Researchers at Israel’s Weizmann Institute of Science report engineering a single tobacco plant to produce five tryptophan-derived compounds, including the psychedelics psilocybin and DMT. The work, led by Prof. Asaph Aharoni and Dr. Shirley (Paula) Berman, reconstructed biosynthetic pathways drawn from mushrooms, plants, and toads into one host organism. The achievement opens a potential route to scalable, lab-grown psychedelics at a time when clinical interest in these substances for mental health treatment is accelerating.
Five Compounds, Three Kingdoms, One Plant
The team’s central accomplishment was assembling complete biosynthetic pathways for five natural psychedelics and expressing them in Nicotiana benthamiana, a species of tobacco widely used as a workhorse in plant biotechnology. The five compounds the team reports detecting are psilocybin, DMT (N,N-dimethyltryptamine), 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), bufotenin, and 5-HTP (5-hydroxytryptophan), a biochemical precursor rather than a psychedelic. Each originates in a different biological source: psilocybin and psilocin come from fungi, DMT from traditional hallucinogenic plant species, and 5-MeO-DMT and bufotenin are associated with toad secretions. The study drew genetic instructions from multiple organisms and reconstructed full biosynthetic pathways inside a single plant assay, a result the authors describe as a first for this specific kind of multi-compound pathway reconstruction in a single plant host.
A critical first step was elucidating the complete DMT biosynthetic pathway from traditional hallucinogenic plant species, which had remained only partially characterized. With that pathway mapped, the researchers could combine it with fungal psilocybin genes and toad-derived tryptamine modification enzymes in the same tobacco chassis. The underlying sequencing effort was substantial: 49 SRA experiments are associated with the project, reflecting the breadth of species, tissues, and conditions the team analyzed to identify and validate each enzymatic step.
The peer-reviewed description of this work in Science Advances details how the researchers introduced and expressed multiple gene cassettes in tobacco and verified that each pathway was functional. Using analytical chemistry tools, they confirmed the presence of all five target compounds in plant tissues, showing that the reconstructed pathways were not only present but also active. The authors write that this is the first report of a single plant host simultaneously producing this diverse a panel of tryptophan-derived compounds, including several tryptamine-based psychedelics.
Why Tobacco Works as a Drug Factory
Choosing tobacco was not arbitrary. Nicotiana species already produce tryptophan-derived specialized metabolites through their own native biochemistry, which means the cellular machinery needed to supply precursor molecules is already running. Peer-reviewed research on plant aromatic amino acid decarboxylases has shown that Nicotiana can serve as an effective chassis host for engineering tryptamine-based compounds. In practical terms, the plant’s existing metabolic infrastructure reduces the number of foreign genes that need to be introduced and lowers the risk of bottlenecks where precursor supply runs dry.
The Weizmann team has a track record in this area. Earlier work from Prof. Aharoni’s lab demonstrated the institute’s capability in mapping complex natural-product pathways and transferring biosynthetic enzymes into tobacco and yeast. That prior research, published in Nature Plants, laid the groundwork for the current, more ambitious project by proving that multi-step enzymatic cascades could function reliably in a plant host. The new study extends that logic from single pathways to an entire panel of related but distinct psychedelic molecules, testing how far plant metabolic engineering can be pushed before it runs into systemic limits.
Beyond metabolic compatibility, tobacco brings practical advantages. Nicotiana benthamiana grows quickly, is amenable to both transient and stable genetic transformation, and is already used at industrial scale to produce vaccines and biologic drugs. That existing infrastructure could, in principle, be adapted to produce psychedelic compounds, lowering barriers to commercialization if yields prove sufficient.
A Toad-Free Alternative
One of the most immediate practical implications concerns 5-MeO-DMT and bufotenin, two compounds traditionally sourced from the secretions of Incilius alvarius, the Sonoran Desert toad. Harvesting these secretions raises serious ecological and ethical concerns. Conservation advocates and researchers have raised concerns that wild populations face pressure from habitat loss and from collectors seeking the psychoactive venom, and studies documenting these tryptamines in Incilius alvarius secretions have helped frame the case for synthetic or biosynthetic alternatives.
Separate research has explored cell-based synthesis approaches for 5-MeO-DMT and related molecules, using engineered microbial or mammalian systems to replicate the toad’s chemistry. While promising, those systems can be technically complex and expensive to scale. Producing the same compounds inside a fast-growing plant could offer a simpler and potentially more sustainable path to industrial volumes, especially for applications where ultra-high purity and consistent dosing are essential.
The plant-based method sidesteps both wild harvesting and the complexity of amphibian cell culture. If yields can be optimized, tobacco fields or greenhouse operations could supply pharmaceutical-grade 5-MeO-DMT and bufotenin without any toad involvement. That distinction matters not only for conservation but also for regulatory consistency: a defined, reproducible plant-based production system is far easier to standardize than a supply chain dependent on animal secretions of variable composition. For companies seeking to develop psychedelic-assisted therapies, a toad-free source may also be more acceptable to patients and ethics committees.
What the Study Does Not Yet Prove
Coverage of this work has tended toward enthusiasm, but several gaps deserve attention. The publicly available records, including the peer-reviewed paper in Science Advances, confirm pathway reconstruction and compound detection. What they do not yet provide is detailed quantitative yield data showing that tobacco-produced psychedelics can match the concentrations needed for cost-effective pharmaceutical manufacturing. Demonstrating that an engineered plant can make a molecule is a different challenge from demonstrating that it can make enough of that molecule to compete with chemical synthesis or fermentation.
Metabolic bottlenecks in non-native hosts are a well-known problem in synthetic biology. When foreign enzymatic pathways are introduced into a plant, they compete with the host’s own metabolism for shared precursors like tryptophan and S-adenosylmethionine. The result is often lower-than-expected titers and accumulation of unwanted intermediates. Until the Weizmann team or independent groups publish yield optimization data, the commercial viability of this platform remains an open question rather than a demonstrated fact.
Another limitation is that the current work focuses on proof-of-concept production in laboratory conditions. Scaling up to field or greenhouse cultivation introduces additional variables: environmental stress, variable light conditions, and pathogen exposure can all influence metabolic flux and compound stability. Regulatory authorities would also require rigorous characterization of impurities and potential plant-derived contaminants before approving any therapeutic product made this way.
Implications for Psychedelic Medicine
Even with those caveats, the study arrives at a pivotal moment for psychedelic medicine. Clinical research is actively testing psilocybin and related compounds for conditions including treatment-resistant depression and other mental health indications. Reliable, scalable production methods are a prerequisite for moving from small clinical studies to widespread therapeutic use. A plant-based platform that can generate several different psychedelics in one organism could simplify supply chains for researchers and, eventually, drug manufacturers.
There are also scientific advantages to having multiple compounds produced in the same biological context. Researchers could, in principle, engineer plants that generate defined ratios of psilocybin, DMT, and 5-MeO-DMT, enabling studies on how these molecules interact or differ in their pharmacology. Such “polypharmaceutical” plants might help answer questions about whether combinations of psychedelics offer therapeutic benefits distinct from single-molecule treatments, while still allowing precise control over dose and composition.
At the same time, the work underscores broader trends in bioengineering: the convergence of genomics, synthetic biology, and plant science to reprogram familiar crops into high-value chemical factories. Tobacco, long associated with addiction and disease, is being repurposed as a chassis for vaccines, antibodies, and now psychedelics. How regulators, clinicians, and the public respond to that transformation will help determine whether these engineered plants move from the greenhouse bench to the clinic and, ultimately, to patients.
For now, the Weizmann study should be read as a striking demonstration of what is technically possible rather than as an immediate solution to the supply challenges of psychedelic medicine. It shows that complex biosynthetic pathways from fungi, plants, and toads can be combined and made to function in a single plant host. The next phase, optimizing yields, proving economic viability, and navigating regulatory pathways, will determine whether a tobacco plant that makes psilocybin and DMT becomes a scientific curiosity or a cornerstone of future psychedelic therapies.
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*This article was researched with the help of AI, with human editors creating the final content.
