One of the world’s leading cannabis scientists has shared his latest findings – the discovery of several new compounds which could play a role in managing a wide range of global health issues.
Professor Raphael Mechoulam, is widely regarded as the ‘father of cannabis’ following his discovery of the endocannabinoid system (ECS) in the early 90s.
In a one-off event at the Royal Society of Medicine in London on Monday 11 October, the professor discussed his latest work, including the discovery of new compounds that could play a role in treating brain injury, nicotine addiction and in preventing antibiotic resistance.
The event, which was organised by Integro Clinics, saw medical professionals, scientists and industry experts share their insights on the emerging field of cannabis medicine at the well-established institution.
Prof Mechoulam, shared his findings to a captive audience, attending virtually from his office at the Hebrew University of Jerusalem, in Israel.
His research offers promising potential for the treatment of a wide range of conditions and health issues.
Professor Raphael Mechoulam was the first to discover the ECS
Depression and pain
Cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA) are found in the cannabis plant before being synthesised to produce CBD and THC and are thought to be more potent.
Prof Mechoulam and his team of researchers recently stabilised CBDA, developing the compound cannabidiolic acid methyl ester (EPM301). According to a study carried out with researchers in Canada, this was found to reduce depression and lower pain in animal models.
Prof Mechoulam explained: “The plant actually doesn’t synthesise either THC or CBD. It synthesises their precursors which are acids.
“These compounds have not been investigated very thoroughly, because they are not stable, but we were able recently to stabilise CBDA by making a methyl ester and with this we have been able to look at the activity of this acid derivative.
“This particular compound, which is present in quite large amounts in the cannabis plant, is of considerable interest.”
Brain injury
Along with anandamide, 2-Arachidonoylglycerol (2-Ag) is one of two primary endocannabinoids which bind with both the CB1 and CB2 receptors.
Researchers have now found that 2-Ag is effective in reducing head trauma following traumatic brain injury, as well as reducing vasoconstriction – the narrowing (constriction) of blood vessels in the brain.
“We saw that 2-Ag when administered to mice lowers the damage [to the brain]… the damage in the control group was 50 percent higher than those that received 2-Ag,” said Prof Mechoulam, who hopes a drug will be developed using 2-Ag as a compound against brain damage.
His team was then able to identify and isolate another “more active” compound, arachidonoyl serine (AraS).
According to Prof Mechoulam, AraS acts similarly to anandamide, but does not bind to the cannabinoid receptors and is “much more potent” in reducing the effects of vessel constriction.
Antibiotic resistance
Prof Mechoulam also revealed that AraS can encourage the activity of antibiotics, potentially providing a solution to the major impending health crisis that is increased antibiotic resistance.
“One of the major problems we have in medicine today is that many of the microbes have antibiotic resistance and if we cannot overcome this major problem, we will be back as we were in the 1930s, with microbes that we cannot attack by antibiotics,” he said.
“When microbes are attacked by an antibiotic, one of the ways they resist is by producing a biofilm. Millions of microbes get together and they form a biofilm, which is not attacked by the antibiotic.
“We found that AraS can overcome the microbial resistance of these particular microbes… AraS prevents the biofilm formation by altering the surface of the cell without actually killing the bacteria.
“This may be a very promising way of overcoming microbial resistance.”
Osteoporosis
Another newly-discovered compound known as oleoyl serine (OS), an endogenous fatty acid produced in the bones, is thought to improve bone formation, reducing and even reversing the effects of osteoporosis.
Prof Mechoulam explained: “The bones we have do not stay the way they are throughout our life, they are broken down all the time by osteoclasts, and at the same time are being rebuilt by osteoblasts. In certain diseases, for example osteoporosis, the osteoclasts work overtime and the osteoblasts cannot promote enough bone formation.”
In a study, mice with osteoporosis symptoms were given OS for 40 days, with results showing that the bones stopped breaking down and began to recover.
Prof Mechoulam and colleagues concluded that OS reduces the effects of osteoporosis, reducing the breakdown of the bone and promoting bone formation.
“We can see now that bones do not continue breaking down and as a matter of fact recover,” he said.
“Most of the drugs that we have for osteoporosis usually just [work to] stop the disease or stop the disease to a certain extent. Very few of the drugs, if any at all, cause the formation of the bone again.”
Earlier this year, a stabilised derivative of OS, H2671 was also shown to exhibit “high efficacy” in reversing the effects of osteoporosis in Prader-Willi syndrome.
Nicotine addiction
Mechoulam’s colleagues in Italy have discovered another endogenous compound, again closely related to anandamide, known as oleoyl glycine (OS).
Using a conditional place preference model [where mice or rats are given the option to go to food with or without nicotine] fellow researchers in Canada found that when mice were given OG, they did not become addicted to the nicotine in their food.
Prof Mechoulam revealed he was “disappointed” that the same model didn’t work with opioid addiction, but OG did prove effective in reducing both nicotine and opioid withdrawal symptoms.
“It turns out that withdrawal and addiction are two different types of response,” he explained.
“Today we know that OG works on nicotine addiction and does not work on opiate addiction, but it does work on nicotine and opiate withdrawal symptoms.”
The authors of the study concluded that morphine withdrawal reactions were accompanied by “suppressed endogenous levels of OG in different parts of the brain.”
Mechoulam and colleagues then stabilised this compound to develop oleoyl alanine which turned out to be “more active” for a “longer period” of time than OG.
He added: “We found that oleoyl alanine is not only more stable, but also a more potent anti-withdrawal molecule than OG, and I am under the impression that this compound should [be developed] to become a drug.”
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