Raphael Mechoulam, renowned Israeli chemist and pioneer in cannabis research, passed away on March 9 at the age of 92, after devoting his life to finding ways to alleviate people’s pain and suffering. He is survived by his wife, Dalia, with whom he traveled everywhere, and three children and seven grandchildren. Because of Mechoulam’s discoveries, cannabis is no longer thought of as solely a recreational drug but as a medicinal herb with potential that he found the keys to unlock.
Mechoulam was the first scientist to isolate cannabinoids, natural pain-alleviating chemicals that affect the central nervous system and the immune system, from hashish, the most concentrated product of the cannabis plant. In 1963, Mechoulam and Professor Yuval Shvo isolated CBD (cannabidiol), which is widely used today for pain and illness. A year later, he and Professor Yechiel Gaoni isolated the psychoactive plant cannabinoid THC (tetrahydrocannabinol). CBD and THC are used to treat a wide range of disorders and illnesses, including epilepsy, HIV, addiction, autism, anxiety, ALS, cancer, PTSD, Parkinson’s disease, Alzheimer’s, multiple sclerosis and even traumatic brain injuries. Mechoulam also defined the endocannabinoid system, which is known as the “supercomputer that regulates homeostasis in the human body” because it helps to modulate appetite, mood, memory and the sensation of pain. It interacts with substances found in cannabis.
Mechoulam was born in Sofia, Bulgaria, in 1930 to a Sephardic Jewish family. During World War II, when anti-Jewish laws were put into effect, Mechoulum’s father, a physician, relocated his family to various small villages where he felt it would be safer for them to live. He was sent to a concentration camp, and when it was burned down, he was the only doctor there who could help others and he was released afterwards. Like many other Bulgarian Jewish families, Mechoulam and his parents made aliyah after the war in 1949.
While he served in the IDF, Mechoulam researched insecticides. He received his master’s degree in biochemistry from the Hebrew University of Jerusalem and his Ph.D. from the Weizmann Institute of Science, where he studied the biological function of natural products. He joined Weizmann’s scientific staff after completing his postdoctoral studies at Rockefeller Institute in New York City. In 1972, he became a professor of medicinal chemistry and then a rector at Hebrew University, where he was also head of the Medicinal Chemistry Lab. He continued working at the lab past his retirement until the very end of his life.
Mechoulam is a founding member of the International Association for Cannabinoid Medicines and the International Cannabinoid Research Society, and he was elected to the Israel Academy of Sciences and Humanities in 1994. He received over 25 academic awards around the world, including the Harvey Prize from Technion in 2020, which is a predictor of the Nobel Prize.
In 2000, Israeli filmmaker Zach Klein’s mother was undergoing chemotherapy treatment for breast cancer, and her oncologist recommended she be treated with cannabis to mitigate side effects from the chemotherapy. Cannabis was illegal then in Israel, and there was a false idea that it caused brain damage. Klein heard about Mechoulam being honored with the Israel Prize in Exact Sciences – Chemistry, and decided to investigate by attending a conference held by Mechoulam in Tel Aviv. Speaking to The Jewish Press, he described his experience at the conference as “mind-blowing.”
Mechoulam assured him that cannabis would not cause brain damage – in fact, studies he was involved with showed that cannabinoids can decrease the amount of tissue damage after a brain injury.
Klein obtained cannabis for his mother from the black market, and it immediately provided her with relief. He reported, “Side effects alleviated by cannabis for my mother (included) nausea, appetite, sleep and mood. It made her more optimistic. When she recovered, she started her Ph.D. at Tel Aviv University.” In 1995, Mechoulam collaborated on a research study with Drs. Ava Abrahamov and Dr. Avraham Abrahamov in Israel, who successfully treated children who were experiencing nausea and vomiting from chemotherapy. No significant side effects were reported.
Klein developed a friendship and work relationship with Mechoulam over the years, and he was so inspired by his mother’s experience that he immersed himself in the field of cannabis research.
In 2009, Klein directed Prescribed Grass, a film Mechoulam agreed to be in but not star in. Klein remembered, “The first thing I said to Mechoulam was, ‘I want to make a movie about you’…Immediately he said, ‘No…you should make a movie about the medical use of cannabis…make a movie so doctors and the public will know what’s going on.’”
The film shows footage of a man with Parkinson’s disease whose hand trembles uncontrollably as he makes frustrated attempts to write. Seconds after he inhales medical marijuana, he becomes noticeably relaxed, his hands are steady and he is able to write legibly. The immediate change in him is dramatic and miraculous.
Prescribed Grass premiered on Israeli television when a medical cannabis movement was starting in Israel, and the day after it aired “all the phones at the Ministry of Health collapsed,” Klein said. Parents of a young severely autistic boy contacted Klein after they saw the film, and he and Mechoulam met with them to discuss cannabis as a treatment option for him. After one month of using cannabis, “They came back to show the miracle that happened.” Klein said, “Since then, when I came to Mechoulam, he was always asking, ‘How is the little boy? How is he doing?” Mechoulam wrote a letter to the Ministry of Health advocating for the boy to be treated with cannabis, which he continues to receive to this day. Other autistic children in Israel have access to cannabis because of his experience.
From 2010 to 2013, Klein obtained permission from the Ministry of Health to bring cannabis to nursing home patients suffering from Parkinson’s disease and Alzheimer’s, and recovering from stroke. Mechoulam oversaw the project.
Klein explained, “Most of the people were sitting in wheelchairs, most of them cannot even eat by themselves. They (were on) many different medications that caused side effects. When cannabis was introduced, the medical staff saw people who were very irritated become very calm, some of them started to communicate better, get better sleep, they have better appetites…the nursing home became famous.” Nursing home residents in Israel are being treated with cannabis to this day because of the success of the study.
Recognizing how a film can open doors for new ways cannabis could be widely used, Mechoulam agreed to Klein directing a second documentary about his life and his discoveries. The Scientist debuted online in 2015 and remains available for public viewing. It begins by showing how Mechoulam obtained marijuana that had been confiscated by police and brought it back to his laboratory to study. Mechoulam’s lighthearted and engaging personality comes through in the footage. When Klein asks Mechoulam if he’s okay, he humorously replies, “What can we expect from a day that begins with getting up?”
One of Mechoulam’s most groundbreaking discoveries was that cannabis can stop seizures in people with epilepsy. In The Scientist, Mechoulam tells of a story about an Arab leader in the fifteenth century who had been cured of epilepsy as long as he continued to take the cannabis a physician administered to him. Mechoulam stated, “We first tried it on animals and it worked, so at this point we decided to go into humans. (The) trial took place in Sao Paolo. They had about ten people that had epilepsy that could not be affected by the known drugs. We started giving them high doses of cannabidiol, 200 mg. per day. We were happy to note that indeed they had no seizures while they were taking cannabidiol, and it was published (in 1980) and nothing happened afterward. So far, 34 years later, this is the only publication of cannabidiol in humans against epilepsy.”
Mechoulam’s close friend and colleague, pediatric neurologist and psychopharmacology researcher Dr. Ethan Russo, worked with Mechoulam as an advisor to GW Pharmaceuticals (now Jazz Pharmaceuticals) in the early 2000s, which was one of the primary funders of biomedical research into cannabinoids. He said that Mechoulam “was very much invested in the idea that there should be therapeutic applications [of cannabis],” but nothing happened for many years after the epilepsy study because in the 80s, and for many years thereafter, it was virtually impossible to do any clinical research on cannabis because of its Schedule One forbidden status… Even today, if I want to study cannabis in the clinic, you need a Drug Enforcement Administration permit, which is a hard thing to get. The material has to be stored in a locked safe inside a locked refrigerator inside a locked door with limited access. It’s extremely stringent.”
Dr. Russo was directly involved, and Mechoulam peripherally, in the initial stages of clinical trials of Epidolex, a 98 percent pure cannabidiol medication manufactured by GW Pharmaceuticals used to treat different forms of epilepsy, including epileptic seizures in infants and children. Epidolex was FDA approved in 2018 and is also available in other countries.
Dr. Russo stated, “None of the drugs that Rafi developed himself have yet gone into commercial production…. However, the story is not over yet because he made many substances.”
Israel patent attorney and U.S. patent agent Avraham Hermon met Mechoulam in the early 2000s while working for a company that was developing some of Mechoulam’s synthetic cannabinoid derivates. Referencing the parshah that was read the week Mechoulam passed away, Hermon said, “Last week’s Torah portion mentioned the ingredients of holy anointing oil…There are four ingredients, according to our rabbis…There are some that say there’s one ingredient (in Hebrew) called qěnēh bośem, which people associate with cannabis because it sounds similar to cannabis…It is in Exodus 30:23.”
