Cannabis research pioneer hopes latest discovery is not overlooked — again

Cannabis research pioneer hopes latest discovery is not overlooked — again

By Noash Smith
Decades after Raphael Mechoulam linked CBD with treating epilepsy, his latest finding may help develop new drugs for psoriasis, arthritis and anxiety.

Raphael Mechoulam explaining steps of the process at his Hebrew University lab in Israel.Daniel Fine / EPM
Raphael Mechoulam, an Israeli organic chemist and professor of medicinal chemistry at the Hebrew University of Jerusalem, remembers the letdown after his groundbreaking discoveries surrounding the structure of the cannabis compounds CBD and THC in 1963 and 1964, followed by clinical tests with CBD published in 1980. “Not much happened,” Mechoulam said, noting that it would take more than 30 years before his clinical work on using CBD, or cannabidiol, to treat epilepsy became widely accepted. Greenwich Biosciences, which is owned by GW Pharmaceuticals, was able to develop the first cannabis-derived drug that built on Mechoulam’s research. The drug, Epidiolex, treats seizures associated with two rare forms of epilepsy and was approved by the FDA only last year. But even as his work laid the foundation for the modern cannabis industry and for understanding how cannabis interacts with the human body, a white whale eluded research: cannabis acids, which are compounds that are produced in the plant when it is alive and may be more potent than their better-known derivatives, such as CBD and THC. That changed on Monday, when Mechoulam and a group of researchers announced at a medical cannabis conference in Pasadena, California, that they have developed a process for creating synthetic, stable acids that are found within the plant, and that the synthetic acids, which include acid versions of CBD and THC, are now available for licensing to companies for drug development The discovery paves the way for drug companies to potentially develop new drugs based on the acids for a variety of health issues such as psoriasis, arthritis, anxiety and inflammatory bowel disease.

Israeli Professor Raphael Mechoulam, who is known as the "father of cannabis" for his groundbreaking work with THC and is EPM's head of research.
Raphael Mechoulam explaining the steps of the synthesis of stable CBD acid at his lab at Hebrew University in Israel. Mechoulam was the first to synthesize THC and discovered the endocannabinoid system, leading to the nickname "father of cannabis."Daniel Fine / EPM

The research is the product of a startup called EPM, in partnership with Mechoulam, six universities in Israel, the U.K. and Canada, the world’s largest topical cream company and a publicly traded laboratory company. “I think it’s a big deal,” Mechoulam, who acts as EPM’s head of research, said, comparing it to his discoveries about CBD and THC. In a 2018 British Journal of Pharmacology study, Mechoulam and his co-authors wrote that their synthetic compound, cannabidiolic acid methyl ester (called HU-580 in the paper) could be more effective than existing CBD remedies, making it “a potential medicine for treating some nausea and anxiety disorders.” Those initial clinical tests found the acids have yielded results on par, and even exceeding, existing treatments, without the side effects. The naturally occurring but unstable CBD acid (CBDA) is a thousand times more potent than CBD in binding to a particular serotonin receptor thought to be responsible for alleviating nausea and anxiety. “It’s an interesting molecule that potentially doesn’t have side effects,” said Dan Peer, managing director of the Center for Translational Medicine and head of the Cancer Biology Research Center at Tel Aviv University. “It works like a steroid. If it doesn’t have adverse effects, then you have a replacement, which is great,” Peer said, discussing testing he did with cannabis acids and inflammatory bowel disease. Ziva Cooper, research director of the UCLA Cannabis Research Initiative, said EPM’s research confirms what many in the field have long suspected about cannabis acids, but have been unable to confirm due to their instability. “Their work is quite innovative, and it definitely builds on what we know related to the potential therapeutic effects of cannabinoids,” Cooper said, adding that the compound could be particularly effective for pain control. Cooper said that while more testing will be needed to determine effectiveness and safety for humans, EPM’s results so far are “quite encouraging.” As the U.S. government plans to spend $3 million to research CBD, pharmaceutical industry veterans still urge caution, while lending some insight regarding why more drugs have not been built on cannabis compounds. “People are always joking about getting the munchies if they use marijuana,” said David Campbell, a partner at the consulting firm Oliver Wyman and advisor to EPM, who has more than two decades of experience in the pharmaceutical industry. Campbell said such anecdotal evidence is a “far cry” from being able to convince a research committee or shareholders about the efficacy of cannabis to treat a condition. “The drugs that are produced are just not potent enough,” said Peer, referring to the CBD, THC, and other nonacids.

Materials used to stabilize CBD being heated up at Raphael Mechoulam's Hebrew University lab in Israel.
Materials used to stabilize CBD being heated up at Raphael Mechoulam's Hebrew University lab in Israel.Daniel Fine / EPM

These factors, in addition to social mores, have all led to a situation where pharmaceutical companies have not been a major presence in cannabis development.

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