Scientists Engineer Plant to Produce Multiple Psychedelic Compounds

Scientists at the Weizmann Institute of Science have made a groundbreaking advancement in synthetic biology by engineering a fast-growing plant relative of tobacco to produce five distinct psychedelic compounds. The research, published in the journal *Science Advances*, showcases an innovative approach that integrates biochemical pathways from different kingdoms of life into a single organism.

The engineered plant, *Nicotiana benthamiana*, now serves as a "factory" for DMT, psilocybin, psilocin, bufotenin, and 5-MeO-DMT. Traditionally, these compounds are sourced from diverse natural sources such as the Amazonian shrub *Psychotria viridis*, various fungi species, and the skin glands of desert toads. The extraction process is laborious and time-consuming due to the scarcity and complexity involved in isolating each compound.

The interdisciplinary research team led by Dr. Paula Berman and Prof. Asaph Aharoni focused on understanding the genetic basis for these compounds' production. They identified key genes responsible for synthesizing DMT from the Amazonian shrub *Psychotria viridis* and an Australian acacia species, successfully introducing them into *Nicotiana benthamiana*. This process allowed the plant to start producing DMT within days of genetic modification.

The team then tackled the challenge of producing other compounds by applying a similar gene transfer technique. However, they encountered limitations with 5-MeO-DMT production. By collaborating with protein-design specialists Prof. Sarel Fleishman and Dr. Olga Khersonsky, they discovered that modifying just one amino acid in an enzyme's active site could significantly enhance the plant’s ability to produce this compound.

The significance of this achievement lies not only in its technical innovation but also in its potential applications for medical research and therapeutic use. Psychedelics like DMT, psilocybin, and others have shown promise in treating mental health conditions such as depression and anxiety when used under clinical supervision. The ability to produce these compounds efficiently through genetically modified plants could greatly enhance the accessibility of psychedelic-assisted therapies.

Moreover, this breakthrough underscores the interconnectedness of biochemical pathways across different kingdoms of life. All five compounds share a common chemical ancestor: tryptophan, an amino acid present in all living organisms. This shared chemistry facilitated the team's efforts to identify and introduce the necessary genes into *Nicotiana benthamiana*, enabling it to produce these complex molecules.

The Weizmann Institute’s research opens new avenues for exploring the therapeutic potential of psychedelic compounds while addressing practical challenges associated with their natural extraction methods. As scientists continue to investigate the benefits and risks of psychedelics in clinical settings, advancements like this could play a crucial role in making such treatments more widely available and accessible.