A South African plant called a “woolly umbrella” is completely unrelated to the cannabis plant, but it produces dozens of the active compounds found in cannabis – cannabinoids – including some that may have new medical uses.
In a study published today in the prestigious journal Nature Plants, researchers at the Weizmann Institute of Science in Rehovot identified more than 40 cannabinoids in the woolly umbrella. The team revealed the series of biochemical steps the plant takes when it makes these compounds and also showed how these steps can be reproduced in the lab to synthesize or even engineer new cannabinoids.
Known to botanists, as Helichrysum umbraculigerum, the woolly umbrella is a tufted perennial herb that can reach one meter in height and is popular for making a garden border. The young parts are gray and thinly woolly, velvety and leafy, and the golden yellow flowers grow in clusters webbed together with “wool,” forming a parasol-like structure between January and April.
The familiar cannabis plant makes more than 100 different cannabinoids, and it remains their iconic producer. But the woolly umbrella – which grows very fast – is a respectable runner-up. “We have found a major new source of cannabinoids and developed tools for their sustained production that can help explore their enormous therapeutic potential,” said Dr. Shirley (Paula) Berman, who led the study in Prof. Asaph Aharoni’s lab in Weizmann’s plant and environmental sciences department.
Cannabinoids used for medical purposes
Cannabinoids are already widely applied to relieve pain, nausea, anxiety and epileptic seizures, and the list of their possible uses is quickly growing. Molecular receptors that respond to these compounds are common in humans, not only in the brain but also throughout the body; this suggests that the cannabinoids that bind to them might be used to treat everything from cancer to neurodegenerative diseases.
The promise that cannabinoids hold for medicine is precisely why Aharoni’s lab launched a study of the woolly umbrella. Its relatives include sunflowers, daisies and lettuce. But woolly umbrella has long been known to be burned in folk rituals to release intoxicating fumes, which hinted that it might contain chemicals affecting the brain. In fact, German scientists who studied the plant more than four decades ago found evidence that it contains cannabinoids, but more modern studies failed to reproduce their findings.
Now Berman and colleagues, using a battery of state-of-the-art technologies, confirmed that early report. They sequenced the entire genome of the woolly umbrella and used advanced analytical chemistry, including high-resolution mass spectroscopy, to identify the kinds of cannabinoids it contains. Using nuclear magnetic resonance, the researchers revealed the precise structure of more than a dozen of these cannabinoids and other related metabolites. They traced the entire biochemical pathway involved in the production of cannabinoids and determined where in the plant they are made.
It turns out that the woolly umbrella manufactures cannabinoids primarily in its leaves, possibly giving it an economic advantage over cannabis, which makes these compounds in the shorter-lived and harder-to-harvest flower clusters (inflorescences categorized on the basis of the arrangement of flowers on a main axis (and by the timing of its flowering). Despite this difference, the Weizmann scientists found a great deal in common between the woolly umbrella and cannabis. In particular, the enzymes used in every step of their cannabinoid production process belong to the same families throughout the first half of the biochemical pathway.
Six of the cannabinoids found in the woolly umbrella are identical to those in cannabis. The six do not include the two most famous ones, THC and CBD, but they do include cannabigerol (CBG), a rising star of cannabinoid research: It has potential therapeutic applications but lacks mood-altering effects. The acid form of CBG, which appears in a relatively high concentration in the plant, serves as a precursor for the production of all the classical cannabinoids. This supports the idea that the woolly umbrella could become a valuable source of plant-based cannabinoids.
What purpose cannabinoids serve in plants is unknown, but they probably provide defenses against animals or environmental hazards. “The fact that in the course of evolution, two genetically unrelated plants independently developed the ability to make cannabinoids suggests that these compounds perform important ecological functions,” Aharoni suggested. “More research is needed to determine what these functions are.”
His team has already taken their latest insights into cannabinoid genetics a step further, using them to generate the newly discovered cannabinoid-making enzymes in tobacco plants. The researchers also managed to use these enzymes to create finished cannabinoids in yeast, pointing to a new way of manufacturing the compounds for research and the biotech industry.
In the future, the study’s findings might even lead to engineering cannabinoids that don’t exist in nature. These could be designed to better bind to the human forms of the cannabinoid receptors, for example, or to achieve specific therapeutic benefits.
The cannabinoids naturally occurring in the woolly umbrella might also open up new possibilities. “The next exciting step would be to determine the properties of the more than 30 new cannabinoids we’ve discovered, and then to see what therapeutic uses they might have,” Berman concluded.