Dr. Raphael Mechoulam Interview Part 1

About Raphael Mechoulam

Dr. Raphael Mechoulam, professor in the Department for Medicinal Chemistry and Natural Products at Hebrew University Hadassah Medical School and School of Pharmacy, Institute for Drug Research, is often referred to as the “Father of Marijuana Research.” While at the Weizmann Institute of Science in Rehovot, Mechoulam secured hashish from the head of Israel’s investigative branch of the national police for use in his studies, and in 1963 his research group determined the structure of CBD (cannabidiol) and by 1964 had isolated and synthesized THC (tetrahydrocannabinol), the main psychoactive compound of cannabis.

Initially fascinated by his realization that the active component of cannabis remained unknown while the active ingredients of cocaine and opium had been isolated a century before, Raphael Mechoulam’s research projects continue to address the chemistry of endogenous cannabinoids and synthesis of novel compounds to be tested as drugs against pain, inflammation, high blood pressure and cancer, with a grant from the US National Institutes of Health. He has collaborated with colleagues in Israel, the US, Canada, Spain, Germany, Brazil, New Zealand, Italy and Japan and consults for a pharmaceutical company.

Source: Daily Bell

Transcript:  My name is Raphael Mechoulam. I’m a professor at Hebrew University. I have been there for many years. I’m doing research on the chemistry and biology of natural products, mostly, but also some drugs. There is no drug that has no side effects. It doesn’t exist. The same is probably true for cannabis.

Now being a chemist, I was particularly interested in the individual constituents of the plant. Surprisingly, the constituents of the cannabis plant were not well known when we started work many years ago, several decades ago. The psychoactive component of cannabis was not known at that time, surprisingly, again. Because morphine had been isolated from opium about 150 years before that, cocaine about 100 years before that, and yet the active component of cannabis had never been isolated in pure form. So my colleague Anie and I went ahead doing that and we published that compound, reported the isolation of the active compound of cannabis in 1964. Elucidated its structure and a little bit later also synthisized it. So it became available for research.

Now scientists like to work with a specified compound. Not just with a mixture because it is very difficult to reproduce the results. And indeed after 1964 there was a lot of work on THC and some of the other constituents which we also isolated and elucidated as structures. And for the next 20 years there was a lot of work done on these compounds and much of the things we know about these compounds, the activity of these compounds, was done at that time. One thing was not known for almost 20 years, and that was the mechanism of THC action, surprisingly so. People thought it maybe some kind of unspecified activity. Acts on the membrane or something.

Well it turned out to be a mistake actually. Allan Howlad, a young professor, at that time, a professor of pharmacology at Saint Louis found there is a receptor which was later called Cb1, and then a person in England identified the second receptor known as Cb2. Mostly in the periphery, but then at some point it also pops up in the brain, especially in neurological diseases. So now we are sure of two receptors that are present, and THC acts on them and stimulates them, and causes the activity when needed. Now receptors are not present in the body because there is a plant outside there. They are present in the body in order to be activated by something the body produces when and where needed. So we went ahead looking for the compounds in the brain and periphery that would activate these receptors. And in 1992 and 1995, we reported the most important ones.

One of them we called anandamide. Ananda comes from the Sanskrit name supreme joy, we were happy after working so hard identifying the compound. Which has, it turns out, to have a different chemical structure from the compound in the plant. It was rather strange, I would say, because the two compounds do exactly the same. And these compounds, which were identified in the brain and periphery, are derivatives of fatty acids. And these compounds are very important because the receptors are found in large amounts, high concentrations in the brain and peripherary. These compounds are extremely important, they act in a huge number of physiological conditions they interact with other neurotransmitters, they interact in other systems as well. So they are important players in our body. So there has been a huge amount of work on these two compounds. Anandamide, an other one we isolated 2AG, and so we know a lot about the mechanism and how they do and therefore we can also learn a lot about the ability of plant cannabinoids like THC, or synthetic cannabinoids, that can act on this system. Activate it or block it or change the metabolism. So, it is quite promising.

Chances are we shall have drugs, we have minor drugs, but I think that we shall have major drugs in the future that act through this particular system.

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