Reigning Researcher The father of THC, Dr. Raphael Mechoulam, talks about his groundbreaking research in studying cannabis in Israel

Photos by Yitz Woolf

In the early 1960s, though cannabis had been used for centuries and demonized for decades by governments around the globe, the science world knew surprisingly little about the plant itself.

Scientists had long since learned how to synthesize morphine from the opium poppy and cocaine from coca leaves, but what about cannabis? Few in the U.S. or the rest of the Western world cared to learn about cannabis—not that they could study it anyway, given harsh restrictions cannabis research in the U.S.

So it should come as no surprise that some of the major breakthroughs in understanding cannabis came from across the ocean. In the tiny nation of Israel, one man, Dr. Raphael Mechoulam, is responsible for much of what we know about cannabis today. He was the one who isolated and identified cannabidiol (CBD) and tetrahydrocannabinol (THC), the psychoactive ingredient in cannabis. He later identified the receptors in the human body that interact with cannabis and the cannabinoids that bond with those receptors.

“First, elucidation of the chemistry, particularly isolation and synthesis of the active compounds. It turned out there was only one active compound related to psychoactivity, THC. There is a second that had a lot of therapeutic effects called cannabidiol, and we elucidated its structure as well.”

While the world is just waking up to the medical potential of cannabis, from treating epilepsy to cancer to chronic pain, Dr. Mechoulam has known about it for decades. At 86, he has earned the distinction of being the “father of marijuana research” and the “father of THC.”

Dr. Mechoulam may be one of the world’s foremost experts on cannabis, but he is no advocate scientist in the vein of Timothy Leary or Terrence McKenna. He approached cannabis with the curiosity of an organic chemist studying something new, not as a true believer. In fact, except for in the laboratory, he’s never even touched cannabis.

CULTURE recently caught up with Dr. Mechoulam in Israel, where he still holds several academic posts, including Professor at Hebrew University of Jerusalem in Israel, and advisor to the government on Israel’s medical cannabis program.

How did you get involved in cannabis research?

I’m a chemist. I work with natural products, and I was looking for something important in natural products in plants, and I was surprised to find out that while morphine had been isolated from opium nearly 150 years previously and so was cocaine, from coca leaves, the chemistry of cannabis was not well-known, and I thought it was a good topic to do research on.

Did you have any personal experience with cannabis, or was it non-existent in Israel at the time?

No, no, no. Very few people were interested in marijuana at that time. As a natural scientist I asked for a grant from the (U.S.) National Institute of Health (NIH), and more or less what they told me was they were not interested, that marijuana was not an interesting topic for them. Few people used it in the States. It was mostly used in Mexico, so if I found something that was more relevant to the U.S. so they would look at it. It was in the early ’60s. Well it turned out all of a sudden it became relevant (with the rise in use in the later 1960s), and pharmacologists from the National Institute of Mental Health and the NIH flew over and at that time we had isolated the main component of cannabis, THC, in a pure form . . . and [one pharmacologist] took that material, and quite a bit of the early work of the NIH with cannabis was done with the THC we gave him. He may have smuggled it into the U.S., I don’t know.

“There is a lot of interest, and I believe this is the third phase of cannabis research. But most people in the States are interested in the first stage, in the THC, in the CBD, in selling it for outrageous prices and trying to make a lot of money out of it.”

You had to get smuggled cannabis for your first experiments, correct?

I didn’t get marijuana; I got hashish from the police.

And how did that happen?

Not that complicated at all. I went to the administrative head of my institute and asked him whether he had a contact with the police and he said, ‘Sure, no problem.’ He called the number two person at the police at that time. They had been in the army together or something of that sort. From the other side I could hear him saying, “Is he reliable?” And the head of the institute said, “Of course he’s reliable.” So he invited me over to the police, and I took five kilos of hashish. It broke the laws. It turned out I was not allowed to have it, and he was not allowed to give it to me. It was the Ministry of Health that should have permitted it, but in a small country, I went to the Ministry of Health, and I apologized, and any time I needed more hashish I went to the Ministry of Health and had no problems.

What were you really hoping to learn about this substance when you started to study it?

I’m a chemist. A natural products chemist usually works on identification of compounds, active compounds, and thus opening the field for further research . . . I’ll try to explain. In order to do biochemistry or pharmacology or clinical work, the chemistry has to be well-known . . . The chemistry has to be well-established before anything can be done with the compound or the plant. In this case the chemistry was not well-known so we knew at that time, in the early ’60s, very little about the pharmacology and the chemical effects and so on, in modern terms. Science has to be quantitative. If you work with a plant, you never know what you’re doing, what you’re getting. So the chemistry had to be established before anything scientific could be worked on.

How long did it take you to establish the chemistry and start to look at the human effects of this plant?

For several years we worked on the isolation of compounds, several different types of compounds. With biologists we evaluated the effects on monkeys and later, after quite some time, we worked on the metabolism. Later we worked on other topics. So we advanced, step-by-step.

What do you feel were your major breakthroughs and discoveries about this plant?

First, elucidation of the chemistry, particularly isolation and synthesis of the active compounds. It turned out there was only one active compound related to psychoactivity, THC. There is a second that had a lot of therapeutic effects called cannabidiol, and we elucidated its structure as well. So this was the first phase of the cannabis research we did. Later on, many years later, we looked at the compounds that our bodies make, and these compounds bind with the same receptor that the plant cannabinoids bind to . . . The receptors don’t exist because there is a plant out there. The receptors exist because we produce compounds which bind to these receptors, activate them and cause activities. We went ahead looking at the compounds that we make. Then in the ’90s we discovered that the two main compounds that bind to these receptors, anandamide and 2-AG, and there has been a huge, huge amount of work on these endogenous cannabinoids, cannabinoids that we make . . . These compounds seem to be very important in our biology. One of these compounds has to do with bones and osteoporosis, loss of bones, and another has to do with blood vessels during head trauma and so on. A third one has to do with addiction. And so on and so forth. There is a lot of interest, and I believe this is the third phase of cannabis research. But most people in the States are interested in the first stage, in the THC, in the CBD, in selling it for outrageous prices and trying to make a lot of money out of it.

Do you feel that by focusing on selling expensive flower, that the United States is missing out on some important things about this plant?

The plant contains THC and a lot of other compounds that do not cause the high. There is a compound called CBD, which is just as important. It does not cause the high but it has a lot of therapeutic effects, and it is of extreme importance, and people are trying now to have plants that don’t have THC but CBD and are using that for therapeutic effects.

When you started studying this, were your colleagues skeptical, or did you have a lot of support in the scientific community?

We went along scientific lines. There was no objection at my university. As a matter of fact people thought it was as a good kind of research, interesting research. And even my colleagues, in the late 1970s or early 1980s, elected me Rector of the university. If they had any objections to my work they wouldn’t have voted for me. I was elected to the Israeli Academy of Sciences. If there was any objection I wouldn’t have been elected.

Are you still studying cannabis?

Now I am officially retired, but my university is a very liberal one, and I have all the faculties to go on working . . . We’re not studying cannabis, the plant. We haven’t studied the plant in many years. That was the first stage.

Did you play a role in Israel allowing medical cannabis?

I’m a Consultant for the Ministry of Health, and the Ministry of Health has approved medical marijuana under strict regulation. There are about 27,000 patients who get medical marijuana. We are trying to improve and know exactly what kind of marijuana should be given for a specific condition. One does not get the same marijuana for epilepsy and for cancer and pain.

How do you feel about being called the “father of marijuana research?” Is that something you’re proud of?

Well I’m delighted that I’m called that. We have apparently done something good in the field.

“We are trying to improve and know exactly what kind of marijuana should be given for a specific condition. One does not get the same marijuana for epilepsy and for cancer and pain.”

Is this the type of research that could only have occurred in a small country like Israel?

I have no idea. As an academic I decided to do it, and I did it. Here it was maybe easier to get the material, but I had no problems doing the science. Possibly in the U.S. it would have been more difficult because of administrative problems, but we had no problem getting the materials or other major problems at all.

Is there more to learn about the cannabis plant and how it affects humans?

Because of administrative freezes [on research], there have been very, very few clinical studies. Although thousands of people use cannabis to fight cancer, there hasn’t been any clinical study, or a well-done, modern clinical study on cancer published. That’s a shame because if people use it, the data should be there. We should have modern clinical data. We did some clinical work on epilepsy 35 years ago and unfortunately nobody took great interest in that. And only five or six years ago all of a sudden people found that yes, our research is very relevant to what’s going on and many children today are being treated today with CBD, which we showed to be very active against epilepsy. There are very few drugs that help children with epilepsy. This should have been repeated on a larger scale in the U.S. We did a little work on PTSD and post-trauma. It should have been done on a large scale . . . All these things should have been done in the U.S. There is a major clinical trial on epilepsy. It should have been done 30 years ago after we published our small clinical paper. So that’s what’s missing. And I’m sorry about the situation.

My last question is do you use it yourself?

No. I have never used it. First of all, I am still interested but as I did research and we had official supply of cannabis, obviously if we had used it for non-scientific reasons if people had come to know about it that would have stopped our work. Basically, neither I nor my students were interested.

medicine.ekmd.huji.ac.il

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