inflammatory diseases like Crohn’s disease and colitis.

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

When asked what other diseases EPM found synthetic cannabis acids to be potential treatment models for, Swisa mentioned obesity, skin conditions like psoriasis and atopic dermatitis, pneumonia, nausea, depression and anxiety.

Swisa says the reason they have so many possible directions for treatment is because of the company’s many collaborations with corporations and academic institutions.

“We have research institutes working with us in Israel, Canada and the UK. We have EPM product development facilities in the UK, Sweden and Denmark, and offices in the US and Australia. I can estimate that there are more than 200 people at various locations Universities and UK operating CROs are always working on our projects. “