Raphael Mechoulam, scientist who discovered why cannabis makes people ‘high’ – obituary

Professor Raphael Mechoulam, who has died aged 92, paved the way for cannabis research in the 1960s by isolating and synthesising tetrahydrocannabinol (THC), the main psychoactive ingredient of marijuana.

Later, in the 1990s, he identified the brain’s endocannabinoid system, which plays a role in mood, memory and the sensation of pain and is receptive to THC, accounting for the “high” feeling experienced by those who use marijuana recreationally.

His research led to Israel, where medical marijuana is approved for around 27,000 patients, becoming the world leader in medical cannabis research.

The son of a doctor, Raphael Mechoulam was born into a Sephardic Jewish family in Sofia, Bulgaria, on November 5 1930. During the war, when Bulgaria allied with Germany, his father was sent to a concentration camp, from which he was eventually released, and in 1949 the family emigrated to Israel.

After taking a degree in biochemistry at the Hebrew University, Mechoulam spent two years in the early 1950s working in an Israeli Army medical research unit. In the early 1960s he took an academic post at the Weizmann Institute, completing a PhD on the chemistry of steroids.

He became interested in cannabis after local police handed him five kilos of the drug, seized from traffickers. “Morphine had been isolated from opium in the early 19th century, cocaine had been isolated from coca leaves in the mid-19th century,” he recalled, “and here we were in the mid-20th century and yet the chemistry of cannabis was not known.”

In 1964 Mechoulam extracted and identified THC, though knowing the chemical structure did not show how cannabis produces its effects. A frequent visitor to the US, he applied for a National Institute of Health (NIH) grant, but the hippie era had not yet dawned and he was turned down. Later in the decade, however, NIH representatives flew to Israel to find out about his work.

Mechoulam had also re-isolated another ingredient of cannabis, cannabidiol (CBD, originally discovered in 1940) a substance with no psychoactive effects which is now widely used in herbal medicine, though its claimed therapeutic effects are disputed.

For many years Mechoulam and his team collaborated with a group led by Roger Pertwee of Aberdeen University with whom, in the early 1990s, he reported the discovery of anandamide, a so-called endocannabinoid which is believed to act as the body’s natural cannabis. They showed that THC works by mimicking a chemical that occurs naturally in the human brain.

Mechoulam became an advocate for the use of cannabis derivatives in easing symptoms of cancers, epilepsy and other diseases, and regretted that drug laws in the US, UK and other countries had kept many such drugs off the market. In 2018, however, the British law changed to allow the prescribing of cannabis-based medicinal products in certain circumstances.

But Mechoulam was rigorous in being guided by the scientific evidence. While he found that symptoms of type 1 diabetes could be helped by CBD, he warned against the use of cannabis by Alzheimer’s patients because THC could have damaging effects on memory.

In other research, in 2008 Mechoulam showed that frankincense, the resin of the Boswellia tree, contains a constituent called incensole acetate which helped reduce anxiety and depressive symptoms in mice, suggesting that its use in religious ceremonies might confer more than simply spiritual benefits.

Despite being described as the “grandfather of medical marijuana research,” Mechoulam claimed that he had never smoked a joint.

Mechoulam is survived by his wife Dalia, and by two daughters and a son.

Raphael Mechoulam, born November 5 1930, died March 9 2023