Weizmann Institute of Science scientists revealed that a botanical relative of lettuce produces no less than 40 cannabinoids - active substances with medical potential that characterize the cannabis plant
A South African plant used in tribal ceremonies and known loosely as "woolly umbrella" produces a host of active substances (cannabinoids) identified with cannabis, although it is not a botanical relative of the famous green plant. in research the published in the scientific journal Nature Plants, Weizmann Institute of Science scientists identified that the plant with the umbrella-like yellow-velvety blossoms produces dozens of cannabinoids, some of which may have medicinal uses. The scientists even revealed the production processes of these substances in the plant and showed that they can be reproduced in the laboratory to create known cannabinoids and even engineer new ones.
"We found a new source of cannabinoids and developed tools that allow us to produce them in the laboratory and explore their enormous medical potential," says Dr. Shirley (Paula) Berman, who led the research in Prof. Assaf Aharoni in the plant and environmental sciences department of the institute. Even after the surprising discovery - the cannabis plant maintains its preeminence with more than 100 cannabinoids coming out of its plant and named after it. However, the woolly umbrella - a fast-growing relative of sunflower, lettuce and the blood of the Maccabees - certainly blows its neck with more than 40 cannabinoids, most of which were not known at all until now.
Already today, cannabinoids are widely used to relieve pain, nausea, anxiety and epileptic attacks, and it seems that the list of their medical indications is only growing. The medical promise contained in these materials led Prof. Aharoni's laboratory to go down to the roots of the woolly umbrella, or in its scientific name Helichrysum umbraculigerum. It has been known for many decades that in tribes in South Africa it is customary to put this plant on fire for ritual purposes or in healing ceremonies - possible evidence that the fire's fumes have a psychoactive effect. Indeed, more than 40 years ago, German scientists found preliminary evidence that the plant contains cannabinoids, but these findings have not yet been replicated in more recent studies.
Now in the new study, Dr. Berman and her colleagues confirmed these findings using a wide range of cutting-edge technologies: sequencing the genome of the woolly umbrella and using tools from the field of advanced analytical chemistry, including high-resolution mass spectroscopy, to identify which cannabinoids are encoded in it. The scientists also used nuclear magnetic resonance (NMR) to reveal the exact structure of more than ten of the cannabinoids as well as other related substances. And finally, uncover the full biochemical pathway of cannabinoid production in the plant, and identify where the production process takes place.
"The fact that during evolution, two plants that are not at all genetically related to each other developed the ability to produce cannabinoids, indicates that these substances have important ecological roles"
Unlike cannabis, which produces these substances in its short-lived flowers, the woolly umbrella produces the cannabinoids mainly in its perennial leaves - a fact that may give it an economic advantage over cannabis. Despite this significant difference, there is much in common between the plants when it comes to the production process: the scientists discovered that the enzymes involved in the production of cannabinoids in both cases belong to the same families - at least throughout the first half of the production process.
Six of the cannabinoids found in the woolly umbrella are the same as those in cannabis, but they do not include two of the most famous substances: THC and CBD. However, they do include CBG, a rising star in the cannabinoid sky thanks to its medical potential and lack of psychoactive effects. In addition, the acid version of CBG, which is found in the plant in a relatively high concentration, is a starting material for all classical cannabinoids - a finding that further strengthens the promise inherent in the plant as a valuable future source of cannabinoids.
To date, the roles of cannabinoids in plants have not been discovered, but the hypothesis is that they protect them from animals or other environmental hazards. "The fact that during evolution, two plants that are not at all genetically related to each other developed the ability to produce cannabinoids, indicates that these substances have important ecological roles," emphasizes Prof. Aharoni. "Further research will be required to find out what those roles are."
The researchers were not satisfied with mapping the production process of the cannabinoids in the plant and tried to produce cannabinoids themselves in the laboratory: for this purpose, they first produced the new enzymes discovered in the research on the leaves of the tobacco plant, and then used these enzymes to produce the cannabinoids themselves in yeast cells. Demonstrating the feasibility of these production capabilities marks a new way to produce cannabinoids for both research and applied purposes. Moreover, in the future it may be possible to use these methods to engineer new cannabinoids that do not exist in nature, for medicinal purposes.
In fact, the newly discovered cannabinoids may also lead to new healing possibilities. Dr. Berman says: "The next exciting step will be to characterize the properties of the more than 30 new cannabinoids we discovered in the plant, and see what medical uses they may have."
Dr. Berman led the research together with three other postdoctoral researchers in Prof. Aharoni's laboratory: Dr. Luis Alejandro de Haro, Dr. Adam Jozbiak and Dr. Prashant D. Sonavan. Also participating in the study were Dr. Shantan Panda, Zoe Pankas-Fazi, Dr. Yonghui Dong, Dr. Yelena Tsvatitsanin, Rotem Livna, Dr. Sagit Meir and Dr. Ilana Rogachev from Prof. Aharoni's laboratory; Ranjit Barbul of CSIR National Chemical Laboratory in Pune, India; Dr. Tali Sharaf, Dr. Eyal Shimoni, Dr. Samdar Zidman and Dr. Nili Dzorla from the Department of Chemical Research Infrastructures of the Institute, and Dr. Ekaterina Kopitman from the Department of Life Sciences Research Infrastructures of the Institute.
