The Father of Cannabis: An Exclusive Interview with Dr. Raphael Mechoulam

Were it not for one man’s efforts, the current cannabis landscape would look more like moonscape. There would be no conversations/blogs on cannabis as a curative medicine, there would be very little known pharmacology; certainly there would be much less clinical information regarding the world’s most captivating herb. That man is Dr. Raphael Mechoulam, professor of medicinal chemistry and Natural Products at the Hebrew University, Jerusalem, Israel. He is aptly referred to as the “Father of Cannabis Research.”

While cannabis is illegal for general use in Israel, the Jewish state is considered to be one of the world’s most forward-thinking countries when it comes to medical marijuana, with scientists and researchers flocking there to learn more about the benefits of the drug. This novel attitude is largely due to the intrepid work of Dr. Mechoulam.

We had the privilege to sit down with the 84-year-old to ask him about his life’s work and the state of cannabis in 2015.

What first drew you to cannabis as a potential research subject?

The three major illicit drugs derived from plants were in the past (and still are), opium, coca and cannabis.

Morphine had been isolated from opium early in the 19th century and its very complicated structure was elucidated in the 1920’s by Sir Robert Robinson.

Cocaine was isolated from coca leaves in the middle of the 19th century and the famous chemist Richard Willstatter had been able to describe its unusual structure in the last decade of the 19th century.

The availability of pure materials made possible biochemical, pharmacological and clinical work with these important alkaloids.

Modern scientists refrain from work on mixtures—and crude plant extracts are complicated mixtures—as the results of such research are difficult to reproduce and interpret.

As the active constituent(s) of cannabis was not available in pure form there was very little modern biological and clinical work on it. Hence I decided to try to establish the chemical basis of cannabis action.

At the time what was the general opinion around cannabis as a medicine? Was it being used at all in Israel?

In the 1960’s when we started work on cannabis, there was no use with it as a medicine in Israel and presumably the same in Europe and North America.

In you early research, how many cannabinoids were you aware of existing in the cannabis Sativa L Plant?

We knew that there are many constituents – we could see this with our analytical instruments. Indeed we isolated and elucidated the structures of several new ones, such as cannabigerol, cannabichromene, some cannabinoid acids etc.

Today, over 100 plant cannabinoids are known. Only THC seems to be psychoactive.

With the recent emergence of CBD as a treatment for epilepsy and schizophrenia and the recent studies using isolated CBD, how important is the notion of “the entourage effect” or whole plant medicine in the advancement for cannabis therapeutics?

We discovered and reported the “entourage effect” in 1998. However we still know very little about it. It certainly seems that an entourage effect exists with THC. See our research paper here.

Your work and research in Israel is seen as pioneering, how important has the Government’s co-operation been when coordinating trials for the elderly and soldiers with PSTD? What are the current research guidelines in Israel?

The Government was not actually involved at all.

Today, cannabis research requires approval by the Ministry of Health. I chair the committee that has to give the OK at the Ministry. There are about 10-15 groups working on cannabis (biochemistry, pharmacology, clinical effects and agriculture). There are no guidelines – each researcher does his own planning.

At what point did you and other scientists become aware of the possibility of the Endocannabinoid system existing?

In 1988 Allyn Howlett, with her then graduate student Bill Devane, brought out the first evidence that a cannabinoid receptor exists in the brain. We assumed that a cannabinoid receptor is not formed for the sake of a plant that has compounds that bind to it, but for an endogenous brain ligand. I decided to try to identify it.

After pretty hard work over 2 years we isolated the first endogenous brain cannabinoid; we named it anandamide. It became clear that we are dealing with a novel biochemical system, which is now known as the endocannabinoid system.

Other than CBD and THC, what is singularly the most interesting cannabinoid to you?

Cannabigerol may be an anti-cancer agent; Cannabidivarin may be anti-epileptic; Cannabigerolic acid is the precursor of all cannabinoids.

There is increasing media and scientific interest in the use of cannabinoids in the treatment of cancer, and many are turning to cannabis to combat cancers. When were you first aware of cannabis as holding anti-cancer properties?

There are dozens of publications in vitro and in animals showing that cannabinoids affect cancer cells. There are many anecdotal patient reports that ‘medical cannabis’ is an anti-cancer drug. However, well designed human trials have not been done. It is hard to believe that neither Government agencies nor private foundations have gone ahead or encouraged clinical trials in cancer – but this is a fact! There are no real clinical trials with cannabinoids against any cancer!

Researchers in the field became aware that cannabis affects cancer cells about 20 years ago.

Is there any other plant derived matter or chemicals that trigger apoptosis in cancer cells in the same manner as isolated THC in vitro studies?

There are many plant derived compounds that affect cancer cells. I am not sure whether the mechanisms are the same.

You have stated before you would be against legalisation for recreational use. Do you hold a different view for the use of medical cannabis?

I strongly believe in well-regulated use of cannabis and cannabinoids in medicine. In Israel we have a Ministry of Health office which regulates medical marijuana. There are 22,000 patients that legally get various kinds of cannabis for numerous diseases.

I sit on the Ministry of Health committee that is supposed to oversee the work of the cannabis office. We still have a long way to go but we are trying to do our best. Medical cannabis is approved (and supplied inexpensively) for pain, cancer, some gastrointestinal diseases, PTSD, epilepsy and a few others but not yet for anxiety or depression.

I believe that in democratic countries, social issues (cannabis recreational use) have to be based on their acceptance by society. I understand that in the US above 50% of the population back legalization. In Israel the percentage is presumably much less.

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