The Hebrew University of Jerusalem can justifiably boast that it has done more for cannabis research than any other scientific institution in the world.
Bulgarian-born Prof. Raphael Mechoulam, 91, is a still-active organic chemist and professor of medicinal chemistry at the university who has studied cannabis (marijuana) for more than five decades. In 1976, he and his team succeeded in synthesizing tetrahydrocannabinol (THC), the psychoactive compound in cannabis.
Mechoulam – who has received the Israel Prize, Harvey Prize, Rothschild Prize and many others awards for his research – has since made major contributions to the chemistry of cannabinoids and the discovery of endocannabinoids. Those molecules produced by the body are similar to cannabinoids of plant origin in that they tend to make people happy. Also called endogenous cannabinoids, the first was named anandamide by Mechoulam, after ananda, the Sanskrit word for joy, bliss and happiness.
He and his research group also succeeded in the total synthesis of the cannabidiol (CBD), a chemical in the cannabis sativa plant (hemp) that in one form is approved as a drug for seizure. They also synthesized cannabigerol (CBG), which may help lower cholesterol, protect the brain and nerves and reduce swelling and may help against Huntington disease, inflammatory bowel disease and to stimulate appetite.
In his initial study of natural products, Mechoulam was surprised to learn that the active compound in cannabis had never been isolated in pure form. He decided to investigate its chemistry, because without an active chemical, it could be used for basic or clinical research. He recalled that the US National Institutes of Health (NIH) were not interested in giving him grants because they said, “Marijuana is smoked in Mexico, not the US.” However, after a senior American politician learned that his son smoked it and feared it had affected his brain, the NIH changed its mind. The Health Ministry in Jerusalem finally granted Mechoulam permission to obtain cannabis samples from the Israel Police so he wouldn’t be jailed.
Lacking a car then, he took the weed to his lab by bus, arousing queries from fellow passengers about what was producing that sweet smell.
As it is not psychoactive, CBD can be used in large amounts. Mechoulam’s medical colleagues found that it could stop epileptic attacks in half of young epilepsy patients. Conducting a large clinical trial on children with epilepsy, though, had to wait for 35 years. He called this delay unfortunate, as many thousands of children could have been helped.
There should be a complete separation between medical cannabis and recreational cannabis; it has to be regulated according to medical principles.
Prof. Raphael Mechoulam
THROUGHOUT THE world, the cannabis plant is now gaining in popularity and legitimacy as a medical treatment for a broad range of illnesses. More than 200 active ingredients have already been identified, but until now, there had been no way to tailor strains to produce certain cannabis substances or to alter the ratio between them.
A younger generation of researchers at the lab of Prof. Alexander (Sasha) Vainstein at the Hebrew University of Jerusalem’s Robert H. Smith Faculty of Agriculture, Food and Environment in Rehovot – in partnership with and funding from Mariana Bioscience Ltd. near Rehovot – have now successfully engineered a cannabis plant with higher levels of medically important substances such as THC.
The researchers successfully increased the level of THC by almost 17%, and the level of CBG, often referred to as “the mother of all cannabinoids,” by close to 25%. Now Vainstein and his team were able to increase the ratio of terpenes, which are responsible for maximizing the euphoric effects of cannabis by 20% to 30%.
The stated goal of their study was to find a way to intervene in the biochemical pathways in the cannabis plant to increase or decrease the production of active substances. The researchers accomplished this by manipulating a plant-based virus that had first been neutralized. In that way, it could not harm the plant. They then manipulated it to express the genes that influence the production of active substances in the cannabis plant.
“This represents an innovative use of these tools, which were constructed using synthetic biology tools,” explained Vainstein. “Next, we developed an innovative technology based on infection with an engineered virus to facilitate chemical reactions that increase the quantities of desired substances. In collaboration with Mariana Bioscience Ltd., we examined the infected plants and found that the levels of the substances in question had indeed risen.”
This is the first time that researchers have succeeded in performing such a feat with cannabis plants.
“These study results will be valuable both to industry, to increase the yield of active substances, and to medical researchers to cultivate and develop new strains for medical cannabis users,” said Vainstein. He added that more extensive experiments with the engineered plant are currently underway and should be available to cannabis industry leaders and medical research in the next few months.
Purchasing medical cannabis
Meanwhile, safety authorities have been concerned that the 100,000 Israelis who have Health Ministry licenses to purchase medical cannabis in various forms, including CBD compounds, could be at higher risk for being involved in road accidents because it could influence judgment. An Australian study, however, has found that even very high doses of up to 1,500 milligrams of CBD don’t affect driving.
Published in the Journal of Psychopharmacology, the University of Sydney study asked people to perform simulated driving tasks after consuming either a placebo or large amounts of CBD in oil form.
Unlike THC, CBD does not appear to intoxicate people. Instead, it has been reported to have calming and pain-relieving effects. The team did, however, add that their study looked at CBD in isolation only and that drivers taking CBD with other medications should do so with care.