CONTENTS:
Bonus: link to "The Scientist" video on the story of Professor Mechoulam's life, research and discoveries
Raphael Mechoulam - Curriculum Vitae
Raphael Mechoulam was born in Sofia, Bulgaria, in 1930 to a Jewish family. He was the son of a doctor who held the position of head of the local hospital, while his mother studied in Berlin and "enjoyed the life of a wealthy Jewish family". Raphael Mechoulam received his education at the American Grade School until anti-Semitic laws forced the family to leave their hometown. Soon after, Raphael's father was sent to a concentration camp.
During Communist Bulgaria, Raphael Mechoulam began studying chemical engineering, but was not satisfied with the direction of his education. In 1949, he and his family emigrated to Israel, where he began to study chemistry. In 1952, he received a master's degree in biochemistry from the University of Jerusalem, and six years later, after writing his doctoral thesis on the chemistry of steroids, a PhD from the Weizmann Institute. Earning his PhD was only the beginning of his scientific career. Raphael Mechoulam then did postdoctoral studies at the Rockefeller Institute in New York and became a research fellow at the Weizmann Institute. In 1965, he moved to the Hebrew University of Jerusalem, where he became a professor in 1972. In 1994, he was elected a member of the Isreal Academy of Sciences.
On 10.03.2023, Friday morning, Prof Meshulam passed away at his home at the age of 92.
Professor Mechoulam - his achievements and accomplishments:
- Member of the Israeli Academy of Sciences (1994)
- Israel Prize for Science - Chemistry (2000)
- Doctor Honoris Causa of Ohio University, USA (2001)
- Honorary member of the Israeli Society of Physiology and Pharmacology (2002)
- Doctor Honoris Causa of the Universidad Computente of Madrid, Spain (2006)
- NIDA Discovery Award (2011)
- EMET award in science - Chemistry (2012)
- Award winner Rothschild Prize in the category Chemistry and Physics (2012)
- President/President of the International Association for Cannabinoid Research (1999-2000)
- Doctor Honoris Causa of the University of Guelph, Ontario, Canada (2018)
- Discoverer of the endocannabinoid system (1992)
- Total laboratory synthesis of THC, CBD, CBG
- Head of the team of scientists who discovered anandamide and 2-AG
- In 2019, he and his research team discovered a method to stabilise cannabinoid acids including CBDa
Cannabis research
In April 2019, Dr Raphael Mechoulam gave a speech at the ICBC Cannabis International Business Conference - with Health Europa. During the speech, he explained the results of his cannabis research, highlighted the scientific developments in the field and explained in detail the effects of the compounds found in cannabis. The last few decades of research have greatly expanded knowledge of cannabis, although many challenges remain for chemists and scientists. Mechoulam has made a significant contribution to cannabis research. It was he who started the medical revolution associated with a new view of cannabis. He is best known for his discovery of tetrahydrocannabinol, one of the 113 cannabinoids in it.
The properties of cannabis have been known for thousands of years
Mechoulam began his story of studying the properties of cannabis by pointing out that in ancient Syria, cannabis was used for basically all the things it is still used for now. This was the case for several thousand years. Even Dr Russell Reynolds, Queen Victoria's physician, imported cannabis from India as an aid for her migraines. Although it was never explicitly stated that the cannabis was intended specifically for the Queen, but as she was Reynolds' only patient, it actually seemed obvious.
3 stages of cannabis research
Raphael Mechoulam has distinguished three stages into which medical marijuana research can be divided. The first is phytochemistry focusing primarily on the chemistry of the plant and the compounds it produces - mainly THC and CBD. This kind of research was an area of interest some 30 years ago. The next is research on endocannabinoids involved in many physiological processes, completed about 10 years ago.
Since then, a third phase of research has been conducted - on human physiology. There are a total of dozens of compounds involved in this process, although we currently only know about the activity of five or 10 of them. At the moment, interest is focused on cannabidiol and THC. According to the doctor, it is very likely that most of the talk in the coming years will be about endogenous cannabinoids and cannabinoids that have a similar structure. Also worthy of considerable attention is the research into the therapeutic and medical use of cannabinoid acids, which, after many years of effort, has finally been stabilised making, for example, THC. use of CBDa i.e. cannabidiol acid more accessible.
THCa and CBDa acids
Undoubtedly, the acids of greatest interest at present are THC and CBD, i.e. CBDa and THCa.
The structure of cannabidiol was described as early as 1963. It was then that the structure of the THC compound was determined and subsequently synthesised. CBD and THC are still in the spotlight, but these compounds are not natural products. What is natural are their acids. Indeed, the plant produces THC and cannabidiolic acid. Although these compounds were described and synthesised many years ago, they were never tested for a simple reason - they are highly unstable and break down very easily. Only a few articles have therefore appeared on them.
THC and CBD acids, however, began to be viewed in a different way when it was pointed out that they might be the most significant. It was therefore decided to stabilise them with a simple chemical reaction so that the activity of these compounds could then be analysed and identified. Once research on cannabidiolic acid began, it became apparent that it was more potent than cannabidiol alone.
There are also chances that cannabidiolic acid will show analogous effects to cannabidiol oil. This is important because it is more active than cannabidiol in many respects. For example - animal studies have shown that it is more stable and has a positive effect on depressive behaviour.
Human studies are obviously not possible. However, assuming that most of the results observed in animals will work analogously in a model of human behaviour, it can be assumed that cannabidiolic acid will show stronger activity than CBD alone. Studies published to date prove that it shows better efficacy in the treatment of pain and depression. According to the doctor, it is very likely that the acid will slowly start to replace natural cannabidiol. This is because it not only has a stronger effect, but additionally does not have the same side effects as THC.
Synergy effect
Another aspect that attracted the interest of chemists was the synergistic effect, also known as the ambient effect. Cannabis contains many chemical compounds that do not have any activity on their own, but when combined with THC enhance its effects. Numerous studies have shown that it is all the compounds contained in cannabis that influence the end result and the achievement of the synergistic effect (entourage effect). This introduces a number of complications and means that an analytical procedure needs to be developed for most of the compounds present in cannabis to determine how each one reacts.
Research on THC
During his talk, the doctor also focused on the compound with which his work is most associated - THC. Most people are aware that it is used in connection with pain, nausea, sleep problems, appetite or anxiety attacks. It has been approved in many countries and is a prescription drug sold as medical marijuana, for example.
However, many patients prefer the natural extract to synthetic cannabinoids, probably precisely because of the synergistic effect, and also preferring to use the oral preparation in the form of drops such as hemp oil cbd, rather than inhaling cannabinoids from smoking dried or vaporised food.
Mechoulam also suggested that it has still not been studied in depth how cannabis affects people with depression. THC has been shown to have an antidepressant effect, while there are other compounds that, at a higher dose, may show the same effect. THC is also important in reducing post-traumatic stress symptoms and improving sleep quality. Clinical studies show that small amounts of THC can help patients - while ailments will not disappear completely, they will be easier to live with.
CBD vs THC
CBD balances the effects of THC. This is important information because THC in excess is associated with an increase in psychotic symptoms, schizophrenic symptoms or the appearance of delusions. CBD calms and suppresses the excessive nervous system activity caused by excess THC.
CBD binds minimally to the receptors of the endocannabinoid system. It activates their action and influences their shape. The shape of the receptors is associated with the strength and intensity of the signals they send.
THC binds to the CB1 and CB2 receptors of the endocannabinoid system in a similar way to endogenous cannabinoids.
30 years of waiting
In his speech, Mechoulam also explained the reasons for the delay of his groundbreaking research. He began his work with epilepsy. Most of the patients using cannabis had significantly fewer seizures and only one of the people studied did not feel the positive effects of cannabidiol. After the results of the study were published, the doctor and his colleagues thought that cannabis could be used as a treatment for epilepsy, but nothing like that happened for 30 years.
It was only after this time that parents in the USA discovered that plants with high amounts of cannabidiol help in cases of epilepsy. If it had not been for 30 years of waiting, thousands of children could have been helped long ago. However, it was primarily legal issues that stood in the way. It was only when parents saw the positive effects of cannabidiol that the public started to put pressure on the US authorities. Now synthetic cannabidiol is already found in an approved epilepsy drug called Epidiolex.
Treatment of schizophrenia with cannabinoids
Dr Raphael Mechoulam continued his research, subsequently focusing on the effects of cannabis on patients suffering from schizophrenia. Together with the help of colleagues in South America, the effects of cannabis on a small group of people were studied. Research on a much larger scale was conducted in Germany. It was then discovered that CBD could be a great alternative to the already used drug Amisulpride, which is admittedly very effective, but causes side effects. This is important because many schizophrenic patients do not want to take medication precisely because of the adverse effects. The use of cannabidiol could eliminate this problem.
Anandamide and 2AG - endocannabinoids
At the end of his talk, Mechoulam decided to look at the effect of cannabidiol on the human body. It was clear that it was interacting with something, probably a receptor. So they started looking for a protein with which cannabidiol could bind. This turned out to be a receptor located in areas responsible for motor control, coordination or cognitive function, all issues affected by THC. They began to look for compounds produced by the body that could activate THC and act in parallel to it. After much research, it was possible to find two compounds that, although chemically completely different, have the same activity as THC. They were named anandamide and 2AG.
While there have been many publications on these compounds, the work has tended to be limited to theoretical considerations. Anandamide has never been administered to humans, mainly for legal reasons and despite the evidence that it could have effective medical and therapeutic applications.
Quoting from Prof. Mechoulam's interview with Discover Magazine:
"From my point of view, the human body tries to fight every disease in most cases with the help of the immune system. This is a very important system, but as we know today it does not address some diseases. So the body has other ways of trying to fight these diseases, and I believe that the endocannabinoid system is one of the main systems involved in fighting diseases. In a decade or so, we will probably be talking not only about the immune system, but also just the endocannabinoid system. It may turn out to be an additional way for the body to attack disease states." - Raphael Mechoulam, 22.11.2019 in an interview with Discover Magazine
The Scientist film - the story of Professor Mechoulam's life, research and discoveries
I encourage you to watch the film The Scientist, which tells the story of Professor Mechoulam's life, research and discoveries.
Thanks to the work and courtesy of the medycznamarihuana.co.uk team, this video is available on YouTube with Polish subtitles, and you can find it by clicking on this link: https://www.youtube.com/watch?v=tmXzi6K6y-A&t=1s
Sources:
https://www.healtheuropa.eu/dr-raphael-mechoulam-revolutionary-cannabis-research/93049/
https://www.healtheuropa.eu/raphael-mechoulam-latest-findings-93683-2/93683/
https://en.wikipedia.org/wiki/Raphael_Mechoulam
https://www.cannaconnection.com/blog/6938-dr-raphael-mechoulam-worlds-foremost-cannabis-reseacher
https://www.discovermagazine.com/health/the-father-of-cannabis-research-on-the-untapped-potential-of-marijuana-as
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