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“Father of cannabis” Professor Raphael Mechoulam shares new findings at Royal Society of Medicine

The world-renowned cannabis scientist was the first to discover the endocannabinoid system

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Professor Raphael Mechoulam was the first to discover the ECS

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

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

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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 

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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.” 

READ MORE  Isle of Man gives go ahead to grow medical cannabis
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Epilepsy

CBGA may be ‘more potent’ than CBD against seizures in Dravet syndrome

Dr Lyndsey Anderson said there is more to explore when it comes to creating more treatment options for Dravet syndrome.

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Seizure: A row of test tubes containing CBGA oil with a doctors white gloved hand holding one up to the light

Scientists say they have found the ‘Mother of all cannabinoids’ which may help to reduce seizures in Dravet syndrome.

A new study on mice from the University of Sydney found that three acidic cannabinoids found in cannabis reduced seizures in Dravet syndrome, an intractable form of childhood epilepsy.

The three cannabinoids are cannabigerolic acid (CBGA), cannabidivarinic acid (CBDVA), cannabigerovarinic acid (CBGVA). All three but CBGA in particular “may contribute to the effects of cannabis-based products in childhood epilepsy” noted the researchers and were found to potentially have ‘anticonvulsant properties.”

The study marks the first time that three acidic cannabinoids were found to potentially help reduce seizures for Dravet syndrome.

Speaking with Cannabis Health News, the lead author of the study, Dr Lyndsey Anderson, said: “We found that CBGA exhibited both anticonvulsant and pro-convulsant effects. CBGA was more potent than CBD against febrile seizures in a mouse model of Dravet syndrome. We also found that a combination of CBGA and clobazam was more effective than either treatment alone. Additionally, we found that CBGA was anticonvulsant in the maximal electroshock acute seizure model, a model for generalized tonic-clonic seizures.”

She added: “CBGA did, however, present some proconvulsant effects. The frequency of spontaneous seizures in the mouse model of Dravet syndrome was increased with a high dose of CBGA. Also, CBGA was proconvulsant in the 6-Hz acute seizure model, a model of focal, psychomotor seizures.”

Although CBGA shows promise, Dr Anderson also stressed that it needs more research before it can replace CBD. She cautioned that Dravet syndrome patients may still need to proceed with caution.

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“Artisanal cannabis-based products are believed to reduce seizures in Dravet syndrome patients,” she said. “As these oils contain rare cannabinoids like CBGA, it is possible CBGA then contributes to the anticonvulsant effects of these artisanal cannabis oils. However, there were proconvulsant effects observed with CBGA, suggesting that Dravet syndrome patients may need to proceed with caution. The proconvulsant liability of CBGA would need to be addressed before it replaced CBD as an anticonvulsant.”

What is CBGA?

Sometimes referred to as ‘the mother of all cannabinoids,’ CBGA is the precursor molecule to many different cannabinioids including CBD and THC. It is thought to help some diseases such as colon cancer, metabolic disease and cardiovascular disease. It is a non-intoxicating cannabinoid much like CBD.

Dr Anderson explains that more research is needed to explain how the three cannabinoids work together.

“We don’t know how they work together yet,” she said. “We found that CBGA, CBDVA and CBGVA were all individually anticonvulsant against thermally induced seizures in the mouse model of Dravet syndrome. We did not investigate whether a combination of these three cannabinoids would result in a greater anticonvulsant effect than either cannabinoid alone. Future work will definitely explore this possibility.”  

CBGA future research

This isn’t the end of the research into CBGA for Dravet Syndrome. Dr Anderson said there is more to explore when it comes to creating more treatment options for Dravet syndrome.

 

She said: “Next on the horizon for this research is to explore whether the anticonvulsant properties of CBDVA and CBGVA translate to other seizure types including spontaneous seizures in the mouse model of Dravet syndrome. Additionally, we have extensively interrogated the anticonvulsant potential of individual cannabinoids and identified ten with anticonvulsant properties.”

READ MORE  CBD/CBG brain cancer study to 'transform' treatment

 

“We are now interested in investigating what happens when we combine these anticonvulsant properties. It remains an open possibility that greater anticonvulsant effects are achieved when the cannabinoids are administered in combination.”

The study was recently published in the British Journal of Pharmacology (DOI: 10.1111/bph.15661)

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News

Breast milk of THC-positive mothers not harmful to short-term health of infants – study

Researchers reported no differences in short-term health impacts such as breathing difficulties or feeding issues.

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Breast milk: A bottle of milk for an infant

According to a new study, the breast milk of THC-positive mothers was not found to be harmful to the short-term health of premature infants.

Researchers compared early pre-term infants who were breast-fed from mothers who consumed THC to those who were fed formula or breast milk from non-THC consuming mothers.

They reported that breast milk caused no differences in short-term health impacts such as breathing difficulties, lung development or feeding issues.

The study analysed the medical records of 763 early pre-term babies from 2014 to 2020. Researchers discovered that 17 per cent of the mothers tested positive for THC at the time of giving birth. They also examined post-natal exposure through breast milk.

Researchers found that overall the babies born to mothers who tested positive for cannabis were similarly healthy at the time of their discharge when fed their mothers breast milk in comparison to those who did not receive their mother’s breast milk.

The authors wrote in the abstract: “In our study, we found no evidence that providing [mother’s milk] MM from THC-positive mothers was detrimental to the health of this early preterm population through hospital discharge. A better understanding of longer-term perinatal outcomes associated with THC exposure both in-utero and postnatally via MM would inform appropriate interventions to improve clinical outcomes and safely encourage MM provision for early preterm infants.”

Breast milk from mothers who consume THC is often restricted by neonatal intensive care units because the effects on early preterm infants are unknown. It is thought that the active ingredient can pass through breast milk. Studies have shown that breast milk is a good way to improve pre-term baby outcomes and reduce infection risk along with intestinal issues.

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Researchers cautioned women to abstain as the long term effects are still unknown.

THC-positive breast milk

Natalie L. Davis, associate professor of paediatrics at the University of Maryland School of Medicine said: “Providing breast milk from THC-positive women to preterm infants remains controversial since long-term effects of this exposure are unknown.”

She added: “For this reason, we continue to strongly recommend that women avoid cannabis use while pregnant and while nursing their babies. Our study, however, did provide some reassuring news in terms of short-term health effects. It definitely indicates that more research is needed in this area to help provide women and doctors with further guidance.”

“Teasing out the effects of THC can be very difficult to study,” Dr Davis concluded. “We found that women who screened positive for THC were frequently late to obtain prenatal care, which can have a detrimental effect on their baby separate from cannabis use. This is important to note for future public health interventions.”

The study abstract will be presented at the virtual American Academy of Paediatrics National Conference and Exhibition.

Read more: Four ways women could benefit from CBD

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Industry

New course offers expert advice on medical cannabis from doctors and patients

The Sativa Learning course includes insight from doctors and patients

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A new online course on prescribing medical cannabis will offer a detailed insight into the industry from both clinicians and patients. Cannabis Health speaks to course creator and CEO Ryan McCreanor.

Sativa Learning and the Medical Cannabis Clinicians Society (MCCS) have partnered to offer a new course on the prescribing of medical cannabis in the UK.

It will cover a comprehensive list of topics around cannabis as a medicine such as clinical evidence for medical cannabis, the practicalities of prescribing and side effects and contraindications.

The course, which will run online only, will also offer a variety of clinical and patient stories on a select list of conditions such as chronic pain, fibromyalgia, epilepsy, paediatric epilepsy, anxiety and post-traumatic stress disorder (PTSD).

Course: An advert for Always Pure Organics

Sativa Learning has already launched a successful online CBD course covering everything from the science behind the cannabinoid to UK regulations.

Ryan got the idea following his return from Canada to his hometown of Northern Ireland where he struggled to find decent quality CBD products. He started his career as a toxicology scientist before working for the Canadian government as an educator and trainer post legalisation in 2018.

“This was a way to bring a level of legitimacy to the industry by developing an accredited expert-led cannabis course,” said Ryan.

“The idea for the platform is that we want to provide education for all avenues of the cannabis industry. The CBD industry was a good place to start as I had a good level of knowledge myself so I put together a lot of the educational content myself.”

He continued: “I wanted to bring in real experts so we partnered with Professor Barnes and Hannah Deacon. All future courses will be CPD-credited. A lot of medical professionals will have to gain a certain amount of CPD points per year so they can take our course and feel comfortable that it is managed to a high started of further learning.”

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As well as Hannah Deacon and Prof Barnes, the course also includes expert panels from Dr Dani Gordon who will speak about cannabis and oncology. Other classes will include Dr Elie Okirie speaking about epilepsy and Dr Evan Lewis on paediatric epilepsy. When it comes to the syllabus, the MCCS has put together the content for the cannabis course.

Course: The two creators of the cannabis course standing next to each other looking into the camera

Sativa Learning founder, Ryan McCreanor and Professor Mike Barnes

Ryan explained that they selected the conditions they included carefully to give a broad overview of common conditions.

He said: “We picked out 10 of the most common conditions for which cannabis is prescribed. We have fibromyalgia, chronic pain, cancer pain and women’s health issues. The doctors explain how they prescribe for that condition and have a number of patients who speak on camera about their experience.”

 

Expert-led courses

When it comes to panel discussions, courses or expert lead videos, it can often feel as if patients are forgotten. Ryan highlighted that this is a key part of the course.

“Not only do we have the doctors educating on cannabis but we have a follow-up with a patient talking about their experience,” he said.

“They discuss what life was like for them before medical cannabis, what their prescription is like and how this changed things for them.

“The industry should be all about the patients so we want to make sure that their voices are heard.”

The course will be fully online, with an option to learn as you go and break and save your progress whenever you are ready.  At the end of the course, there will be an exam that will give you a presentation upon a passing grade. The exam is part of the CPD accreditation.

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Ryan added: “Some people have blasted through our CBD course in one day where they just sit down and get through it all which can take up to six hours depending on your existing level of knowledge. This course is going to be quite a bit longer but you can do it all in one day or you could do a few hours a night for six months.”

The platform will be available for anyone who wants to learn about cannabis although Ryan explained that it may be more suited towards industry professionals.

He concluded: “There are no barriers to entry. The course is going to be available for whoever wants to learn about cannabis medicine. The language we use is heavily targeted towards the medical professionals as it is aimed at that audience to teach medical professionals about the basics of prescribing.”

Access the course here

Read more: The importance of peer to peer learning in medical cannabis education

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Cannabis Health is a journalist-led news site. Any views expressed by interviewees or commentators do not reflect our own. All content on this site is intended for educational purposes, please seek professional medical advice if you are concerned about any of the issues raised.

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