Compound interest Meet the scientist who mapped marijuana

Israeli chemist Raphael Mechoulam is known to many as "the grandfather of cannabis research."

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Hey there, time traveller!
This article was published 30/11/2017 (2015 days ago), so information in it may no longer be current.

Israeli chemist Raphael Mechoulam is known to many as “the grandfather of cannabis research.”

Mechoulam, with his colleagues, was the first scientist to identify the chemical structure of THC, the primary psychoactive chemical compound in marijuana, in 1964. (They had identified the structure of CBD, another important chemical compound in cannabis, one year earlier.) 

Israeli chemist Raphael Mechoulam is known to many as "the grandfather of cannabis research." (Courtesy of AG / The Hebrew University of Jerusalem)
Israeli chemist Raphael Mechoulam is known to many as "the grandfather of cannabis research." (Courtesy of AG / The Hebrew University of Jerusalem)

Later research by Mechoulam and his colleagues revealed the chemistry of the other unique chemical compounds produced by cannabis plants.

Understanding cannabinoids on a chemical level allowed scientists to explore how they act on the brain. In time, researchers discovered that the human body produces its own cannabinoids, called endocannabinoids, which play an important role in regulating a number of biological functions.

Now 87 years old, Mechoulam remains a professor at the Hebrew University of Jerusalem. The Leaf recently had a chance to interview him by phone at his home in Israel. (This interview has been condensed and edited for clarity.)

The Leaf: You made the decision to investigate cannabis when you were starting out in your academic career, despite the fact that it wasn’t a terribly popular subject for research at that time. You reviewed the old literature on the subject, including 19th-century papers in English, French, German and Russian.   When you were looking through that old research, what did you discover that got you interested in learning more about the chemical structure of cannabis?

Raphael Mechoulam: Yes. Morphine had been isolated from opium in the early 19th century, and its (chemical) structure was identified in 1920s. The same is true of cocaine.

But cannabis, which was at that time certainly as illegal as anything else — surprisingly the chemistry was not well-known, although major scientists had worked on it. But to the best of my knowledge, the active principle had never been isolated in pure form.

So for a chemist like myself, I thought, “Well, if we want to go ahead, we have to know the chemistry much better.”

It’s impossible to do good pharmacology with extracts. One has to have something that one can measure, one can weigh, one can identify, and so on.

So we had to first clarify the chemistry before it would have been possible to go into pharmacology and physiology and then the clinic.

“I am interested in science and the legal use (of cannabis)– I’m not interested in the recreational use.”

TL: If I understand you correctly, you’re saying that what got you interested was the knowledge that didn’t appear in those papers.

RM: Yeah. The chemistry, and therefore all the other things, were not on the level that 20th-century science can accept.

If somebody says, “Well, I used (cannabis) for whatever,” that’s fine. That’s background information. But that’s not science. In science, one has to have well-defined things.

TL: Speaking of science, in your research you’ve seen the potential medical benefits of cannabinoids, and you’ve advocated strongly for more scientific research and more clinical testing. But you never seem to have crossed that line into being an advocate for cannabis itself, like Timothy Leary advocated for LSD and other hallucinogens. Why do you draw that line?

RM: Well, cannabis is not an identified substance. It’s a mixture. And I am interested in science and the legal use — I’m not interested in the recreational use. I’m interested in the medical use, and for medical use, one has to follow a modern medicinal background.

Medicine was completely different in the 19th century, and it’s slowly evolved (into) modern medicine, which is a scientific thing. One has to measure, one has to be able to identify things that in the 19th century were just about impossible with most things.

(Courtesy of AG / The Hebrew University of Jerusalem)
(Courtesy of AG / The Hebrew University of Jerusalem)

TL: You’ve approached your research from a scientific and a medical perspective. But in jurisdictions where cannabis is now legal, a lot of the money is flowing to production of cannabis and for recreational use.

How do you feel about the rise of the legal recreational cannabis industry?

RM: First of all, one has to separate the medicinal from the recreational. These are two completely different things. Medicinal has to be a quantity, evaluation, science, et cetera.

Recreational is a social issue. And a social issue has to be decided by the population of a state (or) whatever. And if, in a certain state, let’s say in Colorado or in Spain or whatever, people decided it should be legal for recreational purposes, so be it. But that’s a social issue. It has very little to do with the science.

As a social issue, we, the population of just about every country, have approved all kinds of toxic things that shouldn’t be there, but that’s the way it is. We have tobacco, we approve whisky with 50 per cent alcohol — pretty toxic. It’s a social issue. Society has to decide whether it wants it or not. That’s it, period. It has nothing to do with the medical side.

If we have a young person, up to the age of 20, use cannabis daily, for example, he has a pretty good chance of causing changes in the way he behaves and the way he does all kinds of things. So low doses of cannabis, well, nothing major happens.

But if it becomes an addiction, especially at a young age, there may be problems.

Incidentally, cannabis does cause addiction in about 10 per cent of the population. Gladly, the addiction is not as strong as opiate addiction.

“Cannabis does cause addiction in about 10 per cent of the population.”

TL: I was watching the documentary about you called “The Scientist,” in which you say: “When one starts research, one never knows how it ends.” Looking back on your career right now, are you happy with how it ended up?

RM: Yes, I believe that it was pretty good. We made some steps that probably I wouldn’t have taken now. But yes, definitely I’m glad we worked first on the phytochemistry, namely the chemistry of the plant itself. Early in the game, we got associated with biologists of various kinds. We did some pretty good work, I hope. That was the first stage.

Mechoulam: "society has to decide whether it wants it or not." (Courtesy of AG / The Hebrew University of Jerusalem)
Mechoulam: "society has to decide whether it wants it or not." (Courtesy of AG / The Hebrew University of Jerusalem)

The second stage was identification of the compounds that our body makes which parallel the activity of THC, the endogenous cannabinoids. And this is of importance because people at (the National Institutes of Health) have stated that the endogenous cannabinoids, the cannabinoid system, is involved in essentially all human diseases, which is a very, very strong statement. So it has become of importance.

And now, we’re mostly working on the third phase, namely, compounds which are chemically closely related to anandamide and are formed by our body. These are endogenous compounds, there are about 100 of them. And most probably, we assume that our body doesn’t waste energy to make these compounds, (they’re) there for a certain reason.

And we’ve investigated quite a few of those, and we found that one of them works against brain damage when it happens. Another one, surprisingly, works against osteoporosis, loss of bone formation and things like that. Another one may be involved in the reaction of the body to addiction, tries to block addictions and maybe nicotine and so on.

So many of these compounds seem to be of general interest, and I assume that our group, many many other groups, will be finding important things in those anandamide-like compounds. Anandamide is one of the two major endogenous cannabinoids that we make.

TL: You’ve had what could be described as a very successful scientific career, and you’ve received a number of awards, distinctions and honorary doctorates. Do you have advice for young scientists starting out in their careers in the field of cannabis and cannabinoid research?

RM: Young scientists — or scientists — should try to solve things of importance. The fact, for example, that we’re making 120 anandamide-like compounds. This has to be solved. It will be clarified. The reason why our body makes all these compounds has to be clarified. And maybe some of these compounds, or better derivatives of those compounds, can be achieved.

So this is what I would tell a young person starting: Try to work on important problems associated with cannabinoids.  @sol_israel

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