At 88, the scientist who first isolated THC is still addicted to research, studying the beneficial effects of cannabis on trauma, colitis, autism, and more
It smelled like weed as I walked past a grassy, tree-shaded area recently near a water fountain and benches at Hadassah Medical Center in Ein Kerem, an affiliate of the Hebrew University of Jerusalem. I smirked; the campus atmosphere was quiet and studious, but it seemed even the world’s highest ranking academics like to get high.
Home to a modest medical marijuana program that serves some 40,000 patients, Israel is nonetheless leading the world in cannabis research and, not to mention, cannabis consumption—nearly 30% of the country’s population has tried the stuff in the past year. While cannabis is decriminalized for an amount limited to personal use, weed is as integral to the social fabric here as it is back home in America—but more on that later.
I approached a nondescript building made from Jerusalem stone (all the buildings here are made from Jerusalem stone) that read “The School of Pharmacy בית הספר לרוקחות” above a single glass door. The building was nothing special; neither was the dingy stairwell where I hiked up to the second floor; and neither was the landing, except for a cute poster about “cocaine reward conditioning.” The floor was dedicated to drug research. I circled the gray, sterile corridor twice, passing open doors revealing active chemistry labs (unwashed beakers, test tubes, and other stuff that goes over my head), as I looked for the office of Dr. Raphael Mechoulam.
If the building belonged to High Times magazine, there would have been a red carpet leading up to his doorway. The now-88-year-old scientist was first in the world to isolate tetrahydrocannabinol, or THC—the compound in weed that gets you high (and helps with dozens of medical conditions). In 2011, High Times dubbed Mechoulam “The Man,” and rightfully so: He is the godfather of cannabis medicine. His discovery of the THC molecule in 1964—a year after he isolated the nonintoxicating compound cannabidiol, or CBD—launched a scientific revolution based on the study of cannabinoids, which are chemical compounds that occur naturally in the cannabis plant and endogenously throughout the human body.
Interviewing Mechoulam is every weed journalist’s dream. I tried to act cool, taking in the environment. The walls were lined with file cabinets and bookshelves filled with wide, decades-old binders with handwritten labels (“lipid chemistry,” “patents,” “cancer,” “cannabinoid reviews,” to name a few) along with books on science, cannabis, and other plants. Framed diplomas and awards in English, Hebrew, and even German flanked one corner of the room; in the other hung a black chalkboard with drawings of the THC and CBD molecules. “I can draw them in my sleep,” Mechoulam joked: After 40 minutes together, he had finally warmed up to me.
Initially we had gotten off to a cool start as he reminded me he doesn’t have much time. He had looked at me blankly, “So what can I do for you?”
Why cannabis? I asked him. “For thousands of years, the only drugs available were drugs from plants,” Mechoulam told me. Cannabis has been used for medicinal and spiritual purposes since the beginning of mankind for everything from Queen Elizabeth’s period cramps to religious ceremonies around Latin America and India. “Morphine had been isolated from opium in the early 19th century and cocaine from coca leaves, but the active compound from hashish had never been isolated in pure form,” he continued. “In a small country like Israel, if you want to do significant work, you should try to do something novel.”
There was little interest in cannabis, Mechoulam said, when he first set out to study it. “Perhaps nobody used or smoked marijuana at the time,” he joked, recalling his efforts in the early 1960s to secure grant money from U.S. agencies for research. But then the National Institute of Drug Abuse got back in touch, about a year after Mechoulam approached them. “The son of some senator was caught smoking pot and wanted to know if it would destroy his brain,” he remembered. While cannabis research in the United States remains limited to this day thanks to a federal prohibition on marijuana, NIDA has helped fund Mechoulam’s research for nearly 45 years.
The world’s leading cannabinoid expert was born into a well-to-do Sephardic Jewish family in Sofia, Bulgaria, on Nov. 5, 1930. Mechoulam’s father was a physician and the head of Sofia’s Jewish Hospital before being sent to a concentration camp, which he survived. His mother was educated in Berlin, and raised him with an emphasis on “books, theater, concerts, and medicine.” When WWII broke out, the Mechoulams moved from village to village, as “anti-Semitic laws made our life almost unbearable.” In 1949, they emigrated to Israel.
Mechoulam got his first taste of research during his army service, studying insecticides. He got hooked, calling research “an addiction from which I do not want to be cured.” In 1952, he received his Master of Science in biochemistry from the Hebrew University of Jerusalem and in 1958, his doctorate from the Weizmann Institute in Rehovot. There he began to dabble in cannabis science.
The Israeli police were Mechoulam’s first lead. As Israel didn’t legalize medical cannabis until the 1990s, the authorities were the only entity legally in possession of hashish—then, the most popular form of cannabis in the region. Mechoulam, a young, straightedge academic (to this day, he claims that he doesn’t smoke), was able to convince the police he was reliable enough for them to gift him five kilograms of “superb, smuggled Lebanese hashish.” Such was the beginning of a four-decade relationship.
On the medical front, there is hardly any stigma surrounding cannabis: Israel’s medical program is fully integrated among university research, hospitals, private labs, medical cannabis companies, and the Ministry of Health. The first phase of cannabis research in Israel was on phytocannabinoids, the cannabis plant’s chemical compounds like THC or CBD (which now is expected to be a $22 billion business in the United States alone by 2022). The plant contains about 120 cannabinoids, many of which are now a hot research topic among various academics and private labs throughout Israel, Canada, the United States, and elsewhere.
The second phase of research was on the endocannabinoids anandamide and 2AG. These are compounds similar to those found in the cannabis plant, but which occur naturally in the human body. The body’s endocannabinoid system regulates a host of physiological functions, including sleep, pain, inflammation, mood, and appetite. “ have a different chemical structure than plant cannabinoids, but the same type of activity, which is not unusual,” Mechoulam explained.
Mechoulam and his colleagues discovered the endocannabinoid, anandamide, sometimes called the “bliss molecule,” in the 1990s, and named it after the Sanskrit word ananda, meaning supreme joy. “We looked for a Hebrew name,” Mechoulam joked, “but as you may well be aware, Jews are not very happy. We have a lot of words for being down and so on, but not so many words for extreme joy.”
Hashish arrived in the Middle East during the Middle Ages, thanks to merchants returning from lands like India, where cannabis, mainly in the form of charras or hash, was and is a popular sacrament among Hindu devotees of the Lord Shiva. (Cannabis, in hemp and flower form plays no small role in Jewish practice, as well, beginning in biblical times, but that’s another story.) By the early 20th century, Egypt had become the main consumer of hashish, with Greece having been the main provider. But as a new middle class in Egypt developed “hand in hand with the British occupation,” they saw hashish as a “lower class drug,” Haggai Ram, professor of history and Middle Eastern studies at Ben-Gurion University in the Negev, explained to me. Hashish was banned in 1925, and within a decade, Greece followed suit. Lebanon and Syria then surfaced as new primary suppliers of black market hashish moving toward Egypt.
As the through route from Lebanon to Egypt, “Palestine was officially the largest depot of hashish in the Levant in the interwar years, a theater of intensive and dramatic smuggling or trafficking operations,” said Ram. “As it always happens, some of that merchandise remained in Palestine for home consumption, actually creating a market for hashish.”
Israel-Palestine witnessed a spike in hashish smoking during the 1920s and ’30s. Ram noted: “You have in every Palestinian city—Jaffa, Jerusalem, Tiberias, Acre—multiple venues of hashish smoking, such as hashish dens, cafés, and coffee houses, which served hashish to customers.” Arab, or Mizrahi, Jews took part in hashish culture alongside their Muslim and Christian neighbors, as the Holy Land became the Amsterdam of the Middle East. “People could be seen in the streets intoxicated the police had no real interest in hashish enforcement,” he continued. “They had other priorities: Jewish immigration and Arab revolt.”
Ashkenazi Jews who immigrated to the land looked down on hashish, much the same as the British-inspired middle-class Egyptians did. And so there was a movement to dissociate the Arab Jews from hashish as a means of dissociating them from Palestinian culture. “During the mandate period, the Zionists rapidly endorsed humus, seeing it as an authentic dish, but hashish was a wholly different matter,” said Ram. “Using hashish would cross a border which should not be crossed because it could make you an Arab. It became an important distinguishing mark between Jews and Arabs.”
But the dissociation of Jews from cannabis lasted only briefly after 1948. Jews from Arab and North African countries immigrated to Israel, bringing their own customs from back home, and settling in transit camps, where it was found in the early 1950s that they were growing their own cannabis for home consumption. “They suffered from poor sanitary and hygiene conditions, poverty, and neglect, as well as ill-treatment and discrimination by the state,” Ram writes in an article titled “Hashishophobia and the Jewish ethnic question in mandatory Palestine and the State of Israel,” published in the British Journal of Middle Eastern Studies. “Beset by these adversities, transit camps soon evolved into centers of drug wheeling and dealing and substance abuse.”
Mechoulam’s luck in procuring his research materials was therefore a byproduct of Israel’s own drug war—a campaign that continues to disproportionately affect Arabs and Mizrahi Jews in a manner similar to how in America blacks are almost four times more likely than whites to be arrested for cannabis despite comparable rates of use. Yet by the 1960s, hashish smoking spread among Ashkenazim, too, as part of a global movement whereby cannabis fueled the growing counterculture. Immediately after 1967, hashish wholesalers, especially in East Jerusalem, redirected their merchandise from Egypt to the local market, bringing an increase in customers, Ram explained. “But more than that, the occupation of Jerusalem and the West Bank also gives Israeli smokers or would-be smokers direct access to the market, so Jerusalem after 1967 becomes a mecca of hashish in Israel,” he said. “The substance loses its distinctly primitive, oriental connotations and Israel opens up to the global scene.” By the 2000s, Israel was dubbed a “nation of stoners” in Haaretz.
In my own man-on-the-street reporting with an Arabic translator throughout East Jerusalem and Bethlehem, indeed it seems that since the second intifada, a rise in right-wing politics and religious fanaticism among both Israelis and Palestinians has led to more conservative attitudes toward cannabis, especially among the latter group, and there remains a stigma around cannabis in Palestinian communities, though an underground culture of consumers does exist. Four different strangers in East Jerusalem referred to a conspiracy theory painting Israeli efforts to legalize weed as an attempt to make Palestinians too lazy to fight back.
Israelis, however, from all walks of life, religion, and politics, have come to accept cannabis, at the least, as a medicine. Even former Prime Ministers Ehud Barak and Ehud Olmert have both joined Israel’s medical cannabis industry, while ever since the Lebanon War, cannabis flower has replaced hashish as a homegrown alternative to “supporting Hezbollah.” There were also fears about imported hashish being poisoned, Liel Maghen, co-director of the Israel Palestine Center for Regional Initiatives, explained to me one night in Jaffa over shisha and kanafeh. A cannabis-fueled way of life for Israelis grew into a way to deal with, or escape from, the micro and macro episodes of trauma that come with living in an intermittent war zone. On a Thursday night in March, Iron Dome intercepted a rocket aimed for Tel Aviv. I heard the explosion, got tea with a Maghen, went to a concert, and hung out with him and others till the wee hours of morning getting high in a cloud of never-ending pot smoke. Everyone was high, and perhaps, also, silently anxious. Life goes on, and the approach seems to be living life more intensely.
The war with Lebanon, then the wall built between Israel and Sinai, and the proliferation of medical cannabis permits (with diversion of pre-rolled joints from the medical program to the black market) have all led to a greater amount of Israeli-grown flower, rather than hashish, on the market. Kibbutzim have taken to growing weed, while Israelis returning from their post-army trips to India bring back the drug culture savored on the beaches of Goa.
So suffice it to say, it’s easy enough to get weed in Israel these days. Make a call, send a text, you’ll get your delivery within an hour. The most popular platform has been Telegrass, something of an Uber for weed dealing: The app lives on the anonymous messaging platform Telegram. Israeli authorities have been going after leading dealers on Telegrass for years: They successfully arrested founder Amos Dov Silver in Kiev in March, and he told me last year that Telegrass “is stronger than me by now,” and he’s right. The phone app is already back in use, despite the raid. So are several other similar apps on Telegram like GetWeed or Weed4U.
As for your everyday consumer, cannabis is decriminalized for possession of up to 15 grams. About 90% of the populace supports decriminalization, said Oren Lebovitch, head of Ale Yarok (Green Leaf), Israel’s cannabis legalization party, while at least 100,000 voters support full-on legalization. Even Prime Minister Benjamin Netanyahu has said he would seriously consider the issue “soon.”
But there’s a tension in Israel between proponents of medical cannabis and full legalization. “If you look back at the people who brought the whole idea of medical cannabis to the world, they were legalization activists, so the patients owed them,” Lebovitch said. “And the other way around: Thanks to the medical cannabis patients, the legalization idea went much further. People saw, ‘OK, it’s not that bad, cannabis can help people.’ It softens the stigma.”
Now in the third phase of his research, Mechoulam is currently investigating other endogenous compounds related to anandamide, the endocannabinoid he discovered more than 20 years ago. These compounds have implications for a wide range of indications for everything from head injury to osteoporosis to addiction. In particular, anandamide is integral to autism.
“In autism, the levels of anandamide are low,” Mechoulam said. “And yes, CBD is an excellent anti-autism drug.” That’s because CBD inhibits an enzyme called FAAH, which breaks down anandamide. But when anandamide can’t be broken down, it accumulates in the brain—which is exactly why CBD is especially helpful for people, like autism patients, with anandamide deficiency.
To learn more about Israeli research on cannabis and autism, I caught a ride from Tel Aviv to Rishon Lezion with Ma’ayan Weisberg, who leads international relations and business development for Tikun Olam, Israel’s largest medical cannabis provider, to meet with the company’s medical director, Lihi Bar-Lev Schleider, in the Assaf Harofeh Medical Center. Schleider established the research department of Tikun Olam a dozen years ago, initially focusing on cannabis for Crohn’s disease and colitis. We ordered Aroma coffee, as she ran through her research on autism, which has spiked in prevalence by 15% in the United States alone.
A study on the effects of high-THC joints in 2010 revealed the efficacy of cannabis for spasticity and dystonia, and increased quality of life and personal interactions in patients, which led researchers to plan autism trials. As recently as this year, Schleider published a study on cannabis for 188 children diagnosed with the disorder. “We saw that more than 90% of patients who suffered from agitation, aggressive behavior, and restlessness reported improvement in those symptoms,” she said. Some even reduced their use of other pharmaceutical medications.
But, Schleider cautioned, cannabis “is not a miracle, it’s not a one drug fits all.” She and her colleagues are working diligently to understand how different patients (even with the same condition) interact with different cannabis strains, or plant varieties with different ratios of cannabinoids and terpenes (aromatic compounds). “There’s a whole aspect of genetic evaluation, which I hope will help us understand who are the patients who will benefit the most and who will be most likely to withdraw from the treatment,” she said. “It’s not one drug for each condition. It really depends on symptoms.”
In collaboration with Israeli hospitals and universities, Tikun Olam and other medical cannabis companies are developing pharmaceutical-grade treatments, with consistent effects as flower (pre-rolled joints), oil, tinctures, and other products. “Tikun Olam has a very heavy meaning that we’ve taken on our shoulders,” Weisberg said. “The clinical trials we’re doing here are not just for ourselves. Every trial Lihi does gets published and that reaches doctors and changes the legitimacy and way the medical world perceives , so more patients can have access to it, whether in Israel or outside Israel.” Indeed, Tikun Olam has American outposts in states like Florida, California, and Delaware.
“Israel is one of the leading countries in the world in cannabinoid research, and the reason for that is because we started when nobody else was doing it,” Mechoulam told me. “In the next decade or maybe less, we shall have cannabinoid drugs on the market,” he said. “By drugs, I mean compounds that have been looked into, that have gone through clinical trials that are parallel to any other drug. We can have that for disease like depression, schizophrenia, anxiety, post-trauma.”
In a land especially wracked with trauma, perhaps it’s fitting that the Holy Land, the homeland to different peoples, is the homeland of cannabis research, too. “Cannabis works, no doubt about it. It works,” Mechoulam is famous for saying. “Essentially in every disease that has been investigated, the endogenous cannabinoid system is involved.”
Editor’s note: The following excerpt from the website Green/Entrepreneur’s April 25, 2019 article on ‘How Israel Became the Global Leader in Cannabis Research’ has a revealing spotlight on Hebrew U’s Multidisciplinary Center for Cannabinoid Research and how they are following in Prof. Mechoulam’s footsteps.
Mechoulam and other researchers’ isolation of CBD and THC in marijuana led to more research on the psychological and physical impact of both on humans. By the 1990s, there was government-backed research in Israel, decades ahead of most other countries.
In 2017, the School of Pharmacy at Hebrew University founded the Multidisciplinary Center for Cannabinoid Research. The center, which employs 27 cannabis researchers, lauds Mechoulam’s early work, which “heralded in a new age with a promising new vision for humankind.”
The center focuses marijuana research into these areas:
- Inflammation and stress management
- Drug delivery and nanotechnology
- Pharmaceutical chemistry
- Plant science and genetics
While not the only country ahead of the U.S. in research, Israel is certainly considered the one that is the farthest ahead. And with the European Review of Medical and Pharmacological Sciences reporting advances in marijuana research in Italy and other European countries, the U.S. runs the risk of falling even farther behind.