A chemical found in liverwort has surprising similarities to the THC in marijuana

By Noga Tarnopolsky

Oct. 26, 2018 9:20 AM PT

Reporting from Geneva — It’s an “amazing plant” that produces “hypnotic effects,” according to online testimonials. Some people who have ingested it or inhaled its smoke say it gave them a mild, marijuana-like high.

Now scientists have weighed in. In experiments with more than 100 mice, they found that chemicals in the liverwort plant produced four of the same key effects as THC, the primary psychoactive ingredient in marijuana.

An hour after being injected with the experimental chemicals, the mice entered a trance-like state, lost some of their ability to move, became less responsive to pain and experienced a drop in body temperature, according to a study published this week in the journal Science Advances.

The compounds were only “moderately potent,” the scientists reported, so they don’t expect liverwort to threaten marijuana’s popularity as a recreational drug.

But that relative weakness may actually be its strength. Because the liverwort chemicals provide some of the same biological benefits as THC with fewer psychoactive side effects, it has the potential to be more useful as a medicine, the study authors said.

THC, or tetrahydrocannabinol, was first isolated and synthesized in 1964 by Israeli organic chemist Raphael Mechoulam. That paved the way for scientists to investigate the way canabinnoids interact with the human body and led to Mechoulam’s discovery that the brain produces its own cannabinoid compound. He named it anandamide, after ananda, the Sanskrit word for bliss.

Thirty years later, in 1994, the Japanese phytochemist Yoshinori Asakawa identified a related substance in the liverwort plant Radula perrottetii. He called it perrottetinene, or PET, and it was later found in two other species of liverwort.

The researchers who conduced the new study say they are the first to study PET’s structure and effect.

When they gave the PET compounds to the mice, they observed several familiar behaviors. The animals had trouble keeping their balance on a slowly rotating rod (the rodent equivalent of a treadmill machine). They did not register pain right away after being placed on a hot plate. And when their front limbs were propped up on a bar, they did not immediately readjust to a more comfortable position.

In other experiments, the researchers tested PET to see what it would do in the brain. They found that the compounds acted on some of the same cannabinoid receptors at THC. But the researchers were surprised to find that unlike THC, PET reduced the level of chemicals called prostaglandins that can cause harmful inflammation.

To Jürg Gertsch, a neuroscientist at the University of Bern in Switzerland and the study’s senior author, the most notable result of the work is that PET “differs from THC in a way that could be much less problematic in terms of adverse central effects.”

Mechoulam, who was not involved in the study, agreed. The discovery of a new alternative to THC “opens wide the possibilities for novel drugs,” he said.

But that doesn’t mean it will be easy. This species of liverwort only grows in Japan, New Zealand and Costa Rica, and Gertsch acknowledged that cultivating it may “may be challenging” because it reproduces without seeds.

Gertsch said he was astonished to realize that “nature produces psychoactive cannabinoids in only two species of plant, separated by 300 million years of evolution.”

He added that the pharmaceutical promise of PET may raise the profile of bryophytes, the unsung group of plants that includes liverworts and mosses. To date, he said, they have been “a bit neglected in terms of bioprospecting,” the term for research into organisms that may have medicinal value.

“The fact that liverworts can generate natural products relevant to humans is a great example” of the importance of the field, he said.

Tarnopolsky is a special correspondent.