A South African plant called “woolly umbrella” is entirely separate from the cannabis plant, but it produces dozens of the active compounds found in cannabis – cannabinoids – including some that could have new medicinal 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 wool umbrella. The team unveiled the series of biochemical steps the plant takes when making these compounds, and also showed how these steps can be reproduced in the laboratory to synthesize or even make new cannabinoids.
Known to botanists as Strawflower umbraculigerum, the Wool Umbrella is a tufted perennial that can grow up to a meter tall and is often used as a garden border. The young parts are gray and thinly woolly, velvety and leafy, and the golden-yellow flowers grow in clusters associated with ‘wool’, forming a parasol-like structure between January and April.
The well-known cannabis plant produces more than 100 different cannabinoids and remains its iconic producer. But the woolly umbrella – which grows very quickly – is a respectable runner-up. “We have found an important new source of cannabinoids and developed tools for their sustainable production that can help explore their enormous therapeutic potential,” said Dr. Shirley (Paula) Berman, who led the study in Prof. Asaph Aharoni’s laboratory at Weizmann’s plant and Department of Environmental Sciences.
cannabinoids for medical purposes
Cannabinoids are already widely used to relieve pain, nausea, anxiety, and epileptic seizures, and the list of possible uses is growing fast. In humans, molecular receptors that respond to these compounds are not only distributed in the brain but also throughout the body; This suggests that the cannabinoids that bind to them could be used to treat everything from cancer to neurodegenerative diseases.
The promise that cannabinoids hold for medicine is exactly why Aharoni’s lab started a study on the wool umbrella. Its relatives include sunflowers, daisies, and lettuce. However, wool umbrellas have long been known to be burned in folk rituals to release intoxicating fumes, suggesting they may contain brain-affecting chemicals. In fact, German scientists studying the plant more than four decades ago found evidence that it contained cannabinoids, but more modern studies have failed to reproduce their findings.
Now, Berman and colleagues have corroborated that early report using a battery of cutting-edge technologies. They sequenced the entire genome of the wool umbrella and used advanced analytical chemistry, including high-resolution mass spectroscopy, to identify the cannabinoids it contained. 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 woolly umbrella manufactures cannabinoids mainly in its leaves, potentially giving it an economic advantage over cannabis, producing these compounds in the shorter-lived and harder-to-harvest flower clusters (inflorescences categorized based on the arrangement of flowers along a major axis ( and by the timing of their flowering). Despite this difference, the Weizmann scientists found many similarities between the wool umbrella and cannabis, particularly the enzymes used in each step of their cannabinoid production process, which belong to the same families during the first half of the biochemical pathway.
Six of the cannabinoids found in the wool umbrella are identical to those found in cannabis. The six don’t contain the two most famous THC and CBD, but cannabigerol (CBG), a rising star in cannabinoid research: it has potential therapeutic uses but no mood-altering effects. The acid form of CBG, which is found in relatively high concentrations in the plant, serves as a precursor to the production of all classic cannabinoids. This supports the idea that the wool umbrella could become a valuable source of plant-based cannabinoids.
The purpose of cannabinoids in plants is unknown, but they likely provide defenses against animals or environmental threats. “The fact that two genetically unrelated plants independently evolved the ability to produce cannabinoids suggests that these compounds serve important ecological functions,” Aharoni suggested. “Further research is needed to determine what these functions are.”
His team has already taken their latest findings on cannabinoid genetics one step further and used them to generate the newly discovered cannabinoid-forming enzymes in tobacco plants. The researchers also managed to use these enzymes to make finished cannabinoids in yeast, indicating a new way of making the compounds for research and the biotech industry.
In the future, the results of the study could even lead to engineered cannabinoids not found in nature. For example, these could be designed to bind better to the human forms of the cannabinoid receptors or achieve specific therapeutic benefits.
The cannabinoids naturally occurring in the wool umbrella could also open up new possibilities. “The next exciting step would be to determine the properties of the more than 30 new cannabinoids we have discovered and then see what therapeutic benefits they might have,” concluded Berman.
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