By Pesach Benson • July 6, 2026
Jerusalem, 6 July, 2026 (TPS-IL) — Long before psychedelics entered modern laboratories, humans extracted mind-altering compounds from plants, mushrooms, and even animals for religious rituals and traditional medicine. Now, Israeli researchers say they have taken a major step toward producing several of these substances inside engineered plants. The work points to a future in which powerful psychoactive compounds — and potentially new drug candidates — could be manufactured in controlled biological systems rather than harvested from fragile or rare natural sources.
Psychedelic compounds such as DMT, 5-MeO-DMT, and related substances are not approved for routine medical use, but they are being studied experimentally for their potential in treating conditions including depression, anxiety, post-traumatic stress disorder (PTSD), and substance use disorders. Outside of clinical research, they are used primarily in traditional or ritual contexts, particularly ayahuasca ceremonies in parts of South America.
The research was conducted through a collaboration centered at the Weizmann Institute, where scientists engineered a tobacco-relative plant to produce five psychoactive compounds. The work was led in collaboration with Dr. Shirley (Paula) Berman of the Volcani Institute and builds on years of research mapping how these substances are formed in nature.
“At the heart of the research was the question of how DMT is produced in plants,” said Weizmann Institute Prof. Assaf Aharoni, in whose lab the research took place.
The breakthrough began with the full identification of the genes and enzymes responsible for DMT (dimethyltryptamine, a naturally occurring psychedelic compound found in plants and used in ayahuasca preparations) production, a key ingredient in ayahuasca. While the general biosynthetic pathway was previously known, the precise genetic instructions had not been fully mapped. After decoding the pathway, the researchers transferred it into a laboratory plant and demonstrated successful production of the compound.
Multiple Psychoactive Compounds
The team then expanded the system to include four additional psychoactive compounds originating from fungi and animals, ultimately combining all five production pathways within a single organism — an arrangement not observed in nature.
One of the most notable findings involved improving production of 5-MeO-DMT (a related psychoactive compound found in certain toad secretions), which initially appeared only in trace amounts. By modifying a single amino acid in a key enzyme, the team significantly increased efficiency. “We changed one amino acid in the protein sequence, and we got a 40-fold increase in the production of 5-MeO-DMT,” said Berman.
Once all five pathways were combined, the plant functioned as a living biochemical system capable of producing compounds associated with plants, fungi, and animals simultaneously. “We essentially created a kind of biological cocktail,” Aharoni said, “not by mixing substances from outside, but by combining their production pathways within a single organism.”
However, the system also revealed a key limitation. Because all pathways rely on the same precursor molecule derived from tryptophan (an amino acid used by plants as a building block for proteins and other biochemical compounds), they compete for resources inside the plant. This metabolic bottleneck reduced overall efficiency and highlights a central challenge in engineering more complex biological systems.
The researchers also introduced bacterial enzymes that enabled the plant to produce modified versions of these compounds, including chlorinated and brominated variants not found in nature. Some of these synthetic molecules have shown early biological activity in laboratory settings that may be relevant to potential antidepressant effects, although the findings remain preliminary.
The findings suggest a potential pathway toward reducing reliance on slow-growing plants, rare fungi, and animals such as the Sonoran desert toad, whose populations face harvest pressure linked to habitat loss and demand for its secretions. The work also raises broader scientific questions about the role of psychedelics in nature, including whether they function as defense mechanisms or signaling compounds.
While the research remains at an early stage and is not intended for immediate medical use, scientists say it opens new possibilities for drug discovery and the scalable production of complex natural compounds. Engineered plants could one day serve as engineered biological systems for producing difficult-to-obtain substances used in laboratory research, while also enabling the creation of novel “new-to-nature” compounds with potential therapeutic properties.
Before any pharmaceutical applications are considered, significant challenges remain, the scientists said, including scaling production, ensuring long-term genetic stability, and meeting regulatory requirements for medical development.
The study was published in the peer-reviewed Science Advances.
