Here’s a fact that might surprise you: Cannabis contains THC and CBD. Surprised? Probably not. Even people whose pot literacy is limited to, “Marijuana is evil,” can tell you that.

But how? How is something so scientifically complex common knowledge among non-scientists?

In the 1960s, Raphael Mechoulam and his research team isolated tetrahydrocannabinol (THC) and elucidated cannabidiol (CBD) when studying the plant at the Hebrew University School of Pharmacy. Those discoveries, and many others, ultimately conferred the honorary title “father of cannabis research” upon Mechoulam. From there, his 60+ years of cannabis research endowed humanity with a pharmacological revolution: controlled and even synthesized cannabis-derived medicine.

But we have much else to learn from Mechoulam, too. To discover what his life taught us, Head reviewed transcripts from interviews he gave, along with direct quotations provided secondhand. Here are three lessons we extracted from this father’s wisdom to share for Father’s Day.

Lesson 1: Don’t let anyone or anything stop you from learning.

Raphael Mechoulam, Ph.D., (1931-2023) was born to a Sephardic Jewish family in Sofia, Bulgaria, a country that sided with Germany in World War II. He recalled his childhood during a 2007 interview with the journal “Addiction”:

“Anti-Semitic laws made our life almost unbearable. My father took a position as a physician in a village, with no running water or electricity, hoping that we would be more secure up in the Balkans. We had to move from village to village over the years. My father was sent to a concentration camp in Bulgaria, but luckily we all survived.”

When he was a child, Mechoulam defiantly learned all he could about the war going on around him. In a 2012 interview with ISRAEL21c, he said, “I was a kid then, but it was something we followed day by day despite the fact that Jews were not allowed to have radios.”

Raphael Mechoulam said his young life under the Anti-Semitic laws in Bulgaria made his life almost unbearable.

Raphael Mechoulam said his young life under the Anti-Semitic laws in Bulgaria made his life almost unbearable.

When he was 18, he was all set to follow in his father’s footsteps and become a doctor. However, his family had its sights set on emigrating to Israel, and the Communist government of 1949 Bulgaria wouldn’t allow medical students to leave the country. Consequently, as he explained in an unpublished interview with the “American Journal of Endocannabinoid Medicine,” he changed his field of study to chemical engineering – and away they went.

After he arrived in Israel, Mechoulam’s academic goals were once again obstructed by a geopolitical force. This time, the obstacle was the Arab Legion’s control of the area where Hebrew University laboratories were located on Mount Scopus. Instead, he enlisted in the Israel Defense Forces (IDF) and spent part of his time in service studying insecticides while attached to a research unit.

Photo of Mount Scopus, Jerusalem By Hagai Agmon-Snir/ CC BY-SA 4.0 via Wikimedia Commons

Photo of Mount Scopus, Jerusalem By Hagai Agmon-Snir/ CC BY-SA 4.0 via Wikimedia Commons

Mechoulam went on to earn a master’s degree in biochemistry from Hebrew University and a Ph.D. from the Weizmann Institute of Science. His Ph.D. thesis was on synthetic chemistry, mostly in the field of steroids. Looking back on the fluidity of his academic passions, he told “Addiction”:

“I found research at the borderline of chemistry and biology fascinating. I believed then, and I still believe, that the separation of scientific fields is just an admission of our limited ability to learn and understand several scientific areas. In Nature the border does not exist. If a leaf and a tree were able to think they would not know the difference between chemistry and biology.”

He completed a post-doctoral stay in New York at the Rockefeller Institute, maintaining a focus on the chemistry of compounds in natural products and teetering between chemistry and biology. He and a professor named S.W. Pelletier investigated the structure of some plant triterpenes, foreshadowing his future expertise in terpenes of another kind.

Then, he returned to Israel. It was the early 1960s, and he was on the verge of making a historic discovery – all rooted in refusing to accept that he wasn’t allowed to learn.

Lesson 2: Help sometimes comes from where you’d least expect to find it, so don’t be afraid to ask.

Mechoulam’s focus on the chemistry of natural products, namely plants, is what led to his choosing to focus on cannabis once he was back in Israel. In a 2019 interview with “Epigraph,” he explained his mindset in the early 1960s:

“I was surprised to find out that while morphine had been isolated from opium 150 years previously, and cocaine had been isolated 100 years previously, the chemistry of cannabis was not well known. Some distinguished chemists had worked on it, but the active compound or compounds had never been isolated in pure form, and the structures were not known. In order to understand the pharmacology and do clinical trials, you need a strong chemical basis. That’s why my group started looking at the chemistry of cannabinoids.”

Ah, but where to get an illegal substance from? And equally important, where to get funding to analyze something that’s illegal to even possess?

First, he tried the U.S. government’s National Institutes of Health (NIH), the world’s main funder of biomedical research. In 1963, he applied for an NIH grant, but was turned down. “I was told that they do not support research on cannabis,” he recalled in his “Addiction” interview, “[because] its use was not an American problem. How little did they know!”

So, he and his colleague, Yehiel Gaoni, Ph.D., decided to do what they could on their own at the Weizmann Institute of Science in Rehovot. They were junior faculty members there at the time. The proper way to obtain cannabis for research was to request it through the Israeli Ministry of Health, but neither Mechoulam nor Gaoni knew that. Being resourceful, they simply asked the university’s administrative director for a personal favor through his IDF buddy, now a leader in the Israel Police. The director wasn’t familiar with the Ministry of Health’s authority over such matters, and he agreed to contact his friend, the head of the investigative branch.

He had to vouch for Mechoulam’s character as “reliable” before the cop would agree to help, and the cop was also unaware of the Ministry of Health’s protocols. Once assured of Mechoulam’s reliability, the cop gave him 5 kilograms of seized Lebanese hashish.

Flag of Israel Police / Photo By רונאלדיניו המלך, SA 4.0 via Wikimedia Commons

Flag of Israel Police / Photo By רונאלדיניו המלך, SA 4.0 via Wikimedia Commons

This is, incidentally, Mechoulam’s favorite story to tell. Varying degrees of detail are sprinkled across numerous interviews that he gave. From the “Addiction” interview:

“I took a bus back to Rehovot, nobody in the bus realizing that the smell from my bag was from hashish. Later we found that both the head of the investigative branch of the police and I had broken quite a few laws. The Ministry of Health was in charge of illicit drug licensing and not the police, and I had broken the severe drug laws. Luckily, being ‘reliable’, I just had to apologize.”

Reflecting on how well that had gone, he told ISRAEL21c: “Working in a small country certainly has its positive aspects. It couldn’t have happened in the United States, because the laws were too strict. In Israel there’s a lot of shouting, but in the end you can make it.”

With those 5 kilos, he and Gaoni were able to isolate and identify the plant’s psychoactive component, THC. Not long after that, Mechoulam received a surprise phone call: It was the NIH wanting him to study THC! A U.S. senator’s son had started smoking pot, and he asked the head of pharmacology at the National Institute of Mental Health whether his son was damaging his brain. Having no answer for the senator himself, the pharmacologist knew whom to call upon for help.

From that point forward, for nearly half a century, the NIH reissued biomedical research grants to Mechoulam, but not automatically. When speaking with the “American Journal of Endocannabinoid Medicine,” he reassured them that he had to put in grant proposals and get them evaluated just like anyone else; there were no special favors. He seemed not to mind the bureaucracy though and was very appreciative of the autonomy given to him by NIH when he’d be working.

Thus, it was ultimately two governmental bodies responsible for enforcing the illegality of cannabis – Israel Police and the U.S. government – that helped Mechoulam and his colleagues. And that came about only because Mechoulam took the initiative to ask.

Lesson 3: Just because something hasn’t been done before doesn’t mean it can’t be done at all.

Among Mechoulam’s groundbreaking cannabis discoveries is the use of CBD to treat the seizure disorder epilepsy. Although CBD had been discovered in the 1930s, it was Mechoulam and Brazilian researcher Elisaldo Araujo Carlini who suggested in 1973 – for the first time – that CBD presented anticonvulsant properties in animals. Seven years later, they demonstrated the same in humans. Before this, it was thought that CBD was an inactive cannabinoid. Their discoveries were the first ever to provide evidence that CBD had any effects, let alone that it could treat epilepsy.

For our full coverage of treating epilepsy with CBD, read “A Pulse Check on Epilepsy and Medicinal Cannabis.”

Regrettably, this lifesaving discovery languished for 35 years before returning to the news and laboratories. When Head interviewed David Jakubovic on his documentary “CBD Nation” (2020), he remembered Mechoulam’s exact comments when CBD came into the spotlight in the late 2000s as an effective anticonvulsant to treat Charlotte Figi. Jakubovic shared the following anecdote:

“This man, Jason David, was near suicide because his son at a few months old, started having these really horrifying seizures that would last for hours. He was shaking. He would shake for hours and hours. This guy was just at end of his rope. Cannabis had occurred to him somehow. He saw it on TV or something, and he went to Harborside and to DeAngelo’s and said, ‘Listen, my son is dying. I’m suicidal. My son’s never told me that he loves me because he can’t speak.’ They gave him CBD because they thought that maybe they can try giving— They were afraid to give a child cannabis because they’d never done it before. That was before Charlotte Figi.

“They ended up giving him CBD thinking, ‘Let’s try this,’ because it won’t get him high. He gave it to him. The same day or the next day, the child had no seizures for the first time in his life. There’s just something so powerful about that because it’s just so real. It’s a story that recurs again and again and again. Dr. Raphael Mechoulam says: ‘We knew this 30 or 35 years ago. We’d published this 35 years ago, and no one was listening to us. CBD stops seizures in humans. They knew it.’”

https://headmagazine.com/filmmaker-david-jakubovic-talks-about-his-breakthrough-documentary-cbd-nation/ Read the full transcript from our interview with David Jakubovic here!

Mechoulam went on to play a key role in developing Epidiolex, the first U.S. government-approved CBD-based medication for epilepsy. Approval came in June 2018, and Mechoulam spoke about both CBD and THC while being interviewed by Meir Bialer at the 13th European Congress on Epileptology (Vienna, Austria, August 2018). From his remarks:

“CBD had been isolated by Roger Adams in the US in the 1930s and by Alexander Todd at about the same time, but the structure wasn’t known. So we elucidated the structure of CBD, and we isolated THC in pure form for the first time. … It turns out there are about 100 compounds of the same type – we isolated most of the major ones, but they didn’t turn out to be psychoactive. The only one that was psychoactive was THC. The other compound, cannabidiol (CBD), is found at high levels in most cannabinoid mixtures. … Both THC and CBD have antiepileptic activity; however, CBD can be given at very high doses because it has no side effects. THC above a certain dose can cause side effects; for people who have never used cannabis, that dose can be 5 milligrams.  So we’re not interested in THC as an antiepileptic drug because above a certain dose, there are too many side effects.”

Image Credit: Andrew Weech   

https://headmagazine.com/cbd-vs-thc/

Other cultures have used cannabis’s contents to treat a multitude of ailments for centuries or millennia, so the idea of using cannabis medicinally isn’t what set Mechoulam’s (and his colleagues’) work apart. No, his work broke new ground by circumnavigating legal barriers that had trapped his predecessors in science, chemistry, biology and pharmacology. No one operating within a cannabis-hostile legal system had succeeded at getting that system to relent just long enough to achieve something in medicine – no one, that is, but Raphael Mechoulam.

Summary: Be studious, ambitious and innovative – no matter what.

Mechoulam remained active as a researcher until just a few weeks before he died at 92 on March 10, 2023. He was still speaking at conferences, giving media interviews, laboring tirelessly to defend cannabinoids as medicine and writing numerous articles. He set a wonderful example to follow if you desire a better world and are willing to take part in getting it there.

For Mechoulam’s full story, watch Zach Klein’s biopic “The Scientist: Are We Missing Something?” (2015). The film’s co-producer, Fundación CANNA, posted it free on YouTube here. The “father of cannabis research” has more to say than what this article was limited to, and his words of wisdom deserve generations of audiences.

Kathleen Hearons is a writer, editor, linguist and voice over actor from Los Angeles. She specializes in creative writing and research-intensive analysis and reporting.  

 

 

 

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Bialer, Meir. “Raphael Mechoulam and the history of cannabis research.” Epigraph, Vol. 21, Iss. 1 (Winter 2019). Accessed May 25, 2024. https://www.ilae.org/journals/epigraph/epigraph-vol-21-issue-1-winter-2019/raphael-mechoulam-and-the-history-of-cannabis-research.

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