Imagine a single plant that could make substances usually found in trees, mushrooms, and even toads — all at once. That's exactly what scientists at the Weizmann Institute of Science in Israel have created, and it could someday help researchers study how these substances might help treat mental health conditions.
The team, led by Dr. Paula (Shirley) Berman, engineered a type of tobacco plant to produce five well-known psychedelic compounds. In nature, these five compounds come from completely different living things scattered across the tree of life. One comes from a woody Amazon shrub in the coffee family. Two come from "magic mushrooms" — the same fungi once used in Aztec ceremonies. Another comes from a Sonoran Desert toad, which has special glands on its skin that release a milky liquid when threatened. The last comes from both the toad and certain plants.
"In effect, we created a kind of biological 'cocktail' — not by mixing substances externally, but by combining the underlying pathways inside one organism," explained Prof. Asaph Aharoni of Weizmann's Plant and Environmental Sciences Department.
The scientists first had to figure out exactly how plants naturally make DMT — the brain-active ingredient in ayahuasca, a hallucinogenic brew used in spiritual ceremonies in the Amazon for centuries. Though researchers knew DMT existed in nature, they didn't know which specific genes and proteins plants used to create it. Berman's team identified those missing pieces, then inserted the genes into a tobacco relative called Nicotiana benthamiana, a plant commonly used in scientific research. Within days, the engineered plant started producing DMT.
But one compound — 5-MeO-DMT from the Sonoran Desert toad — was only made in tiny amounts. So the team worked with protein-design experts Prof. Sarel Fleishman and Dr. Olga Khersonsky to fix the problem. They discovered that one molecule wasn't fitting properly into a key enzyme. By changing just a single building block in that enzyme, production jumped dramatically. "We mutated one amino acid in the sequence and got a 40-fold increase in the production of 5-MeO-DMT," Berman said.
The study, published in Science Advances, could eventually allow researchers to produce multiple psychedelic compounds in one place — without relying on rare plants, hard-to-collect fungi, or toads. That could make these substances easier to study for potential uses in mental health treatment.